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  • 1.
    Morin, Maxim
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Björklund, Sebastian
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Nilsson, Emelie J.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Bicontinuous Cubic Liquid Crystals as Potential Matrices for Non-Invasive Topical Sampling of Low-Molecular-Weight Biomarkers2023In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 15, no 8, article id 2031Article in journal (Refereed)
    Abstract [en]

    Many skin disorders, including cancer, have inflammatory components. The non-invasive detection of related biomarkers could therefore be highly valuable for both diagnosis and follow up on the effect of treatment. This study targets the extraction of tryptophan (Trp) and its metabolite kynurenine (Kyn), two compounds associated with several inflammatory skin disorders. We furthermore hypothesize that lipid-based bicontinuous cubic liquid crystals could be efficient extraction matrices. They comprise a large interfacial area separating interconnected polar and apolar domains, allowing them to accommodate solutes with various properties. We concluded, using the extensively studied GMO-water system as test-platform, that the hydrophilic Kyn and Trp favored the cubic phase over water and revealed a preference for locating at the lipid-water interface. The interfacial area per unit volume of the matrix, as well as the incorporation of ionic molecules at the lipid-water interface, can be used to optimize the extraction of solutes with specific physicochemical characteristics. We also observed that the cubic phases formed at rather extreme water activities (>0.9) and that wearing them resulted in efficient hydration and increased permeability of the skin. Evidently, bicontinuous cubic liquid crystals constitute a promising and versatile platform for non-invasive extraction of biomarkers through skin, as well as for transdermal drug delivery.

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  • 2.
    Morin, Maxim
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Runnsjö, Anna
    Zelmic AB, Lund, Sweden.
    Ruzgas, Tautgirdas
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Björklund, Sebastian
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Effects of storage conditions on permeability and electrical impedance properties of the skin barrier.2023In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 637, p. 122891-, article id 122891Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the effect of various skin preservation protocols on in vitro drug permeation, epidermal-dermal drug distribution, and electrical impedance properties of skin membranes. Acyclovir (AC) and methyl salicylate (MS) were selected as model drugs due to their different physicochemical properties and skin metabolic profiles. In particular, AC is relatively hydrophilic (logP -1.8) and not expected to be affected by skin metabolism, while MS is relatively lipophilic (logP 2.5) and susceptible to metabolism, being a substrate for esterase residing in skin. Skin from pig ears was used and freshly excised into split-thickness membranes, which were divided and immediately stored at five different storage conditions: a) 4 °C overnight (fresh control), b) 4 °C for 4 days, c) and d) -20 °C for 6 weeks and one year, respectively, and e) -80 °C for 6 weeks. Based on the combined results, general trends are observed showing that fresh skin is associated with lower permeation of both model drugs and higher skin membrane electrical resistance, as compared to the other storage conditions. Interestingly, in the case of fresh skin, significantly lower amounts of MS are detected in the epidermis and dermis compartments, implying higher levels of ester hydrolysis of MS (i.e., higher esterase activity). In line with this, the concentration of salicylic acid (SA) extracted from the dermis is significantly higher for fresh skin, as compared to the other storage conditions. Nevertheless, for all storage conditions, substantial amounts of SA are detected in the receptor medium, as well as in the epidermis and dermis, implying that esterase activity is maintained to some extent in all cases. For AC, which is not expected to be affected by skin metabolism, freeze storage (protocols c-e) is observed to result in higher accumulation of AC in the epidermis, as compared to the case of fresh skin, while the AC concentration in dermis is unaffected. These observations can be rationalized primarily by the observed lower permeability of fresh skin towards this hydrophilic substance. Finally, a strong correlation between AC permeation and electrical skin resistance is shown for individual skin membranes irrespective of storage condition, while the corresponding correlation for MS is inferior. On the other hand, a strong correlation is shown for individual membranes between MS permeation and electrical skin capacitance, while a similar correlation for AC is lower. The observed correlations between drug permeability and electrical impedance open up for standardizing in vitro data for improved analysis and comparisons between permeability results obtained with skin stored at different conditions.

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  • 3.
    Stenqvist, Björn
    et al.
    Division of Physical Chemistry, Department of Chemistry, Lund University, POB 124, SE-221 00 Lund, Sweden.
    Ericson, Marica B.
    Biomedical Photonics Group, Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96 Gothenburg, Sweden.
    Gregoire, Sebastien
    L’Oreal Research & Innovation, 1, avenue Eugène Schueller, 93601 Aulnay-sous-Bois, France.
    Biatry, Bruno
    L’Oreal Research & Innovation, 1, avenue Eugène Schueller, 93601 Aulnay-sous-Bois, France.
    Cassin, Guillaume
    L’Oreal Research & Innovation, 1, avenue Eugène Schueller, 93601 Aulnay-sous-Bois, France.
    Jankunec, Marija
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. Institute of Biochemistry Life Sciences Center, Vilnius University, LT-10257 Vilnius, Lithuania.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Sparr, Emma
    Division of Physical Chemistry, Department of Chemistry, Lund University, POB 124, SE-221 00 Lund, Sweden.
    Membrane permeability based on mesh analysis2023In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 633, p. 526-535Article in journal (Refereed)
    Abstract [en]

    The main function of a membrane is to control the exchange of matter between the surrounding regions. As such, accurate modeling of membranes is important to properly describe their properties. In many cases in both biological systems and technical applications, the membranes are composite structures where transport properties may vary between the different sub-regions of the membrane. In this work we develop a method based on Mesh analysis that is asymptotically exact and can describe diffusion in composite membrane structures. We do this by first reformulating a generalized Fick’s law to include the effects from activity coefficient, diffusion coefficient, and solubility using a single condensed parameter. We then use the derived theory and Mesh analysis to, in essence, retrieve a finite element method approach. The calculated examples are based on a membrane structure that reassembles that of the brick and mortar structure of stratum corneum, the upper layer of our skin. Resulting concentration profiles from this procedure are then compared to experimental results for the distribution of different probes within intact stratum corneum, showing good agreement. Based on the derived approach we further investigate the impact from a gradient in the fluidity of the stratum corneum mortar lipids across the membrane, and find that it is substantial. We also show that anisotropic organisation of the lipid mortar can have large impact on the effective permeability compared to isotropic mortar lipids. Finally, we examine the effects of corneocyte swelling, and their lateral arrangement in the membrane on the overall membrane permeability.

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  • 4.
    Morin, Maxim
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Jankovskaja, Skaidre
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Ruzgas, Tautgirdas
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Henricson, Joakim
    Linkoping Univ, Fac Hlth Sci, Dept Biomed & Clin Sci, Div Clin Chem & Pharmacol, S-58183 Linkoping, Sweden.;Local Hlth Care Serv Cent Ostergotland, Dept Emergency Med, S-58185 Linkoping, Sweden..
    Anderson, Chris D.
    Linkoping Univ, Fac Hlth Sci, Dept Biomed & Clin Sci, Div Cell Biol, S-58183 Linkoping, Sweden..
    Brinte, Anders
    ImaGene iT, Medicon Village, S-22363 Lund, Sweden..
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Björklund, Sebastian
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Hydrogels and Cubic Liquid Crystals for Non-Invasive Sampling of Low-Molecular-Weight Biomarkers-An Explorative In Vivo Study2022In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 14, no 2, article id 313Article in journal (Refereed)
    Abstract [en]

    The molecular composition of human skin is altered due to diseases, which can be utilized for non-invasive sampling of biomarkers and disease diagnostics. For this to succeed, it is crucial to identify a sampling formulation with high extraction efficiency and reproducibility. Highly hydrated skin is expected to be optimal for increased diffusion of low-molecular-weight biomarkers, enabling efficient extraction as well as enhanced reproducibility as full hydration represents a well-defined endpoint. Here, the aim was to explore water-based formulations with high water activities, ensuring satisfactory skin hydration, for non-invasive sampling of four analytes that may serve as potential biomarkers, namely tryptophan, tyrosine, phenylalanine, and kynurenine. The included formulations consisted of two hydrogels (chitosan and agarose) and two different liquid crystalline cubic phases based on the polar lipid glycerol monooleate, which were all topically applied for 2 h on 35 healthy subjects in vivo. The skin status of all sampling sites was assessed by electrical impedance spectroscopy and transepidermal water loss, enabling explorative correlations between biophysical properties and analyte abundancies. Taken together, all formulations resulted in the successful and reproducible collection of the investigated biomarkers. Still, the cubic phases had an extraction capacity that was approximately two times higher compared to the hydrogels.

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  • 5.
    Argatov, Ivan
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. Institut für Mechanik, Technische Universität Berlin, 10623 Berlin, Germany.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Kocherbitov, Vitaly
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Modeling of composite sorption isotherm for stratum corneum2022In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1864, no 7, p. 1-8, article id 183910Article in journal (Refereed)
    Abstract [en]

    Equilibrium water sorption in stratum corneum (SC) is considered by treating it as a biocomposite with two main phases, namely, corneocytes and lipids. To validate the rule of mixtures for the individual phase sorption isotherms, a new flexible fitting model is introduced by accounting for characteristic features observed in the variations of the thermodynamic correction factors corresponding to the individual sorption isotherms. The comparison of the model fitting performance with that of the five-parameter Park's model shows a remarkably good ability to fit experimental data for different types of sorption isotherms. The effect of the lipids content on the variance of the composite sorption isotherm of stratum corneum is highlighted. The sensitivity analysis reveals that for the typical water content 20-30 wt%, which corresponds to the SC in a stable condition, the sensitivity of the composite sorption isotherm to the variation of the lipids content on dry basis is predominantly positive and sufficiently small. The good agreement observed between the experimental sorption isotherm for SC and the composite isotherm, which is based on the rule of mixtures for the individual phase sorption isotherms, yields a plausible conclusion (hypothesis) that the corneocytes-lipids mechanical interaction during unconstrained swelling of the SC membrane in the in vitro laboratory experiment is negligible.

