Effect of process variables on formulation, in-vitro characterisation and subcutaneous delivery of insulin PLGA nanoparticles: An optimisation study

Abstract

This study was initiated to investigate the effect of PLGA concentration, PVA concentration, internal to external phase ratio (IEPR), PEG molecular weight and concentration on mean particle size, zeta potential, polydispersity index (PDI), percentage drug entrapment and in vitro release profile. Using PLGA (50:50) as the carrier, insulin nanoparticles (NP) were prepared using double emulsion solvent evaporation technique. The particle size was analysed by dynamic light scattering (DLS) and the geometrical shape was examined using scanning electron microscopy (SEM). Mean particle size was highly dependent on the combined effect of PLGA and PVA concentrations. Drug entrapment would be greatly controlled by PLGA concentration and internal to external phase ratio. Addition of PEG could modulate in vitro release behavior of insulin with initial burst at the first 12 h and sustain the drug release for 6 days. Insulin integrity was assessed in vitro using MALDI-TOF mass spectroscopy. The optimised NP formulation, had particle size of 202.60 nm and percent entrapment efficiency (EE) equal to 67.72%, was tested in vivo to examine its hypoglycemic effect after subcutaneous injection. Insulin NP had a significant hypoglycemic effect comparing to free insulin (p < 0.01) and insulin zinc suspension (p < 0.05).