Abstract
Membrane destabilizing properties and increased efflux of doxorubicin from liposomes caused by basic butylated methacrylate copolymer (BBMC), better known under its commercial trade name EUDRAGIT E, have been described in the scientific literature. Here, we investigated the effect of BBMC on suspended and filter-grown Caco2 cells with respect to apical-to-basal transport and membrane permeabilization using transport assays, trypan blue exclusion assay, measurements of transepithelial electrical resistance (TEER), confocal laser scanning microscopy, and transmission electron microscopy. The effect of inhibiting protein phosphatase 2A (PP2A) by okadaic acid was investigated by measuring TEER, but a link between PP2A and the observed effects could not be established. Overall, membrane permeabilization of Caco2 cells by BBMC was demonstrated, which went along with increased apical-to-basal transport of the model compounds mannitol, talinolol, and trospium. The effect was concentration- and time-dependent, and reversible. Enhancement occurred at polymer concentrations as low as 20 microg/mL.
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