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  • 1. Albrecht, Karin
    et al.
    Greindl, Melanie
    Deutel, Britta
    Kremser, Christian
    Wolf, Christian
    Talasz, Heribert
    Stollenwerk, Maria Magdalena
    Debbage, Paul
    Bernkop-Schnürch, Andreas
    In Vivo Investigation of Thiomer-Polyvinylpyrrolidon Nanoparticles Using Magnetic Resonance Imaging2010In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 99, no 4, p. 2008-2017Article in journal (Refereed)
    Abstract [en]

    This study focused on the investigation of the permeation enhancing effects of a stomach targeted, nanoparticulate drug delivery system. The polyacrylic acid–cysteine/polyvinylpyrrolidon nanoparticles were loaded with the magnetic resonance imaging (MRI) contrast agent diethylenetriaminepentaacetic acid gadolinium( III)dihydrogen salt (Gd-DTPA). Average particle size was determined to be 130nm and the optimum for stability was found to be below a pH of 4.5. In vitro permeation studies were performed on rat gastric mucosa and revealed an eightfold increase in Gd- DTPA uptake when incorporated in the nanoparticles compared to evaluation in the presence of unformulated polyacrylic acid–cysteine. In vivo investigations with rats were performed via the noninvasive MRI method in order to track the nanoparticles way through the gastrointestinal tract. When Gd-DTPA was administered orally as nanoparticulate suspension, an increased MRI signal in the urinary bladder was detected after 34 min, providing evidence for systemic uptake and renal elimination of the contrast agent. As control experiments with Gd-DTPA only or in combination with unformulated polyacrylic acid–cysteine revealed no MRI signal increase at all, the significant permeation enhancing effect could be identified based on the nanoparticulate formulation.

  • 2.
    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.

  • 3.
    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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  • 4.
    Campos Pacheco, Jesús Enrique
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Yalovenko, Tetiana
    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.
    Kotov, Nikolay
    Department of Chemistry, KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden.
    Davids, Camilla
    Department of Microbiology, Immunology and Glycobiology, Institution of Laboratory Medicine, Lund University, Lund, Sweden.
    Persson, Alva
    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.
    Feiler, Adam
    Godaly, Gabriela
    Department of Microbiology, Immunology and Glycobiology, Institution of Laboratory Medicine, Lund University, Lund, Sweden.
    Johnson, C Magnus
    Department of Chemistry, KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden.
    Ekström, Mikael
    Iconovo AB, Ideongatan 3A-B, 223 70 Lund, Sweden.
    Pilkington, Georgia A
    Department of Chemistry, KTH Royal Institute of Technology, SE-100 44 Stockholm, Sweden; Nanologica AB (publ), Forskargatan 20G, 151 36 Södertälje, Sweden.
    Valetti, Sabrina
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Inhalable porous particles as dual micro-nano carriers demonstrating efficient lung drug delivery for treatment of tuberculosis2024In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 369, p. 231-250, article id S0168-3659(24)00165-2Article in journal (Refereed)
    Abstract [en]

    Inhalation therapy treating severe infectious disease is among the more complex and emerging topics in controlled drug release. Micron-sized carriers are needed to deposit drugs into the lower airways, while nano-sized carriers are of preference for cell targeting. Here, we present a novel and versatile strategy using micron-sized spherical particles with an excellent aerodynamic profile that dissolve in the lung fluid to ultimately generate nanoparticles enabling to enhance both extra- and intra-cellular drug delivery (i.e., dual micro-nano inhalation strategy). The spherical particles are synthesised through the condensation of nano-sized amorphous silicon dioxide resulting in high surface area, disordered mesoporous silica particles (MSPs) with monodispersed size of 2.43 μm. Clofazimine (CLZ), a drug shown to be effective against multidrug-resistant tuberculosis, was encapsulated in the MSPs obtaining a dry powder formulation with high respirable fraction (F.P.F. <5 μm of 50%) without the need of additional excipients. DSC, XRPD, and Nitrogen adsorption-desorption indicate that the drug was fully amorphous when confined in the nano-sized pores (9-10 nm) of the MSPs (shelf-life of 20 months at 4 °C). Once deposited in the lung, the CLZ-MSPs exhibited a dual action. Firstly, the nanoconfinement within the MSPs enabled a drastic dissolution enhancement of CLZ in simulated lung fluid (i.e., 16-fold higher than the free drug), increasing mycobacterial killing than CLZ alone (p = 0.0262) and reaching concentrations above the minimum bactericidal concentration (MBC) against biofilms of M. tuberculosis (i.e., targeting extracellular bacteria). The released CLZ permeated but was highly retained in a Calu-3 respiratory epithelium model, suggesting a high local drug concentration within the lung tissue minimizing risk for systemic side effects. Secondly, the micron-sized drug carriers spontaneously dissolve in simulated lung fluid into nano-sized drug carriers (shown by Nano-FTIR), delivering high CLZ cargo inside macrophages and drastically decreasing the mycobacterial burden inside macrophages (i.e., targeting intracellular bacteria). Safety studies showed neither measurable toxicity on macrophages nor Calu-3 cells, nor impaired epithelial integrity. The dissolved MSPs also did not show haemolytic effect on human erythrocytes. In a nutshell, this study presents a low-cost, stable and non-invasive dried powder formulation based on a dual micro-nano carrier to efficiently deliver drug to the lungs overcoming technological and practical challenges for global healthcare.

