Folate-decorated PLGA nanoparticles as a rationally designed vehicle for the oral delivery of insulin

The present study reports a novel approach for enhancing the oral absorption and hypoglycemic activity of insulin via encapsulation in folate-(FA) coupled polyethylene glycol (PEG)ylated polylactide-co-glycolide (PLGA) nanoparticles (NPs; FA-PEG-PLGA NPs). Materials & methods: Insulin-loaded FA-PEG-PLGA NPs (size similar to 260 nm; insulin loading similar to 6.5% [w/w]; encapsulation efficiency: 87.0 +/- 1.92%) were prepared by double-emulsion solvent evaporation method. The bioavailability and hypoglycemic activity of orally administered FA-insulin NPs were studied in diabetic rats. Results & conclusion: FA-PEG-PLGA NPs (50 U/kg) exhibited a twofold increase in the oral bioavailability (double hypoglycemia) without any hypoglycemic shock as compared to subcutaneously administered standard insulin solution. Insulin NPs maintained a continual blood glucose level for 24 h, which, however, was transient (<8 h) in the case of subcutaneous insulin and associated with severe hypoglycemic shock. Overall, we have developed a patient-compliant, oral nanoformulation of insulin, once-daily administration of which would be sufficient to control diabetes for at least 24 h. Original submitted 16 November 2011; Revised submitted 2 February 2012; Published online 14 May 2012