Development and mechanistic study of a microemulsion containing vitamin E TPGS for the enhancement of oral absorption of celecoxib

Abstract

Purpose: The purpose of this study was to develop a microemulsion containing D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) as a biodegradable surfactant to increase the oral absorption of celecoxib. Methods: This study investigated the intestinal absorption enhancement mechanism of this microemulsion by measuring transepithelial electrical resistance (TEER) values. This study also evaluated microemulsion particle–intestine interactions in terms of release and attachment processes using confocal laser scanning microscopy (CLSM). Results: The prepared microemulsion particles had a size of <300 nm with a neutral surface charge. The celecoxib-loaded microemulsion release kinetic was classified as the zero-order model. This vitamin E TPGS-based microemulsion significantly increased the in vitro intestinal absorption of celecoxib compared to celecoxib solution. The CLSM study suggested that microemulsion particles with entrapped drugs might attach to the intestinal epithelium before releasing the entrapped drug into tissues. The TEER value of the intestinal tissues treated with the celecoxib-loaded microemulsion was significantly decreased compared to the value before treatment, indicating an increase in drug transport via the paracellular pathway. The evaluation of intestinal tissue cytotoxicity using lactate dehydrogenase cytotoxicity assay suggested that the prepared celecoxib-loaded microemulsion was safe for oral route administration. Conclusions: The prepared celecoxib loaded microemulsion could increase the intestinal absorption of celecoxib compared to celecoxib solution. The intestinal absorption enhancement mechanism of this microemulsion resulted from the increase of the drug transport via the paracellular pathway.