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壳聚糖包封调节辣椒素对MDCK细胞紧密连接的作用。

Chitosan encapsulation modulates the effect of capsaicin on the tight junctions of MDCK cells.

作者信息

Kaiser M, Pereira S, Pohl L, Ketelhut S, Kemper B, Gorzelanny C, Galla H-J, Moerschbacher B M, Goycoolea F M

机构信息

Institute of Plant Biology and Biotechnology (IBBP), Westfälische Wilhelms-Universität Münster, Schlossgarten 3, Münster 48149, Germany.

Biomedical Technology Center of the Medical Faculty, Westfälische Wilhelms-Universität Münster, Mendelstraße 17, Münster 48149, Germany.

出版信息

Sci Rep. 2015 May 13;5:10048. doi: 10.1038/srep10048.

DOI:10.1038/srep10048
PMID:25970096
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4429556/
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.

摘要

辣椒素具有多种已知的药理作用，其中包括能够可逆地打开细胞紧密连接。本研究的目的是开发一种策略，通过使用由辣椒素和壳聚糖组成的纳米系统可逆地打开细胞紧密连接，来增强低渗透性物质（异硫氰酸荧光素 - 葡聚糖）跨上皮细胞单层的细胞旁转运。我们比较了游离辣椒素和载辣椒素壳聚糖纳米胶囊的生物物理性质，包括它们对上皮MDCK - C7细胞的细胞毒性以及对紧密连接完整性、膜通透性和细胞摄取的影响。游离化合物在浓度为500 μM时对MDCK - C7细胞有明显的细胞毒性反应，但包封后未观察到这种反应。通过阻抗谱、数字全息显微镜和结构光照荧光显微镜研究了纳米胶囊与MDCK - C7细胞紧密连接之间的相互作用。纳米胶囊调节了辣椒素与紧密连接之间的相互作用，这表现为跨上皮电阻的不同时间变化曲线以及与异硫氰酸荧光素 - 葡聚糖孵育的单层膜通透性增强。结构光照荧光显微镜显示纳米胶囊被MDCK - C7细胞内化。载辣椒素纳米胶囊可进一步开发为具有增强上皮通透性的药物纳米载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8260/4429556/3a216e308da7/srep10048-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8260/4429556/636813f2760b/srep10048-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8260/4429556/39a4f7566497/srep10048-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8260/4429556/3e32f224219a/srep10048-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8260/4429556/476acd68fc84/srep10048-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8260/4429556/3f6cd0d01b97/srep10048-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8260/4429556/91c04ce08207/srep10048-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8260/4429556/3a216e308da7/srep10048-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8260/4429556/636813f2760b/srep10048-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8260/4429556/39a4f7566497/srep10048-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8260/4429556/3e32f224219a/srep10048-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8260/4429556/476acd68fc84/srep10048-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8260/4429556/3f6cd0d01b97/srep10048-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8260/4429556/91c04ce08207/srep10048-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8260/4429556/3a216e308da7/srep10048-f7.jpg

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