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  • 5.
    Eriksson, Tommy
    Lunds universitet.
    Apotekaren, receptarien och klinisk farmaci: utbildning, utveckling, utmaningar och behov av kraftsamling för att bli samhällets läkemedelsexperter2014Report (Other academic)
    Abstract [sv]

    Den farmaceutiska professionen håller snabbt på att förändras och våra lärosäten är inte tillräckligt snabba i sina omställningar för att möte nya behov i samhället. Det behövs ökad tydlighet av vad receptarie- respektive apotekarkompetensen, professionerna och yrkena inkluderar. Vetenskapsområdet farmaci behöver alltså diskuteras och uppdateras. Kompetens inom naturvetenskaper som kemi och biologi är självklart nödvändigt för apotekare och även för receptarier men detta är stödjande kompetenser inte kärnkompetenser.

    Jag har skrivit denna bok för att dela med mig av min resa och erfarenheter för att etablera farmacin som en viktig komponent i patientvården och i vårdteamet runt patienten för bättre läkemedelsanvändning. Denna roll har varit intressant för studenter och yrkesverksamma under flera decennier men har inte fått genomslag i grundutbildningarna. Under min resa har jag fått kompetenser och erfarenheter inom kemi, farmaci, farmakologi, läkemedelsutveckling, farmakoterapi, evidensbaserad medicin, klinisk farmaci och pedagogik, som praktiker, produkt-, tjänste- och verksamhetsutvecklare, lärare och utbildningsansvarig, akademiker, forskare och internationell expert till myndigheter och organisationer, som beskrivs i författarpresentationen.

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  • 6.
    Eriksson, Tommy
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Midlöv, PatrikLunds universitet.
    Farmakologi och farmakoterapi2023Collection (editor) (Other academic)
    Abstract [sv]

    Ordination av läkemedel börjar oftast hos en läkare och då inleds en komplex process där flera olika professioner, framför allt sjuksköterskor och farmaceuter, bidrar med sin kompetens till en helhetssyn för att optimera läkemedelsbehandling. Detta är fokus i denna bok, Farmakologi och farmakoterapi. Här presenteras den teoretiska bakgrunden som ger förståelse i hur läkemedel omsätts och fungerar i kroppen, men även farmakoterapi (läkemedelsbehandling) och vanliga läkemedelsrelaterade problem beskrivs. Boken är uppdelad i tre delar. Den första delen beskriver olika aspekter på praktisk läkemedelsanvändning i vården och av patienten. Speciellt fokus läggs på utvärdering av läkemedelsbehandling och samarbete mellan vårdens olika professioner. Den andra delen beskriver basalfarmakologiska principer och tillämpningar där teori och praktiska utföranden varvas. Del tre är uppbyggd enligt ATC-systemet och fokuserar på farmakoterapi vid olika sjukdomstillstånd där rekommendationer samt nytta och eventuella risker med läkemedel beskrivs. Boken vänder sig till studenter på sjuksköterskeprogrammet och till yrkesverksamma sjuksköterskor. Den kan även användas av andra professioner inom hälso- och sjukvården, såväl i undervisning som i informationssökande.

