Construction and characterization of intestinal oligopeptide transporter PepT1-targeted polymeric micelles for enhanced intestinal absorption of poorly water-soluble agents.

To overcome the main barrier of intestinal epithelium for the oral absorption of poorly water-soluble drugs and further improve their oral absorption, Gly-Sar, the substrate of the oligopeptide transporter PepT1 widely distributed in the small intestine, conjugated poly(ethylene glycol)-block-poly(D,L-lactide) (Gly-Sar-PEG-b-PLA) was designed and synthesized, and PepT1-targeted polymeric micelles were prepared and characterized. The structure of the synthesized Gly-Sar-PEG-b-PLA was confirmed by use of TLC and 1H-NMR. The average molecular weight measured by GPC was 5954 g/mol with PDI of 1.34. The DiI-loaded polymeric micelles from Gly-Sar-PEG-b-PLA with drug loading content of 0.076% were characterized to exhibit 40.36 nm in diameter with PDI of 0.294, and well-defined spherical shape observed by TEM. Furthermore, the PepT1-targeted polymeric micelles profoundly enhanced intestinal absorption of poorly water-soluble drug. Therefore, the designed PepT1-targeted polymeric micelles might have a promising potential for oral delivery of water-insoluble drugs. [ABSTRACT FROM AUTHOR]