Insulin-S.O (sodium oleate) complex-loaded PLGA nanoparticles: formulation, characterization and in vivo evaluation.

ABSTRACT

S.O (sodium oleate) is an anionic surfactant, which is able to forman ionic complex with positively charged insulin at suitable pH. In a previous study, the insulin-S.O (Ins-S.O) complex was prepared by a hydrophobic ion pairing (HIP) method to improve the apparent liposolubility of insulin. The formation of the complex was further confirmed by Zeta potential and X-ray method. Based on the preliminary study, poly(lactide-co-glycolide) (PLGA) nanoparticles harbouring Ins-S.O complex was prepared via an emulsion solvent diffusion method. The effects of key parameters such as concentration of PVA, concentration of PLGA and initial-loaded drug on the properties of the nanoparticles were investigated. The insulin encapsulation efficiency (EE(%)) reached up to 91.2% and mean diameter of the nanoparticles was sized approximately 160 nm under optimal conditions. The pharmacological effects of the nanoparticles made of PLGA (75/25, Av Mw 15,000) were further evaluated to confirm their potential suitability for oral delivery. In order to evaluate hyperglycaemic effect of the nanoparticles for oral administration, Ins-S.O complex-loaded PLGA nanoparticles (20 IU/Kg) were administered orally by force-feeding to diabetic rats. In the case of the nanoparticles, the plasma glucose level reduced to 23.85% from the initial one 12 h post-administration and this continued for 24 h. The results showed that the use of Ins-S.O complex-loaded PLGA nanoparticles is an effective method of reducing plasma glucose levels. The insulin nanoparticles also improved the glycaemic response to an oral glucose challenge.