  • 7.
    Eriksson, Tommy
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Polidori, Carlo
    Univ Camerino, Expt Med & Publ Hlth, Camerino, MC, Italy..
    The Granada Statements: An opportunity for the hospital pharmacist to make more impact in the publication world, part 22023In: European journal of hospital pharmacy. Science and practice, ISSN 2047-9956, E-ISSN 2047-9964, Vol. 30, no 6, p. 309-309Article in journal (Other academic)
  • 8.
    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
    Scherer, Dieter
    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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  • 9.
    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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  • 10.
    Girelli, Anita
    et al.
    nstitut für Angewandte Physik, Universität Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany.
    Beck, Christian
    nstitut für Angewandte Physik, Universität Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany; Institut Laue-Langevin, 71 Avenue des Martyrs, 38042 Grenoble, France.
    Bäuerle, Famke
    nstitut für Angewandte Physik, Universität Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany.
    Matsarskaia, Olga
    Institut Laue-Langevin, 71 Avenue des Martyrs, 38042 Grenoble, France.
    Maier, Ralph
    nstitut für Angewandte Physik, Universität Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany.
    Zhang, Fajun
    nstitut für Angewandte Physik, Universität Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany.
    Wu, Baohu
    Jülich Centre for Neutron Science JCNS at MLZ, Forschungszentrum Jülich, Lichtenbergstraße 1, 85748 Garching, Germany.
    Lang, Christian
    Jülich Centre for Neutron Science JCNS at MLZ, Forschungszentrum Jülich, Lichtenbergstraße 1, 85748 Garching, Germany.
    Czakkel, Orsolya
    Institut Laue-Langevin, 71 Avenue des Martyrs, 38042 Grenoble, France.
    Seydel, Tilo
    Institut Laue-Langevin, 71 Avenue des Martyrs, 38042 Grenoble, France.
    Schreiber, Frank
    nstitut für Angewandte Physik, Universität Tübingen, Auf der Morgenstelle 10, 72076 Tübingen, Germany.
    Roosen-Runge, Felix
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Molecular Flexibility of Antibodies Preserved Even in the Dense Phase after Macroscopic Phase Separation2021In: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 18, no 11, p. 4162-4169Article in journal (Refereed)
    Abstract [en]

    Antibody therapies are typically based on high-concentration formulations that need to be administered subcutaneously. These conditions induce several challenges, inter alia a viscosity suitable for injection, sufficient solution stability, and preservation of molecular function. To obtain systematic insights into the molecular factors, we study the dynamics on the molecular level under strongly varying solution conditions. In particular, we use solutions of antibodies with poly(ethylene glycol), in which simple cooling from room temperature to freezing temperatures induces a transition from a well-dispersed solution into a phase-separated and macroscopically arrested system. Using quasi-elastic neutron scattering during in situ cooling ramps and in prethermalized measurements, we observe a strong decrease in antibody diffusion, while internal flexibility persists to a significant degree, thus ensuring the movement necessary for the preservation of molecular function. These results are relevant for a more dynamic understanding of antibodies in high-concentration formulations, which affects the formation of transient clusters governing the solution viscosity.

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  • 11.
    Hallan, Supandeep Singh
    et al.
    Malmö University, Biofilms Research Center for Biointerfaces. Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Department of Chemical and Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara, Italy.
    Sguizzato, Maddalena
    Department of Chemical and Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara, Italy.
    Drechsler, Markus
    Bavarian Polymerinstitute “Electron and Optical Microscopy”, University of Bayreuth, D-95440 Bayreuth, Germany.
    Mariani, Paolo
    Department of Life and Environmental Sciences, Polytechnic University of Marche, I-60131 Ancona, Italy.
    Montesi, Leda
    Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara, Italy.
    Cortesi, Rita
    Department of Chemical and Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara, Italy.
    Björklund, Sebastian
    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).
    Esposito, Elisabetta
    Department of Chemical and Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara, Italy.
    The Potential of Caffeic Acid Lipid Nanoparticulate Systems for Skin Application: In Vitro Assays to Assess Delivery and Antioxidant Effect2021In: Nanomaterials, E-ISSN 2079-4991, Vol. 11, no 1, article id E171Article in journal (Refereed)
    Abstract [en]

    The object of this study is a comparison between solid lipid nanoparticles and ethosomes for caffeic acid delivery through the skin. Caffeic acid is a potent antioxidant molecule whose cutaneous administration is hampered by its low solubility and scarce stability. In order to improve its therapeutic potential, caffeic acid has been encapsulated within solid lipid nanoparticles and ethosomes. The effect of lipid matrix has been evaluated on the morphology and size distribution of solid lipid nanoparticles and ethosomes loaded with caffeic acid. Particularly, morphology has been investigated by cryogenic transmission electron microscopy and small angle X-ray scattering, while mean diameters have been evaluated by photon correlation spectroscopy. The antioxidant power has been evaluated by the 2,2-diphenyl-1-picrylhydrazyl methodology. The influence of the type of nanoparticulate system on caffeic acid diffusion has been evaluated by Franz cells associated to the nylon membrane, while to evaluate caffeic acid permeation through the skin, an amperometric study has been conducted, which was based on a porcine skin-covered oxygen electrode. This apparatus allows measuring the O2 concentration changes in the membrane induced by polyphenols and H2O2 reaction in the skin. The antioxidative reactions in the skin induced by caffeic acid administered by solid lipid nanoparticles or ethosomes have been evaluated. Franz cell results indicated that caffeic acid diffusion from ethosomes was 18-fold slower with respect to solid lipid nanoparticles. The amperometric method evidenced the transdermal delivery effect of ethosome, indicating an intense antioxidant activity of caffeic acid and a very low response in the case of SLN. Finally, an irritation patch test conducted on 20 human volunteers demonstrated that both ethosomes and solid lipid nanoparticles can be safely applied on the skin.

