Effect of self-microemulsifying drug delivery systems containing Labrasol on tight junctions in Caco-2 cells.
The aim of this study was to investigate the effect of two novel self-microemulsifying drug delivery systems (SMEDDS) containing Labrasol with different dilutions on tight junctions. Changes in barrier properties of Caco-2 cell monolayers, including transepithelial electrical resistance (TEER) and permeability to the paracellular marker, i.e., mannitol, were assessed in response to dilutions and surfactants contents within formulations. The cytotoxicity of SMEDDS and the effect of surfactants on Caco-2 cells were evaluated by the MTT. Changes in subcellular localization of the tight junction proteins, ZO-1 and F-actin, were examined by confocal laser scanning microscopy. Results demonstrated that negatively charged SMEDDS with different dilutions had no effect on the TEER, but significantly increased the permeability of mannitol. In contrast, the positively charged formulation showed a dilution-dependent reduction in TEER. A corresponding increase in mannitol permeability of up to 29.4-fold to 64.7-fold greater than the control was also observed across the monolayer. Labrasol with the concentration of 0.1 and 1% was shown to increase the permeability of mannitol by 4.6-fold and 33.8-fold, respectively. The mechanism of opening of tight junctions was found to involve F-actin-related changes and redistribution of ZO-1.
Sha
Xianyi
X
Department of Pharmaceutics, School of Pharmacy, Fudan University, No. 138 Yixueyuan Road, Shanghai 200032, China. shaxianyi89@hotmail.com
Yan
Guijun
G
Wu
Yunjuan
Y
Li
Junchan
J
Fang
Xiaoling
X
D000199:Actins / Q000032:analysis; D018938:Caco-2 Cells; D016503:Drug Delivery Systems; D017097:Electric Impedance; D004655:Emulsions / Q000008:administration & dosage*; D005989:Glycerides; D006801:Humans; D008353:Mannitol / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis; D009930:Organic Chemicals; D010750:Phosphoproteins / Q000032:analysis; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
D000199:Actins; D004655:Emulsions; D005989:Glycerides; D008565:Membrane Proteins; D009930:Organic Chemicals; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C440220:Labrasol; D008353:Mannitol