Targeted folate-conjugated pluronic P85/poly(lactide-co-glycolide) polymersome for the oral delivery of insulin.

Aim: To explore the better efficacy of targeted folic acid (FA)-Pluronic 85-poly(lactide-co-glycolide) (FA-P85-PLGA) polymersome in oral insulin delivery.

Materials & Methods: The cytotoxicity of the polymers, in vitro qualitative and quantitative cellular uptake and the internalization mechanism of insulin-loaded FA-P85-PLGA and PLGA-P85-PLGA polymersomes were studied with the human colon adenocarcinoma cells (Caco-2 cells). Their pharmacodynamics and pharmacokinetics properties were also studied with diabetic rats.

Results & Conclusion: Polymersomes have shown good biocompatibility. Polymersomes are mainly localized within the cytoplasm of Caco-2 cells from fluorescence microscopy images. FA-P85-PLGA exhibited higher cellular uptake than PLGA-P85-PLGA polymersomes and free fluorescein isothiocyanate-labeled insulin (FITC-insulin) did. The uptake process of targeted polymersomes included clathrin- and caveolae-mediated endocytosis, macropinocytosis and the folate receptor-mediated endocytosis. Insulin-loaded FA-P85-PLGA showed better hypoglycemic effects than insulin-loaded PLGA-P85-PLGA.