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  • 12.
    Hussain, Nayab
    Malmö University, Faculty of Health and Society (HS).
    OPTIMIZING DRUG DELIVERY PREDICTABILITY FROM INTRAVAGINAL RINGS: THE ROLE OF TEMPERATURE AND SURFACTANTS2024Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
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  • 13.
    Moeller, Kim
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Criminology (KR).
    Svensson, Bengt
    Malmö University, Faculty of Health and Society (HS), Department of Social Work (SA).
    "Shop Until You Drop": Valuing Fentanyl Analogs on a Swedish Internet Forum2021In: Journal of Drug Issues, ISSN 0022-0426, E-ISSN 1945-1369, Vol. 51, no 1, p. 181-195, article id 0022042620964129Article in journal (Refereed)
    Abstract [en]

    Fentanyl analogs are synthetic opioids used for pain treatment and palliative care, which are also sought after by drug users for their psychoactive properties. Clandestinely produced fentanyl has caused an overdose crises of unprecedented scale in the United States. In Sweden, the retail purchase, possession, and use of some analogs are legal, providing opiate users with a legal alternative, until the process of scheduling is finished. The continuous process of scheduling and introduction of slightly modified variants implies that there is much uncertainty regarding the potency and quality of newly introduced analogs. We examine user perceptions of fentanyl analogs in a thematic analysis of the public internet forum, Flashback, from 2012 to 2019. In 24 threads on fentanyl analogs, posters shared and discussed information on the emergence of new analogs, their desirability and prices, adverse health effects, and eventual scheduling.

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  • 14.
    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
    Anderson, Christopher D
    Ollmar, Stig
    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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  • 15.
    Polidori, Carlo
    et al.
    Experimental medicine and Public health, University of Camerino, Camerino, Italy.
    Eriksson, Tommy
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    The Granada Statements: an impact boost to clinical and social pharmacy publications, part 12023In: European journal of hospital pharmacy. Science and practice, ISSN 2047-9956, E-ISSN 2047-9964, Vol. 30, no 4, p. 187-187Article in journal (Other academic)
  • 16.
    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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  • 17.
    Riaz, Azra
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Gidvall, Sanna
    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).
    Hernandez, Aura Rocio
    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.
    Nilsson, Emelie J.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Davies, Julia R
    Malmö University, Faculty of Odontology (OD). 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.
    Three-Dimensional Oral Mucosal Equivalents as Models for Transmucosal Drug Permeation Studies2023In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 15, no 5, p. 1513-1513Article in journal (Refereed)
    Abstract [en]

    Oral transmucosal administration, where drugs are absorbed directly through the non-keratinized, lining mucosa of the mouth, represents a solution to drug delivery with several advantages. Oral mucosal equivalents (OME) developed as 3D in vitro models are of great interest since they express the correct cell differentiation and tissue architecture, simulating the in vivo conditions better than monolayer cultures or animal tissues. The aim of this work was to develop OME to be used as a membrane for drug permeation studies. We developed both full-thickness (i.e., connective plus epithelial tissue) and split-thickness (i.e., only epithelial tissue) OME using non-tumor-derived human keratinocytes OKF6 TERT-2 obtained from the floor of the mouth. All the OME developed here presented similar transepithelial electrical resistance (TEER) values, comparable to the commercial EpiOral™. Using eletriptan hydrobromide as a model drug, we found that the full-thickness OME had similar drug flux to EpiOral™ (28.8 vs. 29.6 µg/cm2/h), suggesting that the model had the same permeation barrier properties. Furthermore, full-thickness OME showed an increase in ceramide content together with a decrease in phospholipids in comparison to the monolayer culture, indicating that lipid differentiation occurred due to the tissue-engineering protocols. The split-thickness mucosal model resulted in 4–5 cell layers with basal cells still undergoing mitosis. The optimum period at the air–liquid interface for this model was twenty-one days; after longer times, signs of apoptosis appeared. Following the 3R principles, we found that the addition of Ca2+, retinoic acid, linoleic acid, epidermal growth factor and bovine pituitary extract was important but not sufficient to fully replace the fetal bovine serum. Finally, the OME models presented here offer a longer shelf-life than the pre-existing models, which paves the way for the further investigation of broader pharmaceutical applications (i.e., long-term drug exposure, effect on the keratinocytes’ differentiation and inflammatory conditions, etc.).

