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Falkman, Peter
Publications (10 of 17) Show all publications
Campos Pacheco, J. E., Yalovenko, T., Riaz, A., Kotov, N., Davids, C., Persson, A., . . . Valetti, S. (2024). Inhalable porous particles as dual micro-nano carriers demonstrating efficient lung drug delivery for treatment of tuberculosis. Journal of Controlled Release, 369, 231-250, Article ID S0168-3659(24)00165-2.
Open this publication in new window or tab >>Inhalable porous particles as dual micro-nano carriers demonstrating efficient lung drug delivery for treatment of tuberculosis
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2024 (English)In: 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) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
Clofazimine, Disordered mesoporous silica particles, Dissolution enhancement, Dried powder formulation, Dual micro-nano carrier, Lung drug delivery, Soluble carrier
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:mau:diva-66943 (URN)10.1016/j.jconrel.2024.03.013 (DOI)001219489000001 ()38479444 (PubMedID)2-s2.0-85189001903 (Scopus ID)
Available from: 2024-04-26 Created: 2024-04-26 Last updated: 2024-05-23Bibliographically approved
Campos Pacheco, J. E., Riaz, A., Falkman, P., Feiler, A., Ekström, M., Pilkington, G. & Valetti, S. (2023). Encapsulation of clofazimine in mesoporous silica as a potential dry powder formulation for treating tuberculosis. Journal of Aerosol Medicine, 36(6), A13-A13, Article ID A13.
Open this publication in new window or tab >>Encapsulation of clofazimine in mesoporous silica as a potential dry powder formulation for treating tuberculosis
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2023 (English)In: Journal of Aerosol Medicine, ISSN 1941-2711, E-ISSN 1941-2703, Vol. 36, no 6, p. A13-A13, article id A13Article in journal, Meeting abstract (Other academic) Published
National Category
Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:mau:diva-66242 (URN)001126390700043 ()
Available from: 2024-03-07 Created: 2024-03-07 Last updated: 2024-06-18Bibliographically approved
Digaitis, R., Falkman, P., Oltner, V., Briggner, L.-E. & Kocherbitov, V. (2022). Hydration and dehydration induced changes in porosity of starch microspheres. Carbohydrate Polymers, 291, 119542-119542, Article ID 119542.
Open this publication in new window or tab >>Hydration and dehydration induced changes in porosity of starch microspheres
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2022 (English)In: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 291, p. 119542-119542, article id 119542Article in journal (Refereed) Published
Abstract [en]