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  • 6.
    Jankovskaja, Skaidre
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Morin, Maxim
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Gustafsson, Anna
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Anderson, Chris D
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping 581 83, Sweden; Department of Dermatology and Venereology, Linköping 581 83, Sweden.
    Lehoczki, Boglarka
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Björklund, Sebastian
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Rezeli, Melinda
    Clinical Protein Science and Imaging, Department of Biomedical Engineering, Lund University, Lund 221 00, Sweden.
    Marko-Varga, György
    Clinical Protein Science and Imaging, Department of Biomedical Engineering, Lund University, Lund 221 00, Sweden.
    Ruzgas, Tautgirdas
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Non-Invasive, Topical Sampling of Potential, Low-Molecular Weight, Skin Cancer Biomarkers: A Study on Healthy Volunteers.2022In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 94, no 15, p. 5856-5865Article in journal (Refereed)
    Abstract [en]

    Monitoring of low-molecular weight cancer biomarkers, such as tryptophan (Trp) and its derivative kynurenine (Kyn), might be advantageous to non-invasive skin cancer detection. Thus, we assessed several approaches of topical sampling of Trp and Kyn, in relation to phenylalanine (Phe) and tyrosine (Tyr), on the volar forearm of six healthy volunteers. The sampling was performed with three hydrogels (made of agarose or/and chitosan), hydrated starch films, cotton swabs, and tape stripping. The biomarkers were successfully sampled by all approaches, but the amount of collected Kyn was low, 20 ± 10 pmol/cm2. Kyn quantification was below LOQ, and thus, it was detected only in 20% of topical samples. To mitigate variability problems of absolute amounts of sampled amino acids, Tyr/Trp, Phe/Trp, and Phe/Tyr ratios were assessed, proving reduced inter-individual variation from 79 to 45% and intra-individual variation from 42 to 21%. Strong positive correlation was found between Phe and Trp, pointing to the Phe/Trp ratio (being in the 1.0–2.0 range, at 95% confidence) being least dependent on sampling materials, approaches, and sweating. This study leads to conclusion that due to the difficulty in quantifying less abundant Kyn, and thus the Trp/Kyn ratio, the Phe/Trp ratio might be a possible, alternative biomarker for detecting skin cancers.

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  • 7.
    Valetti, Sabrina
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Riaz, Azra
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Doko, Anemona
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Sultana, Kaiser
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Eskandari, Mahboubeh
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Prgomet, Zdenka
    Malmö University, Faculty of Odontology (OD).
    Feiler, Adam
    Nanologica AB, 151 36 Södertälje, Sweden; Chemistry Department, KTH, Royal Institute of Technology, 100 44 Stockholm, Sweden.
    Rönn, Robert
    Orexo AB, 754 50 Uppsala, Sweden.
    Dahlström, Bengt
    CTC Clinical Trial Consultants AB, 75237 Uppsala, Sweden.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Björklund, Sebastian
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Oral transmucosal delivery of eletriptan for neurological diseases.2022In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 627, article id 122222Article in journal (Refereed)
    Abstract [en]

    Migraine is a highly prevalent neurological disease affecting circa 1 billion patients worldwide with severe incapacitating symptoms, which significantly diminishes the quality of life. As self-medication practice, oral administration of triptans is the most common option, despite its relatively slow therapeutic onset and low drug bioavailability. To overcome these issues, here we present, to the best of our knowledge, the first study on the possibility of oral transmucosal delivery of one of the safest triptans, namely eletriptan hydrobromide (EB). Based on a comprehensive set of in vitro and ex vivo experiments, we highlight the conditions required for oral transmucosal delivery, potentially giving rise to similar, or even higher, drug plasma concentrations expected from conventional oral administration. With histology and tissue integrity studies, we conclude that EB neither induces morphological changes nor impairs the integrity of the mucosal barrier following 4 h of exposure. On a cellular level, EB is internalized in human oral keratinocytes within the first 5 min without inducing toxicity at the relevant concentrations for transmucosal delivery. Considering that the pKa of EB falls within the physiologically range, we systematically investigated the effect of pH on both solubility and transmucosal permeation. When the pH is increased from 6.8 to 10.4, the drug solubility decreases drastically from 14.7 to 0.07 mg/mL. At pH 6.8, EB gave rise to the highest drug flux and total permeated amount across mucosa, while at pH 10.4 EB shows greater permeability coefficient and thus higher ratio of permeated drug versus applied drug. Permeation experiments with model membranes confirmed the pH dependent permeation profile of EB. The distribution of EB in different cellular compartments of keratinocytes is pH dependent. In brief, high drug ionization leads to higher association with the cell membrane, suggesting ionic interactions between EB and the phospholipid head groups. Moreover, we show that the chemical permeation enhancer DMSO can be used to enhance the drug permeation significantly (i.e., 12 to 36-fold increase). Taken together, this study presents important findings on transmucosal delivery of eletriptan via the oral cavity and paves the way for clinical investigations for a fast and safe migraine treatment.

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  • 8.
    Ali, Abdullah
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Speximo AB, Medicon Village, SE-223 81 Lund, Sweden.
    Skedung, L
    RISE Research Institutes of Sweden, Bioeconomy and Health, Perception and Design, Stockholm, Sweden.
    Burleigh, S
    Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden.
    Lavant, Eva
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Ringstad, L
    RISE Research Institutes of Sweden, Bioeconomy and Health, Perception and Design, Stockholm, Sweden.
    Andersson, CD
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Wahlgren, M
    Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Relationship between sensorial and physical characteristics of topical creams: a comparative study of effects of excipients2022In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 613, p. 1-12, article id 121370Article in journal (Refereed)
    Abstract [en]

    Rising consumer demands for safer, more natural, and sustainable topical products have led to increased interest in finding alternative excipients, while retaining functionality and cosmetic appeal. Particle-stabilized Pickering creams have emerged as possible alternatives to replace traditional surfactant-stabilized creams and are thus one of the focuses in this study. The aim of this paper was to study relationships between sensorial characteristics and physical properties to understand how different excipients affect these aspects, comparing one starch particle–stabilized and three surfactant-stabilized formulations. A human panel was used to evaluate sensorial perception, while physical properties were deduced by rheology and tactile friction, together with in vivo and ex vivo skin hydration measurements.

    The results show that sensorial attributes related to the application phase can be predicted with rheology, while afterfeel attributes can be predicted with tactile friction studies. Differences in rheological and sensory properties among surfactant-based creams could mainly be attributed to the type of emollients used, presence of thickeners and surfactant composition. Differences between surfactant-based creams and a Pickering cream were more evident in relation to the afterfeel perception. Presence of starch particles in the residual film on skin results in high tactile friction and low perception of residual coating, stickiness, greasiness, and slipperiness in sensorial afterfeel.

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  • 9.
    Kumlien, Christine
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Care Science (VV). Skane Univ Hosp, Dept Cardiothorac & Vasc Surg, Malmo, Sweden..
    Acosta, Stefan
    Skane Univ Hosp, Dept Cardiothorac & Vasc Surg, Malmo, Sweden.;Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Björklund, Sebastian
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Lavant, Eva
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Lazer, Victoria
    Malmö University, Faculty of Health and Society (HS), Department of Care Science (VV).
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Ruzgas, Tautgirdas
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Gershater, Magdalena
    Malmö University, Faculty of Health and Society (HS), Department of Care Science (VV).
    Research priorities to prevent and treat diabetic foot ulcers-A digital James Lind Alliance Priority Setting Partnership2022In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 39, no 11, article id e14947Article in journal (Refereed)
    Abstract [en]

    Aim To establish outcomes of a priority setting partnership between participants with diabetes mellitus and clinicians to identify the top 10 research priorities for preventing and treating diabetic foot ulcers (DFUs). Methods Due to the COVID-19 pandemic, the James Lind Alliance Priority Setting Partnership process was adapted into a digital format which involved a pilot survey to identify understandable uncertainties with high relevance for participants tested by calculating the content validity index; a main survey answered by 53 participants living with diabetes and 49 clinicians; and a final digital workshop to process and prioritise the final top 10 research priorities. Results The content validity index was satisfactory for 20 out of 25 uncertainties followed by minor changes and one additional uncertainty. After we processed the 26 uncertainties from the main survey and seven current guidelines, a list of 28 research uncertainties remained for review and discussion in the digital workshop. The final top 10 research priorities included the organisation of diabetes care; screening of diabetes, impaired blood circulation, neuropathy, and skin properties; vascular surgical treatment; importance of self-care; help from significant others; pressure relief; and prevention of infection. Conclusion The top 10 research priorities for preventing and treating DFUs represent consensus areas from persons living with diabetes and clinicians to guide future research. These research priorities can justify and inform strategic allocation of research funding. The digitalisation of James Lind Alliance methodology was feasible.

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  • 10.
    Morin, Maxim
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Björklund, Sebastian
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Jankovskaja, Skaidre
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Moore, Kieran
    Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England..
    Delgado-Charro, Maria Begona
    Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England..
    Ruzgas, Tautgirdas
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Guy, Richard H.
    Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England..
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Reverse Iontophoretic Extraction of Skin Cancer-Related Biomarkers2022In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 14, no 1, article id 79Article in journal (Refereed)
    Abstract [en]

    Non-invasive methods for early diagnosis of skin cancer are highly valued. One possible approach is to monitor relevant biomarkers such as tryptophan (Trp) and kynurenine (Kyn), on the skin surface. The primary aim of this in vitro investigation was, therefore, to examine whether reverse iontophoresis (RI) can enhance the extraction of Trp and Kyn, and to demonstrate how the Trp/Kyn ratio acquired from the skin surface reflects that in the epidermal tissue. The study also explored whether the pH of the receiver medium impacted on extraction efficiency, and assessed the suitability of a bicontinuous cubic liquid crystal as an alternative to a simple buffer solution for this purpose. RI substantially enhanced the extraction of Trp and Kyn, in particular towards the cathode. The Trp/Kyn ratio obtained on the surface matched that in the viable skin. Increasing the receiver solution pH from 4 to 9 improved extraction of both analytes, but did not significantly change the Trp/Kyn ratio. RI extraction of Trp and Kyn into the cubic liquid crystal was comparable to that achieved with simple aqueous receiver solutions. We conclude that RI offers a potential for non-invasive sampling of low-molecular weight biomarkers and further investigations in vivo are therefore warranted.

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  • 11.
    Ali, Abdullah
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. Speximo AB, Medicon Village, Lund.
    Ringstad, Lovisa
    RISE Research Institutes of Sweden, Bioeconomy and Health, Stockholm.
    Skedung, Lisa
    RISE Research Institutes of Sweden, Bioeconomy and Health, Stockholm.
    Falkman, Peter
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Wahlgren, Marie
    Food Technology, Engineering and Nutrition, Lund University.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Tactile friction of topical creams and emulsions: Friction measurements on excised skin and VitroSkin® using ForceBoard™.2022In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 615, article id 121502Article in journal (Refereed)
    Abstract [en]

    Tactile perception can be investigated through ex vivo friction measurements using a so-called ForceBoard™, providing objective assessments and savings in time and money, compared to a subjective human panel. In this work we aim to compare excised skin versus VitroSkin® as model substrates for tactile friction measurements. A further aim is to detect possible differences between traditional surfactant-based creams, and a particle-stabilized (Pickering) cream and investigate how the different substrates affect the results obtained. It was found that the difference in tactile friction between excised skin and VitroSkin® was small on untreated substrates. When topical creams were applied, the same trends were observed for both substrates, although the frictional variation over time relates to the difference in surface structure between the two substrates. The results also confirmed that there is a difference between starch-based Pickering formulations and surfactant-based creams after application, indicating that the latter is greasier than Pickering cream. It was also shown that the tactile friction of Pickering emulsions was consistently high even with high amounts of oil, indicating a non-greasy, and non-sticky formulation. The characteristics of starch-stabilized Pickering formulations make them promising candidates in the development of surfactant-free topical formulations with unique tactile properties.

