OBJECTIVETo prepare insulin-loaded polymeric nanoparticles based on polyethyleneimine-polycaprolactone- polyethylene glycol-polycaprolactone-polyethyleneimine pentablock copolymers and evaluate its in vitro release of insulin.

METHODSPolycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) triblock copolymer was synthesized by ring-opening polymerization method, and the pentablock copolymer was prepared by Michael addition reaction. The copolymers obtained were characterized by Fourier-transform infrared (FT-IR) spectroscopy and (1)H-NMR and their critical aggregation concentration (CAC) was measured by fluorescence technique with pyrene as the probe. Insulin-loaded polymeric nanoparticles based on the pentablock copolymers were prepared by solvent evaporation method that exploited the cationic nature of PEI-PCL-PEG-PCL-PEI to allow the formation of ionic complexes with anionic biomolecules such as insulin. The prepared nanoparticles were further characterized by Malvern laser particle sizer and transmittion electron microscopy (TEM). The drug loading, encapsulation efficiency and in vitro release profile of the nanoparticles were analyzed using Bradford method.

RESULTSUsing copolymer PEI10K-PCL4K-PEG2K-PCL4K-PEI10K as the drug carrier, the spherical nanoparticles prepared with an optimal insulin-coplymer mass ratio of 40% allowed the maximum insulin loading of (18.63∓0.07)% and had an average particle size of 175.30∓19.51 nm. The prepared nanoparticles was capable of sustained release of insulin for as long as 48 h in vitro, and the burst release could be minimized by incorporation of PEI in the triblock copolymer.

CONCLUSIONThe insulin-loaded polymeric nanoparticles based on the pentablock copolymers allow sustained release of insulin in vitro, and PEI can enhance sustained drug release and reduce burst drug release.