Characterization and tuning of the porosity of amorphous starch materials are important for many applications, including controlled release of encapsulated proteins. The porosities of these materials in dry and hydrated states can have different physicochemical origins and properties. Here, porosities of dry cross-linked starch microspheres and their hydration-induced transformations were characterized by small angle X-ray scattering, scanning electron and optical microscopies, thermogravimetric analysis, sorption calorimetry, nitrogen sorption, and helium-pycnometry. The analyses revealed that dry microspheres consist of porous cores with pore diameters below 100 nm and shells which appeared to be denser but contained wider pores (100–300 nm). The outer crust of the microspheres shell is non-porous, which restricts diffusion of nitrogen, water, and ethanol. Partial hydration triggered an irreversible collapse of dry porosity at 12 wt% water. Further hydration resulted in interfacial changes and promoted wet porosity, related to characteristic distances between polymer chains.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
Degradable starch microspheres, Cross-linking, Dry porosity, Wet porosity, Water sorption
National Category
Paper, Pulp and Fiber Technology
Identifiers
urn:nbn:se:mau:diva-53308 (URN)10.1016/j.carbpol.2022.119542 (DOI)000798768400007 ()35698372 (PubMedID)2-s2.0-85129672134 (Scopus ID)
Available from: 2022-06-21 Created: 2022-06-21 Last updated: 2024-02-05Bibliographically approved
Ali, A., Ringstad, L., Skedung, L., Falkman, P., Wahlgren, M. & Engblom, J. (2022). Tactile friction of topical creams and emulsions: Friction measurements on excised skin and VitroSkin® using ForceBoard™.. International Journal of Pharmaceutics, 615, Article ID 121502.
Open this publication in new window or tab >>Tactile friction of topical creams and emulsions: Friction measurements on excised skin and VitroSkin® using ForceBoard™.
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2022 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 615, article id 121502Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
Excised skin, Force-Board™, Pickering emulsions, Surfactant-free formulations, Tactile friction, Topical creams, VitroSkin®
National Category
Food Engineering
Identifiers
urn:nbn:se:mau:diva-50117 (URN)10.1016/j.ijpharm.2022.121502 (DOI)000781015400004 ()35091002 (PubMedID)2-s2.0-85123703718 (Scopus ID)
Available from: 2022-02-14 Created: 2022-02-14 Last updated: 2024-02-05Bibliographically approved
Valetti, S., Thomsen, H., Wankar, J., Falkman, P., Manet, I., Feiler, A., . . . Engblom, J. (2021). Can mesoporous nanoparticles promote bioavailability of topical pharmaceutics?. International Journal of Pharmaceutics, 602, Article ID 120609.
Open this publication in new window or tab >>Can mesoporous nanoparticles promote bioavailability of topical pharmaceutics?
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2021 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 602, article id 120609Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2021
Keywords
dermal drug delivery, multiphoton microscopy, nanoparticles, skin topography, targeted delivery
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:mau:diva-42122 (URN)10.1016/j.ijpharm.2021.120609 (DOI)000657606400004 ()33901597 (PubMedID)2-s2.0-85105266815 (Scopus ID)
Available from: 2021-05-07 Created: 2021-05-07 Last updated: 2024-02-05Bibliographically approved
Yang, Y., Wu, Z., Chen, X., Huang, Y., Wu, B., Falkman, P. & Sunden, B. (2020). Transport dynamics of droplet impact on the wedge-patterned biphilic surface. Experimental Thermal and Fluid Science, 113, Article ID 110020.
Open this publication in new window or tab >>Transport dynamics of droplet impact on the wedge-patterned biphilic surface
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2020 (English)In: Experimental Thermal and Fluid Science, ISSN 0894-1777, E-ISSN 1879-2286, Vol. 113, article id 110020Article in journal (Refereed) Published
Abstract [en]

Droplet impact on biphilic surfaces with a wettability contrast has been intensively studied in recent years. In this work the effects of tilting and apex angles on droplet transport dynamics after impacting on a wedge-patterned biphilic surface at low Weber numbers were investigated experimentally. The biphilic surface was fabricated by applying a hydrophobic polymer coating on a bare silicon surface. According to the experimental results, a larger apex angle below 67.4 degrees can accelerate the droplet effectively at first. Then the friction force controls the droplet movement and reduces the speed. The tilting angle along the hydrophilic direction activates the droplet. If the gravity component is opposite to the hydrophilic direction and the tilting angle is over 15 degrees, the droplet can hardly move toward the hydrophilic area. By modeling the hydrodynamics of the droplet movement after impact on a biphilic surface with assumptions of no evaporation, no Marangoni effect, negligible dynamic contact angle variation and negligible rotation effect, the surface tension values versus the position at different apex angles are derived. The predicted position versus time trends agree well with the experimental data. This study aims to provide a better understanding of the mechanisms of droplet hydrodynamics on wedge-patterned biphilic surfaces at low Weber numbers.