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  • 12.
    Gidvall, Sanna
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Björklund, Sebastian
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Feiler, Adam
    Nanologica AB; KTH, Royal Institute of Technology.
    Dahlström, Bengt
    CTC Clinical Trial Consultants AB.
    Rönn, Robert
    Orexo AB.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Valetti, Sabrina
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    A novel versatile flow-donor chamber as biorelevant ex-vivo test assessing oral mucoadhesive formulations2021In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 166, article id 105983Article in journal (Refereed)
    Abstract [en]

    Oral transmucosal drug delivery is a non-invasive administration route for rapid therapeutic onset and greater bioavailability avoiding the first-pass metabolism. Mucoadhesive formulations are advantageous as they may retain the drug at the administration site. Proper equipment to assess mucoadhesive properties and corresponding drug absorption is fundamental for the development of novel drug delivery systems. Here we developed a new flow-through donor chamber for well-established diffusion cells, and we tested the effects on drug and formulation retention in situ of adding mucoadhesive polymers or mesoporous silica particles to a reference formulation. Mesoporous silica particles are of particular interest as they may be used to encapsulate and retain drug molecules. Compared to other ex-vivo methods described in literature for assessing mucoadhesive performance and transmucosal drug delivery, this new donor chamber provides several advantages: i) it reflects physiological conditions better as a realistic saliva flow can be provided over the administration site, ii) it is versatile since it can be mounted on any kind of vertical diffusion cell allowing simultaneous detection of drug retention at the administration site and drug permeation through the tissue, and iii) it enables optical quantification of formulations residence time aided by image processing. This new flow-through donor diffusion cell set-up proved sensitive to differentiate a reference formulation from one where 20 %(w/w) Carbomer was added (to further improve the mucoadhesive properties), with respect to both drug and formulation residence times. We also found that mesoporous silica particles, investigated as particles only and mixed together with the reference formulation, gave very similar drug and formulation retention to what we observed with the mucoadhesive Carbomer. However, after some time (>30 min) it became obvious that the tablet excipients in the reference formulation promote particle retention on the mucosa. This work provides a new simple and versatile biorelevant test for the evaluation of oral mucoadhesive formulations and paves the way for further studies on mesoporous silica particles as valuable excipients for enhancing oral mucoadhesion.

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  • 13.
    Valetti, Sabrina
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. Nanologica AB.
    Thomsen, Hanna
    University of Gothenburg.
    Wankar, Jitendra
    Istituto per la Sintesi Organica e la Fotoreattività, Italy.
    Falkman, Peter
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Manet, Ilse
    Istituto per la Sintesi Organica e la Fotoreattività, Italy.
    Feiler, Adam
    Nanologica AB; KTH.
    Ericson, Marica B
    University of Gothenburg.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Can mesoporous nanoparticles promote bioavailability of topical pharmaceutics?2021In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 602, article id 120609Article in journal (Refereed)
    Abstract [en]

    When applied to skin, particulate matter has been shown to accumulate in hair follicles. In addition to follicles, the skin topography also incorporates trench-like furrows where particles potentially can accumulate; however, the furrows have not been as thoroughly investigated in a drug delivery perspective. Depending on body site, the combined follicle orifices cover up to 10% of the skin surface, while furrows can easily cover 20%, reaching depths exceeding 25 µm. Hence, porous particles of appropriate size and porosity could serve as carriers for drugs to be released in the follicles prior to local or systemic absorption. In this paper, we combine multiphoton microscopy, scanning electron microscopy, and Franz cell diffusion technology to investigate ex-vivo skin accumulation of mesoporous silica particles (average size of 400-600 nm, 2, and 7 µm, respectively), and the potential of which as vehicles for topical drug delivery of the broad-spectrum antibiotic metronidazole. We detected smaller particles (400-600 nm) in furrows at depths of about 25 µm, also after rinsing, while larger particles (7 µm) where located more superficially on the skin. This implies that appropriately sized porous particles may serve as valuable excipients in optimizing bioavailability of topical formulations. This work highlights the potential of skin furrows for topical drug delivery.

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  • 14.
    Lind, Tania K.
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Nilsson, Emelie J.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Wyler, Benjamin
    LONZA AG, Switzerland.
    Scherer, Dieter
    LONZA AG, Switzerland.
    Skansberger, Tatyana
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Morin, Maxim
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Kocherbitov, Vitaly
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Effects of ethylene oxide chain length on crystallization of polysorbate 80 and its related compounds2021In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 592, p. 468-484, article id S0021-9797(21)00078-3Article in journal (Refereed)
    Abstract [en]

    As a result of the synthesis protocol polyoxyethylene sorbitan monooleate (polysorbate 80, PS80) is a highly complex mixture of compounds. PS80 was therefore separated into its main constituents, e.g. polyoxyethylene isosorbide esters and polyoxyethylene esters, as well as mono- di- and polyesters using preparative high-performance liquid chromatography. In this comprehensive study the individual components and their ethoxylation level were verified by matrix assisted laser desorption/ionization time-of-flight and their thermotropic behavior was analyzed using differential scanning calorimetry and X-ray diffraction. A distinct correlation was found between the average length of the ethylene oxide (EO) chains in the headgroup and the individual compounds' ability to crystallize. Importantly, a critical number of EO units required for crystallization of the headgroup was determined (6 EO units per chain or 24 per molecule). The investigation also revealed that the hydrocarbon tails only crystallize for polyoxyethylene sorbitan esters if saturated. PS80 is synthesized by reacting with approximately 20 mol of EO per mole of sorbitol, however, the number of EO units in the sorbitan ester in commercial PS80 products is higher than the expected 20 (5 EO units per chain). The complex behavior of all tested compounds revealed that if the amount of several of the linear by-products is reduced, the number of EO units in the chains will stay below the critical number and the product will not be able to crystallize by the EO chains.

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  • 15.
    Jankovskaja, Skaidre
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Rezeli, Melinda
    Clinical Protein Science and Imaging, Department of Biomedical Engineering, Lund University, Lund, Sweden.
    Marko-Varga, György
    Clinical Protein Science and Imaging, Department of Biomedical Engineering, Lund University, Lund, Sweden.
    Ruzgas, Tautgirdas
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Björklund, Sebastian
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Non-invasive skin sampling of tryptophan/kynurenine ratio in vitro towards a skin cancer biomarker2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 678Article in journal (Refereed)
    Abstract [en]

    The tryptophan to kynurenine ratio (Trp/Kyn) has been proposed as a cancer biomarker. Non-invasive topical sampling of Trp/Kyn can therefore serve as a promising concept for skin cancer diagnostics. By performing in vitro pig skin permeability studies, we conclude that non-invasive topical sampling of Trp and Kyn is feasible. We explore the influence of different experimental conditions, which are relevant for the clinical in vivo setting, such as pH variations, sampling time, and microbial degradation of Trp and Kyn. The permeabilities of Trp and Kyn are overall similar. However, the permeated Trp/Kyn ratio is generally higher than unity due to endogenous Trp, which should be taken into account to obtain a non-biased Trp/Kyn ratio accurately reflecting systemic concentrations. Additionally, prolonged sampling time is associated with bacterial Trp and Kyn degradation and should be considered in a clinical setting. Finally, the experimental results are supported by the four permeation pathways model, predicting that the hydrophilic Trp and Kyn molecules mainly permeate through lipid defects (i.e., the porous pathway). However, the hydrophobic indole ring of Trp is suggested to result in a small but noticeable relative increase of Trp diffusion via pathways across the SC lipid lamellae, while the shunt pathway is proposed to slightly favor permeation of Kyn relative to Trp.

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  • 16.
    Mojumdar, Enamul Haque
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Madsen, Lone Bruhn
    Timeline Bioresearch AB.
    Hansson, Henri
    Galenica AB.
    Taavoniku, Ida
    Timeline Bioresearch AB.
    Kristensen, Klaus
    Timeline Bioresearch AB.
    Persson, Christina
    Lund University.
    Morén, Anna Karin
    Galenica AB.
    Mokso, Rajmund
    Lund University.
    Schmidtchen, Artur
    Lund University; University of Copenhagen, Denmark.
    Ruzgas, Tautgirdas
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Probing Skin Barrier Recovery on Molecular Level Following Acute Wounds: An In Vivo/Ex Vivo Study on Pigs.2021In: Biomedicines, E-ISSN 2227-9059, Vol. 9, no 4, article id 360Article in journal (Refereed)
    Abstract [en]

    Proper skin barrier function is paramount for our survival, and, suffering injury, there is an acute need to restore the lost barrier and prevent development of a chronic wound. We hypothesize that rapid wound closure is more important than immediate perfection of the barrier, whereas specific treatment may facilitate perfection. The aim of the current project was therefore to evaluate the quality of restored tissue down to the molecular level. We used Göttingen minipigs with a multi-technique approach correlating wound healing progression in vivo over three weeks, monitored by classical methods (e.g., histology, trans-epidermal water loss (TEWL), pH) and subsequent physicochemical characterization of barrier recovery (i.e., small and wide-angle X-ray diffraction (SWAXD), polarization transfer solid-state NMR (PTssNMR), dynamic vapor sorption (DVS), Fourier transform infrared (FTIR)), providing a unique insight into molecular aspects of healing. We conclude that although acute wounds sealed within two weeks as expected, molecular investigation of stratum corneum (SC) revealed a poorly developed keratin organization and deviations in lipid lamellae formation. A higher lipid fluidity was also observed in regenerated tissue. This may have been due to incomplete lipid conversion during barrier recovery as glycosphingolipids, normally not present in SC, were indicated by infrared FTIR spectroscopy. Evidently, a molecular approach to skin barrier recovery could be a valuable tool in future development of products targeting wound healing.

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  • 17.
    Proksch, Ehrhardt
    et al.
    Department of Dermatology, University of Kiel, Kiel, Germany.
    Berardesca, Enzo
    San Gallicano Dermatological Institute, Rome, Italy.
    Misery, Laurent
    Department of Dermatology, University Hospital of Brest, Brest, France; Laboratory of Neurosciences, University of Western Brittany, Brest, France.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Bouwstra, Joke
    Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden, The Netherlands.
    Dry skin management: practical approach in light of latest research on skin structure and function.2020In: Journal of dermatological treatment (Print), ISSN 0954-6634, E-ISSN 1471-1753, Vol. 31, no 7, p. 716-722Article in journal (Refereed)
    Abstract [en]

    Dry skin is a common condition that is attributed to a lack of water in the stratum corneum. With the availability of new technologies, light has been shed on the pathophysiology of dry skin at the molecular level. With the aim to discuss implications of this latest research for the optimal formulation of emollients designed to treat dry skin, five specialists met in November 2017. Research on three topics thereby provided particularly detailed new insights on how to manage dry skin: research on the lipid composition and organization of the stratum corneum, research on natural moisturizing factors, and research on the peripheral nervous system. There was consensus that latest research expands the rationale to include physiological lipids in an emollient used for dry skin, as they were found to be essential for an adequate composition and organization in the stratum corneum but are reduced in dry skin. Latest findings also confirmed the incorporation of carefully selected humectants into a topical emollient for dry skin, given the reduced activity of enzymes involved in the synthesis of moisturizing factors when skin is dry. Overall, the group of specialists concluded that the previous concept of the five components for an ideal emollient for dry skin is well in accordance with latest research.

