Effect of PLGA hydrophilia on the drug release and the hypoglucemic activity of different insulin-loaded PLGA microspheres

The effects of viscosity and hydrophilic characteristics of different PLGA polymers on the microencapsulation of insulin have been studied in vitro and in vivo after subcutaneous administration to hyperglycemic rats. Hydrophilic PLGA polymers produced a higher burst effect than the hydrophobic ones. Moreover, an incomplete insulin release was observed with the hydrophilic PLGA polymers in comparison with the hydrophobic ones. An explanation for that incomplete release can be the development of polymer-insulin interactions associated to the polymer hydrophilic/hydrophobic character, as detected by DSC analysis. Differences in the release rate of microsphere formulations lead to differences in the hypoglycemic action and the weight of animals. Hydrophobic PLGA was able to prolong the hypoglycemic action up to 4 weeks which is at least double than that obtained with hydrophilic PLGA of a similar viscosity. Comparing insulin microspheres with an immediate release formulation, microspheres can increase insulin relative bioavailability up to four times.