Preparation and Characterization of Polymeric Nanoparticles for Sustained Delivery of Insulin

The present study was aimed at developing and exploring a novel sustained release formulation of PEGylated insulin encapsulated in polymeric nanoparticles that produces prolonged insulin release. The insulin was conjugated with PEG-2000 at specific amino terminus of its B chain. PEGylated insulin was encapsulated in PLGA nanoparticles made by double emulsification method. Insulin conformation and antidiabetic activity were retained after PEGylation and PLGA encapsulation. The nano-spherical particles revealed a low burst release, an important safety feature for an extended release insulin product. In PBS (pH 7.4) at 37oC, formulations with drug content of approximately 14.4% showed very low initial release of insulin over one day and near zero order drug release after a lag of 2-3 days. For animal studies, PLGA nanoparticles loaded with PEGylated insulin were administered subcutaneously as a single injection and produced a release of 15% insulin in the first day but then lowered the serum glucose levels of diabetic rats to values <200 mg/dL for approximately 2 days. Based on these findings, it is suggested that the novel PEG–insulin encapsulated PLGA nanoparticles can be used as a carrier for prolonged and sustained release insulin formulation.