  • 18.
    Mukherjee, Biswajit
    et al.
    Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Ho, Paul Chi-Lui
    Department of Pharmacy, National University of Singapore, Singapore.
    Karunaratne, Veranja
    Department of Chemistry, University of Peradeniya, Peradeniya, Sri Lanka.
    Editorial: Advances in Drug Formulation2020In: Frontiers in Pharmacology, E-ISSN 1663-9812, Vol. 11, article id 608771Article in journal (Other academic)
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  • 19.
    Gustafsson, Anna
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Prgomet, Zdenka
    Malmö University, Faculty of Odontology (OD).
    Jankovskaja, Skaidre
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Ruzgas, Tautgirdas
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Ohlsson, Lars
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Gjörloff Wingren, Anette
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Effect of IFN-γ on the kynurenine/tryptophan ratio in monolayer-cultured keratinocytes and a 3D reconstructed human epidermis model2020In: Journal of dermatological science (Amsterdam), ISSN 0923-1811, E-ISSN 1873-569X, Vol. 99, no 3, p. 177-184, article id S0923-1811(20)30234-6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Interferon-gamma (IFN-γ) represents a potent inducer for keratinocyte inflammatory and immune activation in vitro. Since tryptophan (trp) conversion to kynurenine (kyn) is involved in inflammation, the topical kyn/trp ratio may serve as a biomarker of skin inflammation. However, the trp metabolism in keratinocytes exposed to IFN-γ is not yet fully understood.

    OBJECTIVE: The aim of this study was to establish a human epidermis model in order to quantify cytokine and kyn/trp secretion from IFN-γ stimulated cells and tissues. Moreover, to compare the cell response of 2D-cultured keratinocytes and the 3D epidermis model.

    METHODS: Polycarbonate filters were used on which primary keratinocytes could attach and stratify in order to form the typical layers of reconstructed human epidermis (RHE). After IFN-γ treatment, secretion of kyn/trp was measured by high performance liquid chromatography. Gene and protein expression of indoleamine 2,3-dioxygenase 1 (IDO) was analyzed with real-time PCR and immunohistochemistry. The secretion of cytokines was quantified with ELISA.

    RESULTS: Trp catabolism to kyn was significantly increased (P < 0.01) in the 2D culture in response to IFN-γ treatment. Before kyn secretion, IDO was strongly upregulated (P < 0.001). IFN-γ treatment also increased the secretion of IL-6 and IL-8 from the keratinocytes. In the RHE, IDO was upregulated by IFN-γ, and kyn secretion could be detected. Interestingly, IDO expression was only present in the basal cells of the RHE.

    CONCLUSION: Our results suggest that IFN-γ acts as an inducer of trp degradation preferentially in undifferentiated keratinocytes, indicated by the IDO expression in the basal layer of the RHE.

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  • 20.
    Falk, Yana Znamenskaya
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Runnsjö, Anna
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Pettigrew, Anthony
    Anthony Pettigrew Associates Ltd, Liverpool, UK.
    Scherer, Dieter
    ApisPharma AG, CH-4242 Laufen, Switzerland.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Kocherbitov, Vitaly
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Interactions of Perfluorohexyloctane With Polyethylene and Polypropylene Pharmaceutical Packaging Materials.2020In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 109, no 7, p. 2180-2188, article id S0022-3549(20)30185-4Article in journal (Refereed)
    Abstract [en]

    Semifluorinated alkanes (SFAs) are aprotic solvents, which may be used as drug solvents for topical ocular applications, for instance, in dry eye syndrome. Their physical properties suggest that they might be prone to interaction with plastic materials, such as, polyethylene (PE) and polypropylene (PP), which are commonly used as packaging materials for pharmaceutical products. In this study, we investigate interactions of PE and PP with a liquid SFA perfluorohexyloctane (PFHO) using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and cross-polarized light microscopy. Binary phase diagrams of PFHO-PE and PFHO-PP systems demonstrating interactions of PFHO with the polymeric materials were constructed based on DSC data. According to this data, PFHO tends to lower the melting temperatures of PE and PP. The equilibrium values of solubilities of the polymers in PFHO and PFHO in the polymers were obtained by extrapolation of melting enthalpy data. Absorption of PFHO by PE and PP materials at ambient conditions after four weeks of equilibration was also studied by TGA. From the presented results, it may be concluded that thorough studies of interactions of PE or PP with SFAs are required when these materials are used as packaging components in SFA-based formulations.

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  • 21.
    Nilsson, Emelie J.
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Lind, Tania Kjellerup
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Scherer, Dieter
    LONZA AG, Basel, CH-4002, Switzerland.
    Skansberger, Tatyana
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Mortensen, Kell
    Niels Bohr Institute, University of Copenhagen, Copenhagen, DK-2100, Denmark.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Kocherbitov, Vitaly
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Mechanisms of crystallisation in polysorbates and sorbitan esters2020In: CrystEngComm, ISSN 1466-8033, E-ISSN 1466-8033, Vol. 22, no 22, p. 3840-3853Article in journal (Refereed)
    Abstract [en]

    Polysorbates (PS), commonly known as Tween (TM), are some of the most extensively used excipients and protein stabilisers in biopharmaceutical products worldwide. It is stipulated in the pharmacopoeia specifications that these ethoxylated surfactants are complex mixtures comprised of a wealth of molecular species. While little is known about the propensity of PSs to crystallise, they are used in applications ranging from food products, cosmetics, different types of drug dosage forms like creams and oral products to parenteral applications. However, in recent years a range of issues and safety concerns have appeared when using them for stabilising biopharmaceutical products including precipitation, particle formation, and adverse biological effects. Therefore, the aim of this study was to thoroughly characterise the thermotropic behaviour and mechanism of crystallisation of polysorbates with different hydrocarbon tails and their non-ethoxylated sorbitan ester equivalents for comparison. A systematic and comprehensive product characterisation was carried out, taking advantage of a combination of complementary techniques such as differential scanning calorimetry, matrix assisted laser desorption ionisation time-of-flight and small- and wide-angle X-ray diffraction. We show that polysorbate 80, having an unsaturated hydrocarbon tail, crystallises by the ethylene oxide chains in the headgroup. Polysorbate 20, 40, and 60, containing saturated hydrocarbon esters tails, crystallise not only by the ethylene oxide chains but also by their hydrocarbon tails. An analogous behaviour was observed for the PS non-ethoxylated equivalents, the sorbitan esters. Sorbitan esters with saturated hydrocarbon tails displayed a crystallisation of the tail upon cooling, whereas the sorbitan ester with unsaturated hydrocarbon tail displayed no crystallisation.

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  • 22.
    Morin, Maxim
    et al.
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Ruzgas, Tautgirdas
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Svedenhag, Per
    SciBase AB, Sundbyberg, Sweden.
    Anderson, Christopher D
    Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
    Ollmar, Stig
    Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Björklund, Sebastian
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Skin hydration dynamics investigated by electrical impedance techniques in vivo and in vitro.2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 17218Article in journal (Refereed)
    Abstract [en]

    Skin is easily accessible for transdermal drug delivery and also attractive for biomarker sampling. These applications are strongly influenced by hydration where elevated hydration generally leads to increased skin permeability. Thus, favorable transdermal delivery and extraction conditions can be easily obtained by exploiting elevated skin hydration. Here, we provide a detailed in vivo and in vitro investigation of the skin hydration dynamics using three techniques based on electrical impedance spectroscopy. Good correlation between in vivo and in vitro results is demonstrated, which implies that simple but realistic in vitro models can be used for further studies related to skin hydration (e.g., cosmetic testing). Importantly, the results show that hydration proceeds in two stages. Firstly, hydration between 5 and 10 min results in a drastic skin impedance change, which is interpreted as filling of superficial voids in skin with conducting electrolyte solution. Secondly, a subtle impedance change is observed over time, which is interpreted as leveling of the water gradient across skin leading to structural relaxation/changes of the macromolecular skin barrier components. With respect to transdermal drug delivery and extraction of biomarkers; 1 h of hydration is suggested to result in beneficial and stable conditions in terms of high skin permeability and extraction efficiency.

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  • 23.
    Jankovskaja, Skaidre
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Labrousse, Anais
    Department of Biological Engineering, Clermont Auvergne University, 63100, Aubiere, France.
    Prevaud, Lea
    Faculty of Sciences, University of Montpellier, 34085, Montpellier, France.
    Holmqvist, Bo
    ImaGene-iT, Medicon Village, 223 81, Lund, Sweden.
    Brinte, Anders
    ImaGene-iT, Medicon Village, 223 81, Lund, Sweden.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Rezeli, Melinda
    Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, BMC D13, 221 84, Lund, Sweden.
    Marko-Varga, Gyorgy
    Clinical Protein Science & Imaging, Biomedical Centre, Department of Biomedical Engineering, Lund University, BMC D13, 221 84, Lund, Sweden.
    Ruzgas, Tautgirdas
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Visualisation of H2O2 penetration through skin indicates importance to develop pathway-specific epidermal sensing2020In: Microchimica Acta, ISSN 0026-3672, E-ISSN 1436-5073, Vol. 187, no 12, article id 656Article in journal (Refereed)
    Abstract [en]

    Elevated amounts of reactive oxygen species (ROS) including hydrogen peroxide (H2O2) are observed in the epidermis in different skin disorders. Thus, epidermal sensing of H2O2 should be useful to monitor the progression of skin pathologies. We have evaluated epidermal sensing of H2O2 in vitro, by visualising H2O2 permeation through the skin. Skin membranes were mounted in Franz cells, and a suspension of Prussian white microparticles was deposited on the stratum corneum face of the skin. Upon H2O2 permeation, Prussian white was oxidised to Prussian blue, resulting in a pattern of blue dots. Comparison of skin surface images with the dot patterns revealed that about 74% of the blue dots were associated with hair shafts. The degree of the Prussian white to Prussian blue conversion strongly correlated with the reciprocal resistance of the skin membranes. Together, the results demonstrate that hair follicles are the major pathways of H2O2 transdermal penetration. The study recommends that the development of H2O2 monitoring on skin should aim for pathway-specific epidermal sensing, allowing micrometre resolution to detect and quantify this ROS biomarker at hair follicles. Graphical abstract

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  • 24.
    Ali, Abdullah
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Wahlgren, Marie
    Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden.
    Rembratt-Svensson, Birgitta
    Bioglan AB, Malmö, Sweden.
    Daftani, Ameena
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Falkman, Peter
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Wollmer, Per
    Department of Translational Medicine, Faculty of Medicine, Lund University, Malmö, Sweden.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Dehydration affects drug transport over nasal mucosa2019In: Drug Delivery, ISSN 1071-7544, E-ISSN 1521-0464, Vol. 26, no 1, p. 831-840Article in journal (Refereed)
    Abstract [en]

    Formulations for nasal drug delivery often rely on water sorption to adhere to the mucosa, which also causes a higher water gradient over the tissue and subsequent dehydration. The primary aim of this study was therefore to evaluate mucosal response to dehydration and resolve the hypothesis that mucoadhesion achieved through water sorption could also be a constraint for drug absorption via the nasal route. The effect of altering water activity of the vehicle on Xylometazoline HCl and Cr-EDTA uptake was studied separately using flow through diffusion cells and excised porcine mucosa. We have shown that a modest increase in the water gradient over mucosa induces a substantial decrease in drug uptake for both Xylometazoline HCl and Cr-EDTA. A similar result was obtained when comparing two different vehicles on the market; Nasoferm (Nordic Drugs, Sweden) and BLOX4 (Bioglan, Sweden). Mucoadhesion based on water sorption can slow down drug uptake in the nasal cavity. However, a clinical study is required to determine whether prolonged duration of the vehicle or preventing dehydration of the mucosa is the most important factor for improving bioavailability.

