Synthesis and Evaluation of Hydrophobically- Modified Polysaccharides as Oral Delivery Vehicles for Poorly Water-Soluble Drugs

摘要

Novel polysaccharide-based micelles were prepared to exploit their potential towards solubilizing poorly water-soluble drugs in order to improve their oral bioavailability. Hydrophobically-modified (HM) dextran (DEX) and hydroxypropylcellulose (HPC) copolymers were synthesized. Cyclosporine A (CsA) was selected as a model drug. In aqueous solution, HM-DEX and HM-HPC form polymeric micelles with low onset of micellization. The CsA incorporation in HM-polysaccharide micelles was significantly higher than in corresponding unmodified polysaccharides. The polymeric micelles exhibited no significant cytotoxicity towards Caco-2 cells at concentrations up to 10 g/L. The apical to basal permeability of CsA across Caco-2 cells increased significantly, when loaded in polymeric micelles, compared to free CsA.