title: Chitosan encapsulation modulates the effect of capsaicin on the tight junctions of MDCK cells.
abstract: Capsaicin has known pharmacological effects including the ability to reversibly open cellular tight junctions, among others. The aim of this study was to develop a strategy to enhance the paracellular transport of a substance with low permeability (FITC-dextran) across an epithelial cell monolayer via reversible opening of cellular tight junctions using a nanosystem comprised by capsaicin and of chitosan. We compared the biophysical properties of free capsaicin and capsaicin-loaded chitosan nanocapsules, including their cytotoxicity towards epithelial MDCK-C7 cells and their effect on the integrity of tight junctions, membrane permeability and cellular uptake. The cytotoxic response of MDCK-C7 cells to capsaicin at a concentration of 500 μM, which was evident for the free compound, is not observable following its encapsulation. The interaction between nanocapsules and the tight junctions of MDCK-C7 cells was investigated by impedance spectroscopy, digital holographic microscopy and structured illumination fluorescence microscopy. The nanocapsules modulated the interaction between capsaicin and tight junctions as shown by the different time profile of trans-epithelial electrical resistance and the enhanced permeability of monolayers incubated with FITC-dextran. Structured illumination fluorescence microscopy showed that the nanocapsules were internalized by MDCK-C7 cells. The capsaicin-loaded nanocapsules could be further developed as drug nanocarriers with enhanced epithelial permeability.
authors.affiliation: Institute of Plant Biology and Biotechnology (IBBP), Westfälische Wilhelms-Universität Münster, Schlossgarten 3, Münster 48149, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Kaiser
authors.affiliation: Institute of Plant Biology and Biotechnology (IBBP), Westfälische Wilhelms-Universität Münster, Schlossgarten 3, Münster 48149, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Pereira
authors.affiliation: Biomedical Technology Center of the Medical Faculty, Westfälische Wilhelms-Universität Münster, Mendelstraße 17, Münster 48149, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Pohl
authors.affiliation: Biomedical Technology Center of the Medical Faculty, Westfälische Wilhelms-Universität Münster, Mendelstraße 17, Münster 48149, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Ketelhut
authors.affiliation: Biomedical Technology Center of the Medical Faculty, Westfälische Wilhelms-Universität Münster, Mendelstraße 17, Münster 48149, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Kemper
authors.affiliation: Experimental Dermatology, Department of Dermatology, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Gorzelanny
authors.affiliation: Institute for Biochemistry, Westfälische Wilhelms-Universität Münster, Wilhelm Klemm Straße 2, Münster 48149, Germany.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Galla
authors.affiliation: Institute of Plant Biology and Biotechnology (IBBP), Westfälische Wilhelms-Universität Münster, Schlossgarten 3, Münster 48149, Germany.
authors.forename: B M
authors.initials: BM
authors.lastname: Moerschbacher
authors.affiliation: Institute of Plant Biology and Biotechnology (IBBP), Westfälische Wilhelms-Universität Münster, Schlossgarten 3, Münster 48149, Germany.
authors.forename: F M
authors.initials: FM
authors.lastname: Goycoolea
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage*; D002214:Capsules / Q000737:chemistry; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry; D065546:Drug Liberation; D004655:Emulsions / Q000737:chemistry; D036103:Nanotechnology; D010539:Permeability; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D002214:Capsules; D004655:Emulsions; D048271:Chitosan; D002211:Capsaicin