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  • 25.
    Hernández, Aura Rocio
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. Department of Pharmacy, Universidad Nacional de Colombia, Bogota 1101, Colombia.
    Boutonnet, Marine
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Svensson, Birgitta
    Bioglan AB, SE-202 13 Malmö, Sweden.
    Butler, Eile
    Biogaia AB, SE-223 62 Lund, Sweden.
    Lood, Rolf
    Department of Clinical Science, Lund University, SE-221 84 Lund, Sweden.
    Blom, Kristina
    Medibiome AB, SE-435 43 Pixbo, Sweden.
    Vallejo, Bibiana
    Department of Pharmacy, Universidad Nacional de Colombia, Bogota 1101, Colombia.
    Anderson, Chris
    Department of Clinical and Experimental Medicine, Linköping University, SE-581 83 Linköping, Sweden.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Ruzgas, Tautgirdas
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Björklund, Sebastian
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    New concepts for transdermal delivery of oxygen based on catalase biochemical reactions studied by oxygen electrode amperometry2019In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 306, p. 121-129Article in journal (Refereed)
    Abstract [en]

    The development of formulation concepts for improved skin tissue oxygenation, including methods for measuring oxygen (O) transport across biological barriers, are important research topics with respect to all processes that are affected by the O concentration, such as radiation therapy in oncology treatments, wound healing, and the general health status of skin. In this work we approach this topic by a novel strategy based on the antioxidative enzyme catalase, which is naturally present in the skin organ where it enables conversion of the reactive oxygen species hydrogen peroxide (HO) into O. We introduce various applications of the skin covered oxygen electrode (SCOE) as an in-vitro tool for studies of catalase activity and function. The SCOE is constructed by placing an excised skin membrane directly on an O electrode and the methodology is based on measurements of the electrical current generated by reduction of O as a function of time (i.e. chronoamperometry). The results confirm that a high amount of native catalase is present in the skin organ, even in the outermost stratum corneum (SC) barrier, and we conclude that excised pig skin (irrespective of freeze-thaw treatment) represents a valid model for ex vivo human skin for studying catalase function by the SCOE setup. The activity of native catalase in skin is sufficient to generate considerable amounts of O by conversion from HO and proof-of-concept is presented for catalase-based transdermal O delivery from topical formulations containing HO. In addition, we show that this concept can be further improved by topical application of external catalase on the skin surface, which enables transdermal O delivery from 50 times lower concentrations of HO. These important results are promising for development of novel topical or transdermal formulations containing low and safe concentrations of HO for skin tissue oxygenation. Further, our results indicate that the O production by catalase, derived from topically applied S. epidermidis (a simple model for skin microbiota) is relatively low as compared to the O produced by the catalase naturally present in skin. Still, the catalase activity derived from S. epidermidis is measurable. Taken together, this work illustrates the benefits and versatility of the SCOE as an in vitro skin research tool and introduces new and promising strategies for transdermal oxygen delivery, with simultaneous detoxification of HO, based on native or topically applied catalase.

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  • 26.
    Eskandari, Mahboubeh
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Center of Excellence in Electrochemistry, School of Chemistry, University of Tehran, Tehran, Iran; Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
    Rembiesa, Jadwiga
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. In vitro Plant-tech AB, 216 18, Limhamn, Sweden.
    Startaite, Lauryna
    In vitro Plant-tech AB, 216 18, Limhamn, Sweden.
    Holefors, Anna
    In vitro Plant-tech AB, 216 18, Limhamn, Sweden.
    Valanciute, Audrone
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Faridbod, Farnoush
    Center of Excellence in Electrochemistry, School of Chemistry, University of Tehran, Tehran, Iran.
    Ganjali, Mohammad Reza
    Center of Excellence in Electrochemistry, School of Chemistry, University of Tehran, Tehran, Iran; Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Ruzgas, Tautgirdas
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Polyphenol-hydrogen peroxide reactions in skin: In vitro model relevant to study ROS reactions at inflammation2019In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 1075, p. 91-97Article in journal (Refereed)
    Abstract [en]

    Antioxidants are important to protect and maintain biological barriers, such as the skin. Antioxidant effects are often assessed using clinical trials, however these tests are costly and time consuming. In this work we introduce a skin membrane-covered oxygen electrode (SCOE) as an in vitro tool for monitoring H2O2 and antioxidant reactions in skin. The SCOE gives amperometric response to H2O2 concentrations down to 0.05 mM. More importantly, the electrode allows measurements of polyphenol penetration and reaction with H2O2 in skin. Measurements with SCOE show that lipophilic polyphenols such as quercetin, piceatannol, resveratrol, and plant extract from Plantago major impose their antioxidant effect in skin within 2-20 min. Rutin is however too hydrophilic to penetrate into stratum corneum and therefore cannot deliver its antioxidant effect during similar time interval. The measurements are interpreted considering polyphenol partition-penetration through stratum corneum and the reaction with the H2O2-catalase system in the skin. The contribution of other enzymes will be addressed in the future. (C) 2019 Elsevier B.V. All rights reserved.

  • 27.
    Falk, Yana Znamenskaya
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Pedersen, Jan Skov
    Department of Chemistry and Interdisciplinary Nanosciene Center (iNANO) , Aarhus University , 8000 Aarhus C, Denmark.
    Arnebrant, Thomas
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Kocherbitov, Vitaly
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Effects of Hydration on Structure and Phase Behavior of Pig Gastric Mucin Elucidated by SAXS2018In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 122, no 30, p. 7539-7546Article in journal (Refereed)
    Abstract [en]

    In this work small-angle X-ray scattering (SAXS) was used to study hydration and temperature-induced changes of pig gastric mucin (PGM) within the entire concentration range. The scattering is interpreted as originating from PGM fiber-like structures that adopt rod-like bottle-brush conformation in dilute solutions. On the basis of the knowledge about molecular structure of mucins and SAXS data for dilute solutions, we propose a theoretical model for predicting mucin conformation in solution and calculate the corresponding scattering profile. This bottle-brush model comprises a protein backbone with carbohydrate side chains and corresponding structural parameters, such as grafting distance and lengths of the backbone and side chains. It describes the experimental PGM data from dilute solutions in the full q range very well. It furthermore suggests that the carbohydrate side chains are grafted with a regular separation of around 5 nm and a length of 14 nm. The cross-section size with a radius of about 1 nm is also in accordance with the size of the carbohydrate units. Structuring of PGM solutions at higher concentrations was investigated by analyzing semidilute and concentrated PGM samples. Starting at about 20 wt %, Bragg peaks become clearly visible indicating a more ordered mucin system. In very dehydrated and fully dry mucin samples these peaks are not present indicating lack of long-range order. The SAXS data show that the structural change occurring at about 80 wt % mucin and 25 degrees C corresponds to a glass transition in agreement with our previous calorimetric results. Temperature also has an effect on the phase behavior of mucin. At intermediate levels of hydration, a phase transition is observed at about 60-70 degrees C. The main Bragg peak appears to split in two, indicating formation of a different structure at elevated temperatures. These findings are used to improve the PGM water phase diagram.

  • 28.
    Ullah, Sana
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Hamade, Fadi
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. Sterisol AB, 592 23 Vadstena, Sweden.
    Bubniene, Urte
    Department of Physical Chemistry and Geoscience, Vilnius University, LT-03225 Vilnius, Lithuania.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Ramanavicius, Arunas
    Department of Physical Chemistry and Geoscience, Vilnius University, LT-03225 Vilnius, Lithuania.
    Ramanaviciene, Almira
    NanoTechnas - Center of Nanotechnology and Materials Science, Faculty of Chemistry and Geosciences, Vilnius University, LT-03225 Vilnius, Lithuania.
    Ruzgas, Tautgirdas
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    In-vitro model for assessing glucose diffusion through skin2018In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 110, p. 175-179Article in journal (Refereed)
    Abstract [en]

    Pig ear skin membrane-covered glucose biosensor based on oxygen electrode has been assessed as a tool to evaluate glucose penetration through skin in-vitro. For this, glucose oxidase (GOx) was immobilised on oxygen electrode and covered with the skin membrane. Exposing this electrode to the solution of glucose resulted in glucose penetration though skin membrane, its oxidation catalysed by GOx, consumption of O-2 and decrease of the current of the oxygen electrode. By processing the biosensor responses to glucose, we found that glucose penetration through 250 pm thick skin membrane is slow; 90% of steady-state current response was reached in 32(+/- 22) min. Apparent diffusion coefficient for glucose in skin was found to be equal to 0.15( +/- 07)* 10(-6) cm(2) s(-1). This value is 45 times lower than glucose diffusion coefficient in water. Tape-stripping of stratum corneum (SC) allows considerably faster glucose penetration. The electrodes covered with tape-stripped skin reached 90% of steady-state current response in 5.0(+/- 2.7) min. The theoretical estimate of glucose flux through SC was considered exploiting four-pathway theory of transdermal penetration. Theoretical flux values were more that three orders lower than measured experimentally. This high discrepancy might indicate that glucose penetration through healthy human skin could be even slower, allowing much lower flux, than it was found in our study for skin membranes from pig ears.