Place, publisher, year, edition, pages
Elsevier, 2020
National Category
Fluid Mechanics and Acoustics
Identifiers
urn:nbn:se:mau:diva-13793 (URN)10.1016/j.expthermflusci.2019.110020 (DOI)000515424000010 ()2-s2.0-85076684556 (Scopus ID)
Available from: 2020-03-17 Created: 2020-03-17 Last updated: 2024-06-17Bibliographically approved
Ali, A., Wahlgren, M., Rembratt-Svensson, B., Daftani, A., Falkman, P., Wollmer, P. & Engblom, J. (2019). Dehydration affects drug transport over nasal mucosa (ed.). Drug Delivery, 26(1), 831-840
Open this publication in new window or tab >>Dehydration affects drug transport over nasal mucosa
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2019 (English)In: Drug Delivery, ISSN 1071-7544, E-ISSN 1521-0464, Vol. 26, no 1, p. 831-840Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
Mucoadhesion, dehydration, drug transport, nasal drug delivery, water activity
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:mau:diva-15215 (URN)10.1080/10717544.2019.1650848 (DOI)000480247200001 ()31401887 (PubMedID)2-s2.0-85071047269 (Scopus ID)29688 (Local ID)29688 (Archive number)29688 (OAI)
Available from: 2020-03-30 Created: 2020-03-30 Last updated: 2024-02-05Bibliographically approved
Wu, Z., Pham, A. D., Cao, Z., Albèr, C., Falkman, P., Ruzgas, T. & Sunden, B. (2019). Pool boiling heat transfer of n -pentane and acetone on nanostructured surfaces by electrophoretic deposition. In: Proceedings of the Asme International Mechanical Engineering Congress and Exposition, 2018, vol 8b: . Paper presented at ASME International Mechanical Engineering Congress and Exposition (IMECE2018), Pittsburgh, PA, NOV 09-15, 2018. Amer Soc Mechanical Engineers
Open this publication in new window or tab >>Pool boiling heat transfer of n -pentane and acetone on nanostructured surfaces by electrophoretic deposition
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2019 (English)In: Proceedings of the Asme International Mechanical Engineering Congress and Exposition, 2018, vol 8b, Amer Soc Mechanical Engineers , 2019Conference paper, Published paper (Refereed)
Abstract [en]

This work aims to investigate pool boiling heat transfer enhancement by using nanostructured surfaces. Two types of nanostructured surfaces were employed, gold nanoparticlecoated surfaces and alumina nanoparticle-coated surfaces. The nanostructured surfaces were fabricated by an electrophoretic deposition technique, depositing nanoparticles in a nanofluid onto smooth copper surfaces under an electric field. N -pentane and acetone were tested as working fluids. Compared to the smooth surface, the pool boiling heat transfer coefficient has been increased by 80% for n -pentane and acetone. Possible mechanisms for the enhancement in heat transfer are qualitatively provided. The increase in active nucleation site density due to multiple micro/nanopores on nanoparticle-coated surfaces is likely the main contributor. The critical heat flux on nanostructured surfaces are approximately the same as that on the smooth surface because both smooth and modified surfaces show similar wickability for the two working fluids.

Place, publisher, year, edition, pages
Amer Soc Mechanical Engineers, 2019
Keywords
boiling, nanostructured surface, electrophoretic deposition, heat transfer coefficient, well-wetting liquid
National Category
Materials Chemistry
Identifiers
urn:nbn:se:mau:diva-39995 (URN)10.1115/IMECE2018-87752 (DOI)000465191800061 ()2-s2.0-85063985247 (Scopus ID)978-0-7918-5212-5 (ISBN)
Conference
ASME International Mechanical Engineering Congress and Exposition (IMECE2018), Pittsburgh, PA, NOV 09-15, 2018
Available from: 2021-01-26 Created: 2021-01-26 Last updated: 2024-04-04Bibliographically approved
Cao, Z., Zan, W., Pham, A.-D., Yang, Y., Abbood, S., Falkman, P., . . . Sundén, B. (2019). Pool boiling of HFE-7200 on nanoparticle-coating surfaces: Experiments and heat transfer analysis (ed.). International Journal of Heat and Mass Transfer, 133, 548-560
Open this publication in new window or tab >>Pool boiling of HFE-7200 on nanoparticle-coating surfaces: Experiments and heat transfer analysis
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2019 (English)In: International Journal of Heat and Mass Transfer, ISSN 0017-9310, E-ISSN 1879-2189, Vol. 133, p. 548-560Article in journal (Refereed) Published
Abstract [en]

In the present study, an electrophoretic deposition method was employed to modify copper surfaces with Cu-Zn (∼100 nm) nanoparticles. Pool boiling heat transfer of HFE-7200 on the modified surfaces was experimentally studied. The results showed that the heat transfer coefficient on the modified surfaces was significantly enhanced compared with that on a smooth surface, e.g., a maximum 100% enhancement, while the maximum superheat on the modified surfaces was around 20 K lower than that on the smooth surface. However, the critical heat flux (CHF) was not improved considerably, and supplementary tests indicated that the wickability of HFE-7200 was almost the same on the modified surfaces and the smooth surface. The departure diameters of bubbles were recorded by a high speed camera, which were compared with several models in literature. Active nucleation site sizes were evaluated by the Hsu nucleation theory and active nucleation site densities were estimated by appropriate correlations. In addition, a heat transfer model, considering natural convection, re-formation of thermal boundary layer and microlayer evaporation, was formulated to predict the heat transfer on the modified surfaces and the smooth surface. A relatively good prediction was achieved.