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  • 18.
    Svensson, Olof
    et al.
    Malmö högskola, Faculty of Health and Society (HS).
    Thuresson, Krister
    Arnebrant, Thomas
    Malmö högskola, Faculty of Health and Society (HS).
    Interactions between chitosan-modified particles and mucin-coated surfaces2008In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 2, no 325, p. 346-350Article in journal (Refereed)
    Abstract [en]

    Lipid-based particles (Cubosome® particles) were surface-modified by chitosan and the ratio between particles and chitosan was optimized to minimize the free chitosan concentration in the dispersion. The modified particles were characterized by electrophoretic measurements and the pH dependence of the zeta potential could be directly related to the protonation of chitosan. Interaction between the modified particles and mucin-coated silica surfaces were subsequently investigated in situ by ellipsometry to assess the mucoadhesive properties at physiologically relevant conditions. The result showed that a substantial amount of modified particles was adsorbed to mucin-coated silica surfaces at both pH 4 and pH 6, probably due to electrostatic interactions between amino groups in chitosan and negatively charged groups in mucin. Furthermore, the amount of bound particles decreased by less than 15% upon rinsing indicating relatively strong interactions. This investigation demonstrates that ellipsometry is a useful tool to study mucoadhesive properties of particles in the submicrometer range. Moreover, the novel chitosan-modified particles may be of interest for mucosal drug delivery applications.

  • 19.
    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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  • 20.
    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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  • 21.
    Westerlund, Tommy
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Apoteket AB, Sweden.
    Söderlund, Lars-Åke
    International Pharmaceutical Federation, The Hague, the Netherlands..
    Role of community pharmacy and pharmacists in self care in Sweden2023In: Exploratory research in clinical and social pharmacy, ISSN 2667-2766, Vol. 12, article id 100362Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Self care is an important concept, which is increasingly being applied by policy makers on a large scale. It is associated with improved health literacy and technological advances. Community pharmacy practitioners are easily accessible for self care counselling, purchase of non-prescription products and for referrals to other healthcare providers.

    OBJECTIVE: To describe self care policies and strategies in Swedish healthcare authorities, pharmaceutical organizations and community pharmacy.

    METHODS: A search was conducted to retrieve self care policy documents and strategies in Swedish healthcare authorities, pharmaceutical organizations and community pharmacy on respective websites, as well as personal contacts with key persons in pharmaceutical organizations and community pharmacy practice.

    RESULTS: A new law on self care was adopted by the Swedish Parliament becoming effective in 2023. The law defines self care as a healthcare measure that has been assessed by a treating licenced healthcare practitioner to be possible to be performed by the patient him/herself. The law includes a wide range of measures. According to a Government Commission that followed Sweden's the National Pharmaceutical Strategy's Action Plan in 2018, the Medical Products Agency (MPA) was assigned to establish requirements of qualifications in self care counselling. In its report in late 2022, the MPA stated that self care counselling by community pharmacy practitioners plays an important role in society. The new requirements are expected to become effective in mid-2023. None of the four community pharmacy chains operating 97% of Sweden's community pharmacies have developed any specific self care policies, although self care counselling and sales of non-prescription products, as well as provision of some primary healthcare services, constitute important components of their operations. Furthermore, all Swedish pharmacies offer several digital self care solutions, supporting people to manage their own health. Neither the Swedish Pharmacy Association, representing most pharmacies, nor the Swedish Pharmacists Association, the trade union, have developed any self care policies. However, the Swedish Association of the Pharmaceutical Industry is promulgating Swedish self care reform using a systematic review of self care and which medicines should be over-the-counter.

    CONCLUSIONS: Self care is not currently established as a core pillar of a Swedish national health strategy. There are further opportunities to enable pharmacists to fulfil their potential in supporting individual wellbeing and promoting self care interventions. A new system needs to be created which fully integrates the promotion of everyday wellbeing, self care for self-treatable conditions and the management of long-term conditions.

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