  • 29.
    Rembiesa, Jadwiga
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces. In vitro Plant-tech AB.
    Ruzgas, Tautgirdas
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Holefors, Anna
    In vitro Plant-tech AB.
    The impact of pollution on skin and proper efficacy testing for anti-pollution claims2018In: Cosmetics, ISSN 2079-9284, Vol. 5, no 1, article id 4Article in journal (Refereed)
    Abstract [en]

    Exposure to pollution can cause oxidative stress, premature ageing, inflammation, and diseases. Since most of us are exposed to pollution, protection is important. This can be achieved through skin protection or through protection with respect to food and food supplements. There is a wide range of products on the market with anti-pollution claims. However, it is important that these claims are thoroughly validated by proper efficacy testing. When skin cells are exposed to pollution factors, changes in a number of skin properties can be observed, such as lipid composition, lipid and protein oxidation, pH, sebum secretion rate, oxidative stress, inflammation markers, and collagen and elastin levels. These can be measured and used as markers to verify anti-pollution claims. In the present review, we summarize some of the most important in vitro and in vivo tests that are used to determine if an ingredient or formulation has anti-pollution efficacy. © 2018 by the authors.

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  • 30.
    Ali, Abdullah
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Wahlgren, Marie
    Food Technology, Engineering and Nutrition, Lund University, P.O. Box 124, SE-221 00, Lund, Sweden.
    Pedersen, Lina
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Engblom, Johan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Will a water gradient in oral mucosa affect transbuccal drug absorption?2018In: Journal of Drug Delivery Science and Technology, ISSN 1773-2247, Vol. 48, p. 338-345Article in journal (Refereed)
    Abstract [en]

    Formulations for buccal drug delivery often comprise polymers to facilitate mucoadhesion based on water sorption. The main objective of the current study was therefore to evaluate the effect of dehydration on drug uptake through oral mucosa. We have used diffusion cells with excised porcine mucosa to study uptake of three alternative drugs (i.e., Metronidazole, Benzydamine and Xylometazoline) together with polyethylene glycol (PEG) as the model polymer for adjusting water activity in the test solutions. Taking drug activity into account, we can conclude that addition of PEG results in a drug flux through mucosa that is about two times lower for Metronidazole and more than 40 times lower for Xylometazoline compared to that from a pure PBS-solution. However, for Benzydamine the uptake through mucosa was more or less the same, which could possibly be due to the high PEG-concentration (65 wt%) affecting the dissociation constant and thus the permeability. These results indicate that an increased water gradient may have the same limiting effect on permeability through oral mucosa as previously seen for skin. Thus, water gradient effects should be a factor to consider when developing buccal adhesive formulations.

  • 31.
    Nocchi, Sarah
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Björklund, Sebastian
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Svensson, Birgitta
    Bioglan AB, SE-202 13 Malmö, Sweden.
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Ruzgas, Tautgirdas
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Electrochemical monitoring of native catalase activity in skin using skin covered oxygen electrode2017In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 93, p. 9-13Article in journal (Refereed)
    Abstract [en]

    A skin covered oxygen electrode, SCOE, was constructed with the aim to study the enzyme catalase, which is part of the biological antioxidative system present in skin. The electrode was exposed to different concentrations of H2O2 and the amperometric current response was recorded. The observed current is due to H2O2 penetration through the outermost skin barrier (referred to as the stratum corneum, SC) and subsequent catalytic generation of O2 by catalase present in the underlying viable epidermis and dermis. By tape-stripping the outermost skin layers we demonstrate that SC is a considerable diffusion barrier for H2O2 penetration. Our experiments also indicate that skin contains a substantial amount of catalase, which is sufficient to detoxify H2O2 that reaches the viable epidermis after exposure of skin to high concentrations of peroxide (0.5–1 mM H2O2). Further, we demonstrate that the catalase activity is reduced at acidic pH, as compared with the activity at pH 7.4. Finally, experiments with often used penetration enhancer thymol shows that this compound interferes with the catalase reaction. Health aspect of this is briefly discussed. Summarizing, the results of this work show that the SCOE can be utilized to study a broad spectrum of issues involving the function of skin catalase in particular, and the native biological antioxidative system in skin in general.

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  • 32.
    Runnsjo, Anna
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Kocherbitov, Vitaly
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Graf, Gesche
    Novaliq GmbH, Im Neuenheimer Feld 515, Heidelberg, Germany.
    Pettigrew, Anthony
    Novaliq GmbH, Im Neuenheimer Feld 515, Heidelberg, Germany.
    Scherer, Dieter
    Novaliq GmbH, Im Neuenheimer Feld 515, Heidelberg, Germany.
    Mortensen, Kell
    Niels Bohr Institute, University of Copenhagen, Universitetsparken 5, København Ø, 2100, Denmark.
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Semifluorinated alkanes and alkanes: a phase study of the perfluorohexyloctane - tetradecane system2017In: Journal of Chemical Thermodynamics, ISSN 0021-9614, E-ISSN 1096-3626, Vol. 105, p. 352-361Article in journal (Refereed)
    Abstract [en]

    The binary system perfluorohexyloctane (F6H8)–tetradecane (C14) was investigated in order to increase understanding of interactions of semifluorinated alkanes (SFAs) with hydrophobic molecules. The thermal phase behavior for F6H8 and C14 and their mixtures was determined using DSC. The activity coefficients for both components in the mixtures were calculated and Gibbs energy of mixing was determined. Furthermore, enthalpies of mixing were determined with ITC and structural investigations of the solid and the liquid phases were performed with SAXS and SWAXD. It was found that F6H8 displays one solid-solid transition at −42.3 °C (ΔH = 1.1 kJ/mol) and one solid-liquid transition at −5.9 °C (ΔH = 16.6 kJ/mol). Due to the low enthalpy of the solid-liquid transition it is likely that F6H8 is not fully crystallized in the solid phase but partly amorphous. The F6H8–C14 system displays a eutectic phase behavior and the liquid mixtures display a positive deviation from ideal mixing. C14 crystalizes in a triclinic unit cell as shown before, whereas crystallization of F6H8 in a lamellar rippled phase is shown for the first time. This ripple phase comprises a bilayer of tilted alternating heavily interdigitated F6H8 molecules in an oblique subunit cell.

  • 33.
    Pham, Quoc Dat
    et al.
    Division of Physical Chemistry, Chemistry Department, Lund University, P.O. Box 124, Lund, SE-221 00, Sweden.
    Björklund, Sebastian
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Topgaard, Daniel
    Division of Physical Chemistry, Chemistry Department, Lund University, P.O. Box 124, Lund, SE-221 00, Sweden.
    Sparr, Emma
    Division of Physical Chemistry, Chemistry Department, Lund University, P.O. Box 124, Lund, SE-221 00, Sweden.
    Chemical penetration enhancers in stratum corneum: Relation between molecular effects and barrier function2016In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 232, p. 175-187Article in journal (Refereed)
    Abstract [en]

    Skin is attractive for drug therapy because it offers an easily accessible route without first-pass metabolism. Transdermal drug delivery is also associated with high patient compliance and through the site of application, the drug delivery can be locally directed. However, to succeed with transdermal drug delivery it is often required to overcome the low permeability of the upper layer of the skin, the stratum corneum (SC). One common strategy is to employ so-called penetration enhancers that supposedly act to increase the drug passage across SC. Still, there is a lack of understanding of the molecular effects of so-called penetration enhancers on the skin barrier membrane, the SC. In this study, we provide a molecular characterization of how different classes of compounds, suggested as penetration enhancers, influence lipid and protein components in SC. The compounds investigated include monoterpenes, fatty acids, osmolytes, surfactant, and Azone. We employ natural abundance C-13 polarization transfer solid-state nuclear magnetic resonance (NMR) on intact porcine SC. With this method it is possible to detect small changes in the mobility of the minor fluid lipid and protein SC components, and simultaneously obtain information on the major fraction of solid SC components. The balance between fluid and solid components in the SC is essential to determine macroscopic material properties of the SC, including barrier and mechanical properties. We study SC at different hydration levels corresponding to SC in ambient air and under occlusion. The NMR studies are complemented with diffusion cell experiments that provide quantitative data on skin permeability when treated with different compounds. By correlating the effects on SC molecular components and SC barrier function, we aim at deepened understanding of diffusional transport in SC, and how this can be controlled, which can be utilized for optimal design of transdermal drug delivery formulations. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license.

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  • 34.
    Runnsjö, Anna
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Dabkowska, Aleksandra P
    Division of Physical Chemistry, Lund University, Lund, Sweden.
    Sparr, Emma
    Division of Physical Chemistry, Lund University, Lund, Sweden.
    Kocherbitov, Vitaly
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Arnebrant, Thomas
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Diffusion through Pig Gastric Mucin: Effect of Relative Humidity2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 6, article id e0157596Article in journal (Refereed)
    Abstract [en]

    Mucus covers the epithelium found in all intestinal tracts, where it serves as an important protecting barrier, and pharmaceutical drugs administrated by the oral, rectal, vaginal, ocular, or nasal route need to penetrate the mucus in order to reach their targets. Furthermore, the diffusion in mucus as well as the viscosity of mucus in the eyes, nose and throat can change depending on the relative humidity of the surrounding air. In this study we have investigated how diffusion through gels of mucin, the main protein in mucus, is affected by changes in ambient relative humidity (i.e. water activity). Already a small decrease in water activity was found to give rise to a significant decrease in penetration rate through the mucin gel of the antibacterial drug metronidazole. We also show that a decrease in water activity leads to decreased diffusion rate in the mucin gel for the fluorophore fluorescein. This study shows that it is possible to alter transport rates of molecules through mucus by changing the water activity in the gel. It furthermore illustrates the importance of considering effects of the water activity in the mucosa during development of potential pharmaceuticals.

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  • 35.
    Björklund, Sebastian
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Quoc Dat, Pham
    Physical Chemistry, The Center for Chemistry and Chemical Engineering, Lund University, Box 124, SE-221 00 Lund, Sweden.
    Bastholm Jensen, Louise
    LEO Pharma A/S, Industriparken 55, DK-2750 Ballerup, Denmark.
    Østergaard Knudsen, Nina
    LEO Pharma A/S, Industriparken 55, DK-2750 Ballerup, Denmark.
    Dencker Nielsen, Lars
    LEO Pharma A/S, Industriparken 55, DK-2750 Ballerup, Denmark.
    Ekelund, Katarina
    LEO Pharma A/S, Industriparken 55, DK-2750 Ballerup, Denmark.
    Ruzgas, Tautgirdas
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Sparr, Emma
    Physical Chemistry, The Center for Chemistry and Chemical Engineering, Lund University, Box 124, SE-221 00 Lund, Sweden.
    The effects of polar excipients transcutol and dexpanthenol on molecular mobility, permeability, and electrical impedance of the skin barrier2016In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 479, p. 207-220Article in journal (Refereed)
    Abstract [en]

    In the development of transdermal and topical products it is important to understand how formulation ingredients interact with the molecular components of the upper layer of the skin, the stratum corneum (SC), and thereby influence its macroscopic barrier properties. The aim here was to investigate the effect of two commonly used excipients, transcutol and dexpanthenol, on the molecular as well as the macroscopic properties of the skin membrane. Polarization transfer solid-state NMR methods were combined with steady-state flux and impedance spectroscopy measurements to investigate how these common excipients influence the molecular components of SC and its barrier function at strictly controlled hydration conditions in vitro with excised porcine skin. The NMR results provide completely new molecular insight into how transcutol and dexpanthenol affect specific molecular segments of both SC lipids and proteins. The presence of transcutol or dexpanthenol in the formulation at fixed water activity results in increased effective skin permeability of the model drug metronidazole. Finally, impedance spectroscopy data show clear changes of the effective skin capacitance after treatment with transcutol or dexpanthenol. Based on the complementary data, we are able to draw direct links between effects on the molecular properties and on the macroscopic barrier function of the skin barrier under treatment with formulations containing transcutol or dexpanthenol.

