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Enhancing Oral Bioavailability by Paclitaxel Polymeric Micelles: Role of Transmembrane Pathways in the Oral Absorption.

The oral administration of paclitaxel suffering obstacles like poorly solubility and low permeability, causing extremely low oral bioavailability. In this study, we aim to study the role of transmembrane pathway on the absorption mechanisms of PTX-Micelles. In addition, we will further study the permeability of PTX-Micelles by employing in situ perfusion model. The results showed the PTX-Micelles could be up taken by caco-2 intact. In addition, we found that the endocytosis pathway and M cells pathway attended, while paracellular pathway absented in the transport process of PTX-Micelles. The study on in situ perfusion showed the absorption rate constant (Ka) of PTX was enhanced from 6.3, 6.1, 10.6 and 13.6 × 10-2/min to 15.1, 18.4, 45.6 and 42.9 × 10-2/min by micelles in duodenum, jejunum, ileum and colon, respectively, indicating the PTX-Micelles could enhance the permeability of PTX in intestinal membrane. This study indicating that transmembrane pathway-mediated transport is an important part in the transport process of polymeric micelles, and designing formulation based on transmembrane pathways may be a promising route for oral bioavailability enhancement of poor-soluble drugs.