Effect of poly(ethylene glycol) content and formulation parameters on particulate properties and intraperitoneal delivery of insulin from PLGA nanoparticles prepared using the double-emulsion evaporation procedure

Context Size, encapsulation efficiency and stability affect the sustained release from nanoparticles containing protein-type drugs.Objectives Insulin was used to evaluate effects of formulation parameters on minimising diameter, maximising encapsulation efficiency and preserving blood glucose control following intraperitoneal (IP) administration. Methods Homogenisation or sonication was used to incorporate insulin into poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles with increasing PEG content. Effects of polymer type, insulin/polymer loading ratio and stabiliser in the internal aqueous phase on physicochemical characteristics of NP, in vitro release and stability of encapsulated insulin were investigated. Entrapment efficiency and release were assessed by radioimmunoassay and bicinconnic acid protein assay, and stability was evaluated using SDS-PAGE. Bioactivity of insulin was assessed in streptozotocin-induced, insulin-deficient Type I diabetic mice.Results Increasing polymeric PEG increased encapsulation efficiency, whilst absence of internal stabiliser improved encapsulation and minimised burst release kinetics. Homogenisation was shown to be superior to sonication, with NP fabricated from 10% PEG-PLGA having higher insulin encapsulation, lower burst release and better stability. Insulin-loaded NP maintained normoglycaemia for 24 hours in diabetic mice following a single bolus, with no evidence of hypoglycaemia.Conclusions Insulin-loaded NP prepared from 10% PEG-PLGA possessed therapeutically useful encapsulation and release kinetics when delivered by the IP route.