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  • 36.
    Gari, Hala
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Rembiesa, Jadwiga
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Masilionis, Ignas
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Vreda, Naida
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Svensson, Birgitta
    Sund, Torbjörn
    Hansson, Henri
    Morén, Anna Karin
    Sjöö, Malin
    Wahlgren, Marie
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Ruzgas, Tautgirdas
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Amperometric in vitro monitoring of penetration through skin membrane2015In: Electroanalysis, ISSN 1040-0397, E-ISSN 1521-4109, Vol. 27, no 1, p. 111-117Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to demonstrate that penetration of quercetin, hydrogen peroxide and ascorbic acid through skin membranes can be monitored amperometrically. Skin membrane was fixed on the top of chemically modified electrodes and penetration of the appropriate compound was registered as electrode current. The methodology allows the study of penetration from solution as well as from pharmaceutical creams. From realtime measurements of electrode current, fluxes and diffusion coefficients of mentioned compounds in skin membranes have been estimated.

  • 37.
    Rembiesa, Jadwiga
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Gari, Hala
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Ruzgas, Tautgirdas
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Amperometric monitoring of quercetin permeation through skin membranes2015In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 496, no 2, p. 636-643Article in journal (Refereed)
    Abstract [en]

    Transdermal delivery of quercetin (QR, 3,30,40,5,7-pentahydroxyflavone), a natural flavonoid with a considerable antioxidant capacity, is important for medical treatment of, e.g., skin disorders. QR permeability through skin is low, which, at the same time, makes the monitoring of percutaneous QR penetration difficult. The objective of this study was to assess an electrochemical method for monitoring QR penetration through skin membranes. An electrode was covered with the membrane, exposed to QR solution, and electrode current was measured. The registered current was due to electro-oxidation of QR penetrating the membrane. Exploiting strict current-QR flux relationships diffusion coefficient, D, of QR in skin and dialysis membranes was calculated. The D values were strongly dependent on the theoretical model and parameters assumed in the processing of the amperometric data. The highest values of D were in the range of 1.6-6.1 x 10(-7) cm(2)/s. This was reached only for skin membranes pretreated with buffer-ethanol mixture for more than 24 h. QR solutions containing penetration enhancers, ethanol and L-menthol, definitely increased D values. The results demonstrate that electrochemical setup gives a possibility to assess penetration characteristics as well as enables monitoring of penetration dynamics, which is more difficult by traditional methods using Franz cells. (C) 2015 Elsevier B.V. All rights reserved.

  • 38.
    Söderberg, Lars
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Lanbeck, Peter
    Wahlgren, Marie
    Do surface active parenteral formulations cause inflammation?2015In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 484, no 1-2, p. 246-251Article in journal (Refereed)
    Abstract [en]

    Local irritation and inflammation at the site of administration are a common side effect following administration of parenteral formulations. Biological effects of surface (interfacial) activity in solutions are less well investigated than effects caused by other physico-chemical parameters such as pH and osmolality. The interfacial activity in different systems, including human plasma, typical amphiphilic substances with fundamental biological relevance such as free fatty acids, anesthetic depot formulations and six different antibiotics was measured. The relative interfacial pressure, and/or concentration of active substance, required to obtain 50% of the maximal attainable effect in terms of interfacial pressure were calculated. The aim was to test the hypothesis that these parameters would allow comparison to biological effects reported in in vivo studies on the investigated substances. The highest interfacial activity was found in a triglyceride/plasma system. Among the antibiotic tested, the highest interfacial activities were found in erythromycin and dicloxacillin, which is in accordance with previous clinical findings of a high tendency of infusion phlebitis and cell toxicity. Independently of investigated system, biological effects were minimal below a 15% relative increase of interfacial activity. Above 35-45% the effects were severe. Interfacial activity in parenteral formulations may well cause damages to tissues followed by inflammation. (C) 2015 Elsevier B. V. All rights reserved.

  • 39.
    Albèr, Cathrine
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Falkman, Peter
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Kocherbitov, Vitaly
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Hydration of Hyaluronan: Effects on Structural and Thermodynamic Properties2015In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 119, no 11, p. 4211-4219Article in journal (Refereed)
    Abstract [en]

    Hyaluronan (HA) is a frequently occurring biopolymer with a large variety of functions in nature. During the past 60 years, there have been numerous reports on structural and dynamic behavior of HA in water. Nevertheless, studies covering a wider concentration range are still lacking. In this work, we use isothermal scanning sorption calorimetry for the first time to investigate hydration-induced transitions in HA (sodium hyaluronate, 17 kDa). From this method, we obtain the sorption isotherm and the enthalpy and the entropy of hydration. Thermotropic events are evaluated by differential scanning calorimetry (DSC), and structure analysis is performed with X-ray scattering (SWAXS) and light and scanning electron microscopy. During isothermal hydration, HA exhibits a glass transition, followed by crystallization and subsequent dissolution of HA crystals and formation of a one-phase solution. Structural analysis reveals that the crystal may be indexed on an orthorhombic unit cell with space group P212121. Crystallization of HA was found to occur either through endothermic or exothermic processes, depending on the temperature and water content. We propose a mechanism of crystallization that explains this phenomenon based on the interplay between the hydrophobic effect and strengthening of hydrogen bonds during formation of crystals. The combined results were used to construct a binary phase diagram for the HA–water system.

  • 40. Saleem, Shifa
    et al.
    Rosén, Birgitta
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Björkman, Anders
    Improvement of hand sensibility resulting from application of anaesthetic cream on the forearm: importance of dose and time2015In: Hand Therapy, ISSN 1758-9983, E-ISSN 1758-9991, Vol. 20, no 4, p. 109-114Article in journal (Refereed)
    Abstract [en]

    Introduction: A local anaesthetic cream, EMLA (R), applied temporarily to the forearm can improve sensory functions in the hands, both in healthy individuals and in patients with nerve injury. The treatment concept is an example of guided plasticity where the dynamic capacity of the central nervous system is used for therapeutic purposes. However, the optimal dose and duration of the anaesthetic cream is not known and this is addressed here. Methods: Sixty healthy volunteers participated in this experimental study. They were randomised to one of six groups of 10 and received either 10 g or 20 g of EMLA (R) on the volar part of the forearm for either 60, 90 or 120 min, respectively. Outcome measures were touch thresholds and discriminative touch in digits II and V. Results: There was a statistically significant improvement in touch threshold as well as discriminative touch in all six groups. However, there were no statistically significant differences between the six different dose and duration combinations. Conclusions: It is concluded that 10 g of EMLA (R) applied to the volar part of the forearm for 60 min may be adequate to induce improved hand sensibility.

  • 41.
    Runnsjö, Anna
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Gari, Hala
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Ruzgas, Tautgirdas
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö högskola, Biofilms Research Center for Biointerfaces.
    Topical Administration of Mometasone Furoate: A Combined Impedance Spectroscopy and In Vitro Drug Diffusion Study2015In: Journal of Analytical & Pharmaceutical Research, ISSN 2473-0831, Vol. 1, no 1, article id 00004Article in journal (Refereed)
    Abstract [en]

    Mometasone furoate (MF) is a potent steroid for treatment of e.g., eczema and psoriasis. It exerts its function by binding to the glucocorticoid receptors in viable epidermis and dermis. The aim of the current project was to estimate if two clinically equivalent 0.1% MF creams, one w/o (A) and one o/w (B) cream, might impose different systemic load, which is related to adverse side effects. We approached this question by combining analysis of drug permeability in flow through cells and membrane perturbation detected by impedance spectroscopy using excised porcine skin as membranes. We also analyzed the amount of drug that accumulates in the membranes following topical application of the two creams. The results show that both creams generate about the same amount of MF in skin, while cream A generates an order of magnitude higher drug flux through skin. Cream A also caused a twofold increase in the skin dielectric constant (ε), which may be attributed to an increased fluidity of the extracellular lipid matrix in the stratum corneum corresponding to a higher skin permeability. No significant change in skin ε was seen with cream B. To conclude, cream B appears to be the safer alternative as it does not seem to perturb the skin and imposes less systemic burden without sacrificing clinical efficacy

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  • 42.
    Albèr, Cathrine
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Norin, Izabela
    Kocherbitov, Vitaly
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Saleem, Shifa
    Lodén, Marie
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Effects of water activity and low molecular weight humectants on skin permeability and hydration dynamics: a double-blind, randomized and controlled study2014In: International Journal of Cosmetic Science, ISSN 0142-5463, E-ISSN 1468-2494, Vol. 36, no 5, p. 412-418Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The mammalian skin is a barrier that effectively separates the water-rich interior of the body from the normally dryer exterior. Changes in the external conditions, for example ambient humidity, have been shown to affect the skin barrier properties. The prime objective of this study was to evaluate the effect of water activity of a topical formulation on skin hydration and permeability. A second objective was to gain more understanding on how two commonly used humectants, urea and glycerol, affect skin barrier function in vivo. METHODS: Simple aqueous formulations were applied under occlusion to the volar forearm of healthy volunteers. Following 4-h exposure, skin water loss (by transepidermal water loss measurements), skin hydration (by Corneometry) and skin permeability (by time to vasodilation due to benzyl nicotinate exposure) were monitored. RESULTS: The results demonstrate that a relatively small change in the water activity of a topical formulation is sufficient to induce considerable effects on stratum corneum hydration and permeability to exogenous substances. Exposing the skin to high water activity leads to increased skin hydration and also increased permeability. Furthermore, urea and glycerol promote skin hydration and permeability even at reduced water activity of the applied formulation. CONCLUSION: These results highlight the importance of considering the water activity in topically applied formulations and the potential benefit of using humectants. The results may impact formulation optimization in how to facilitate skin hydration and to modify skin permeability by temporarily open and close the skin barrier.