Place, publisher, year, edition, pages
Elsevier, 2019
National Category
Natural Sciences
Identifiers
urn:nbn:se:mau:diva-4455 (URN)10.1016/j.ijheatmasstransfer.2018.12.140 (DOI)000460710100047 ()2-s2.0-85059134443 (Scopus ID)30750 (Local ID)30750 (Archive number)30750 (OAI)
Available from: 2020-02-28 Created: 2020-02-28 Last updated: 2024-06-17Bibliographically approved
Danielsson, R., Svensson, A., Falkman, P. & Eriksson, H. (2018). Tracing Aluminium-based Adjuvants: Their Interactions with Immune Competent Cells and their Effect on Mitochondrial Activity (ed.). Open Immunology Journal, 8, 1-15
Open this publication in new window or tab >>Tracing Aluminium-based Adjuvants: Their Interactions with Immune Competent Cells and their Effect on Mitochondrial Activity
2018 (English)In: Open Immunology Journal, ISSN 1874-2262, Vol. 8, p. 1-15Article in journal (Refereed)
Abstract [en]

Background: Studies revealing the immune stimulatory properties of aluminium-based adjuvants (ABAs) have been impaired by the absence of simple and reliable methods of tracing the adjuvants and their effect on biochemical processes upon endocytosis. Objective: To verify that labelling of ABAs with lumogallion doesn’t affect the physicochemical properties of the adjuvant; tracing cellular interaction with aluminium adjuvants; explore their effect on metabolic activity upon endocytosis. Methods: Physicochemical characterization by Z-potential and size distribution of ABAs labelled with lumogallion. Cellular interactions with ABAs by flow cytometry and confocal microscopy. Metabolic activity explored by measuring transformation of tetrazolium into formazan. Results: No or minor change of zeta potential and average particle size of lumogallion labelled aluminium oxyhydroxide, AlO(OH) and aluminium hydroxyphosphate, Al(OH)x(PO4 )y. Both phagocytosing and non-phagocytosing leukocytes became associated with ABAs at concentrations expected after in vivo administration of a vaccine. The ABAs were relatively toxic, affecting both lymphocytes and monocytes, and Al(OH)x(PO4 )y was more toxic than AlO(OH). Endocytosed aluminium adjuvant particles were not secreted from the cells and remained intracellular throughout several cell divisions. The presence of ABAs increased the mitochondrial activity of the monocytic cell line THP-1 and peripheral monocytes, as based on the transformation of tetrazolium into formazan. Conclusion: Lumogallion labelled ABAs is a valuable tool tracing interactions between ABAs and cells. Labelled ABAs can be traced intracellularly and ABAs are likely to remain intracellular for a long period of time. Intracellular ABAs increase the mitochondrial activity and the presence of intracellular Al ions is suggested to cause an increased mitochondrial activity. Keywords: Aluminium based adjuvant, Lumogallion, Mitochondrial activity, MTT assay, Phagocytosis, ABAS, Zeolites.

Place, publisher, year, edition, pages
Bentham eBooks, 2018
Keywords
Aluminium based adjuvant, Lumogallion, Mitochondrial activity, MTT assay, Phagocytosis, ABAS, Zeolites
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:mau:diva-5015 (URN)10.2174/1874226201808010001 (DOI)26775 (Local ID)26775 (Archive number)26775 (OAI)
Available from: 2020-02-28 Created: 2020-02-28 Last updated: 2022-12-07Bibliographically approved
Projects
Pickering emulsions on skin: Effects of ethanol prior to, during and after application at different ambient conditions; Malmö UniversityNon-invasive monitoring of skin disorders progression and healing – a low molecular weight biomarker approach; Malmö UniversityThe effect of the extracellular lipid organisation on skin barrier function; Malmö University, Biofilms Research Center for Biointerfaces
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