A kind of polymeric lipid vesicles (PLVs) with pH-responsive turning on-off membrane for programed delivery of insulin in gastrointestinal (GI) tract was developed, which was self-assembled from the grafted amphipathic polymer of N-tocopheryl-N'-succinyl-ɛ-poly-l-lysine (TP/SC-g-PLL). By controlling the grafting ratio of hydrophobic alkane and ionizable carboxyl branches, the permeability of membrane was adjustable and thus allowing insulin release in a GI-pH dependent manner. The effects of grafting degree of substitution (DS) on the pH-responsive behavior of the formed vesicles were confirmed by critical aggregation concentration determination, morphology and size characterization. Their transepithelial permeability across the GI tract was proved by both confocal visualization in vitro model of Caco-2 cellular monolayer and in vivo hypoglycemic study in diabetic rats. Accordingly, the work described here indicated that the self-assembled PLVs could be a promising candidate for improving the GI delivery of hydrophilic biomacromolecule agents.
Keywords: Vesicle; cellular uptake; insulin; pH-responsive; self-assembly; transport.