  • 43.
    Fagerström, Anton
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Kocherbitov, Vitaly
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Westbye, Peter
    Bergström, Karin
    Arnebrant, Thomas
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Surfactant softening of plant leaf cuticle model wax: a Differential Scanning Calorimetry (DSC) and Quartz Crystal Microbalance with Dissipation (QCM-D) study2014In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 426, p. 22-30Article in journal (Refereed)
    Abstract [en]

    The aim was to quantify the softening effect that two surfactants (C10EO7 and C8G1.6) have on a plant leaf cuticle model wax. Effects on the thermotropic phase behavior and fluidity of the wax (C22H45OH/C32H66/H2O) were determined. The model wax is crystalline at ambient conditions, yet it is clearly softened by the surfactants. Both surfactants decreased the transition temperatures in the wax and the G″/G' ratio of the wax film increased in irreversible steps following surfactant exposure. C10EO7 has a stronger fluidizing effect than C8G1.6 due to stronger interaction with the hydrophobic waxes. Intracuticular waxes (IW) comprise both crystalline and amorphous domains and it has previously been proposed that the fluidizing effects of surfactants are due to interactions with the amorphous parts. New data suggests that this may be a simplification. Surfactants may also absorb in crevices between crystalline domains. This causes an irreversible effect and a softer cuticle wax.

  • 44.
    Fagerström, Anton
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Kocherbitov, Vitaly
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Westbye, Peter
    Bergström, Karin
    Mamontova, Varvara
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Characterization of a plant leaf cuticle model wax, phase behaviour ofmodel wax-water systems2013In: Thermochimica Acta, ISSN 0040-6031, E-ISSN 1872-762X, Vol. 571, p. 42-52Article in journal (Refereed)
    Abstract [en]

    We investigated the thermotropic phase behavior of plant leaf intracuticular wax and two representatives of its main components, 1-docosanol (C22H45OH) and dotriacontane (C32H66), in dry and hydrated state. One objective was to obtain a model wax, which can be used to estimate formulations effects on cuticle diffusivity in vitro. The two wax components were chosen based on results from Gas Chromatography coupled to Mass Spectrometry analysis of cuticular wax. The wax was extracted from Clivia Miniata Regel leaves and contained 68% primary alcohols (C16-C32) and 16% n-alkanes (C21-C33). Differential Scanning Calorimetry, Polarized light microscopy and Small- and Wide Angle X-ray Diffraction were used to characterize the cuticular extract and the phase behaviour of the C22H45OH/C32H66/H2O model system. Four individual crystalline phases were discovered in the model wax – water system and eutectic melting occurred in both dry and hydrated state. The thermotropic transitions of the model wax occur within the broader transition region of the extracted leaf wax.

  • 45.
    Fagerström, Anton
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Kocherbitov, Vitaly
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Westbye, Peter
    Bergström, Karin
    Mamontova, Varvara
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Composition of plant leaf wax, phase behavior of major components and effects of hydration2013In: Proceedings of the 10th International Symposium on Adjuvants for Agrochemicals (ISAA 2013), ISAA Society , 2013, p. 257-262Conference paper (Other academic)
    Abstract [en]

    The aim of this project was to characterize thermotropic phase behavior and morphology of major wax components of a plant leaf cuticle in dry and hydrated conditions. The composition of the cuticular wax from adaxial leaves of the plant Clivia Miniata Regel was characterized by GC-MS. The analysis showed that the wax is dominated by aliphatic compounds, mainly alkanes (C22-C33) and alcohols (C16-C32). Based on this analysis a model wax was composed comprising 1-docosanol (C22H45OH) and dotriacontane (C32H66). The simplicity of the model allowed for a thorough physical-chemical analysis of the system. Differential Scanning Calorimetry (DSC) and Small Angle X-ray Diffraction (SAXD) were employed to map the phase behavior and morphology of the C22H45OH/C32H66/H2O system. In dry stateC22H45OH and C32H66 observe eutectic interaction with substantial changes in the melting temperatures. C32H66 transforms to a second crystalline phase just below the eutectic point.C32H66 do not interact with water but C22H45OH forms a hydrate with a conformational change in hydrocarbon chain packing. Long chain alcohols is a major component in cuticular wax of many plant species and their ability to form hydrates with less ordered chain conformation can add to the understanding of the nature and barrier function of the plant leaf cuticle.

  • 46.
    Fagerström, Anton
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Kocherbitov, Vitaly
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Ruzgas, Tautgirdas
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Westbye, Peter
    Bergström, Karin
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Effects of surfactants and thermodynamic activity of model active ingredient on transport over plant leaf cuticle2013In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 103, p. 572-579Article in journal (Refereed)
    Abstract [en]

    The main objective of this study was to investigate the mechanism of molecular transport across the cuticle of Clivia leaves. In vitro diffusion methodology was used to investigate the transport of a systemic fungicide, tebuconazole, over a model silicone membrane, enzymatically isolated cuticle membranes, and dermatomed leaves. It was shown that dermatomed leaves may replace enzymatically isolated cuticles. Furthermore, the effects of two surfactants, C10EO7 and C8G1.6, on the fungicide transport were investigated. Tebuconazole cuticle permeation was described using Fick's first law of diffusion, expressed by the thermodynamic activity of the solute in the membrane. A new method for calculation of diffusion coefficients in the membrane is proposed. To access the thermodynamic activity of the fungicide in the membranes, sorption isotherms of tebuconazole in the membrane materials studied were recorded. The thermodynamic activity of the fungicide in aqueous solutions was calculated from solubility data. For that purpose, the effect of surfactants on tebuconazole solubility was studied. The results show that addition of surfactants allows for higher concentrations of tebuconazole available for penetration. Nonetheless, at a fixed fungicide thermodynamic activity, all formulations produced the same flux over the silicone membrane independently on the fungicide concentration. This shows that the driving force across non-responding membranes is the gradient of thermodynamic activity, rather than the gradient of the fungicide concentration. In case of leaves, surfactants induced the same quantitative increase in both flux and diffusion coefficient of solute in the cuticle, while the cuticle-water partition coefficient was unaffected.

  • 47.
    Albèr, Cathrine
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Brandner, Birgit
    Björklund, Sebastian
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Billsten, Peter
    Corkery, Robert
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Effects of water gradients and use of urea on skin ultrastructure evaluated by confocal Raman microspectroscopy2013In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1828, no 11, p. 2470-2478Article in journal (Refereed)
    Abstract [en]

    The rather thin outermost layer of the mammalian skin, stratum corneum (SC), is a complex biomembrane which separates the water rich inside of the body from the dry outside. The skin surface can be exposed to rather extreme variations in ambient conditions (e.g. water activity, temperature and pH), with potential effects on the barrier function. Increased understanding of how the barrier is affected by such changes is highly relevant for regulation of transdermal uptake of exogenous chemicals. In the present study we investigate the effect of hydration and the use of a well-known humectant, urea, on skin barrier ultrastructure by means of confocal Raman microspectroscopy. We also perform dynamic vapor sorption (DVS) microbalance measurements to examine the water uptake capacity of SC pretreated with urea. Based on novel Raman images, constructed from 20 spectral maps, we can distinguish large water inclusions within the skin membrane exceeding the size of fully hydrated corneocytes. We show that these inclusions contain water with spectral properties similar to that of bulk water. The results furthermore show that the ambient water activity has an important impact on the formation of these water inclusions as well as on the hydration profile across the membrane. Urea significantly increases the water uptake when present in skin, as compared to skin without urea, and it promotes formation of larger water inclusions in the tissue. The results confirm that urea can be used as a humectant to increase skin hydration.

  • 48.
    Björklund, Sebastian
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Thuresson, Krister
    Sparr, Emma
    Glycerol and urea can be used to increase skin permeability in reduced hydration conditions2013In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 5, no 50, p. 638-645Article in journal (Refereed)
    Abstract [en]

    The natural moisturizing factor (NMF) is a group of hygroscopic molecules that is naturally present in skin and protects from severe drying. Glycerol and urea are two examples of NMF components that are also used in skin care applications. In the present study, we investigate the influence of glycerol and urea on the permeability of a model drug (metronidazole, Mz) across excised pig skin membranes at different hydrating conditions. The degree of skin hydration is regulated by the gradient in water activity across the membrane, which in turn depends on the water activity of the formulation in contact with the skin membrane. Here, we determine the water activity of all formulations employed using an isothermal calorimetric method. Thus, the gradient in water activity is controlled by a novel experimental set-up with well-defined boundary conditions on both sides of the skin membrane. The results demonstrate that glycerol and urea can retain high steady state flux of Mz across skin membranes at dehydrating conditions, which otherwise would decrease the permeability due to dehydration. X-ray diffraction measurements are performed to give insight into the effects of glycerol and urea on SC molecular organization. The novel steady state flux results can be related to the observation that water, glycerol, and urea all affect the structural features of the SC molecular components in a similar manner.

  • 49.
    Björklund, Sebastian
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Ruzgas, Tautgirdas
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Nowacka, Agnieszka
    Dahi, Ihab
    Topgaard, Daniel
    Spaar, Emma
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Skin membrane electrical impedance properties under the influence of a varying water gradient2013In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 104, no 12, p. 2639-2650Article in journal (Refereed)
    Abstract [en]

    The stratum corneum (SC) is an effective permeability barrier. One strategy to increase drug delivery across skin is to increase the hydration. A detailed description of how hydration affects skin permeability requires characterization of both macroscopic and molecular properties and how they respond to hydration. We explore this issue by performing impedance experiments on excised skin membranes in the frequency range 1 Hz to 0.2 MHz under the influence of a varying gradient in water activity (aw). Hydration/dehydration induces reversible changes of membrane resistance and effective capacitance. On average, the membrane resistance is 14 times lower and the effective capacitance is 1.5 times higher when the outermost SC membrane is exposed to hydrating conditions (aw ¼ 0.992), as compared to the case of more dehydrating conditions (aw ¼ 0.826). Molecular insight into the hydration effects on the SC components is provided by natural-abundance 13C polarization transfer solidstate NMR and x-ray diffraction under similar hydration conditions. Hydration has a significant effect on the dynamics of the keratin filament terminals and increases the interchain spacing of the filaments. The SC lipids are organized into lamellar structures with ~ 12.6 nm spacing and hexagonal hydrocarbon chain packing with mainly all-trans configuration of the acyl chains, irrespective of hydration state. Subtle changes in the dynamics of the lipids due to mobilization and incorporation of cholesterol and long-chain lipid species into the fluid lipid fraction is suggested to occur upon hydration, which can explain the changes of the impedance response. The results presented here provide information that is useful in explaining the effect of hydration on skin permeability.

  • 50. Wahlgren, Marie
    et al.
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Sjoo, Malin
    Rayner, Marilyn
    The Use of Micro- and Nanoparticles in the Stabilisation of Pickering-Type Emulsions for Topical Delivery2013In: Current Pharmaceutical Biotechnology, ISSN 1389-2010, E-ISSN 1873-4316, Vol. 14, no 15, p. 1222-1234Article in journal (Refereed)
    Abstract [en]

    This review describes the use of Pickering emulsions for topical drug delivery. The focus is on Pickering emulsions and how to formulate these. However, a short description of the challenges of topical drug delivery is also given. The article describes how Pickering emulsions might have other properties than traditional topical creams. It is our believe that Pickering emulsions could give added value to topical formulations as it is surfactant free, has new properties, and may alter the transport of drugs across the skin barrier.

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