Malmö University Publications
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  • 1.
    Björklund, Sebastian
    et al.
    Malmö högskola, Faculty of Health and Society (HS).
    Engblom, Johan
    Malmö högskola, Faculty of Health and Society (HS).
    Thuresson, Krister
    Sparr, Emma
    A water gradient can be used to regulate drug transport across skin2010In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 143, no 2, p. 191-200Article in journal (Refereed)
    Abstract [en]

    At normal conditions there is a substantial water gradient over the skin as it separates the water-rich inside of the body from the dry outside. This leads to a variation in the degree of hydration from the inside to the outside of skin and changes in this gradient may affect its structure and function. In this study we raise the question: How do changes in the water gradient across skin affect its permeability? We approach this problem in novel diffusion experiments that permit strict control of the gradient in the chemical potential of water and hence well-defined boundary conditions. The results demonstrate that a water gradient can be used to regulate transport of drugs with different lipophilic characteristics across the skin barrier. It is shown that the transport of metronidazole (log Po/w=0.0) and methyl salicylate (log Po/w=2.5) across skin increases abruptly at low water gradients, corresponding to high degrees of skin hydration, and that this effect is reversible. This phenomenon is highly relevant to drug delivery applications due to its potential of temporarily open the skin barrier for transdermal drug delivery and subsequently close the barrier after treatment. Further, the results contribute to the understanding of the occlusion effect and indicate the boundary conditions of the water gradient needed to make use of this effect

  • 2.
    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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  • 3.
    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.
    Boutonnet, Marine
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Svensson, Birgitta
    Butler, Eile
    Lood, Rolf
    Blom, Kristina
    Vallejo, Bibiana
    Anderson, Chris
    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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  • 4. Pham, Quoc Dat
    et al.
    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
    Sparr, Emma
    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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