Preparation of enzyme based polymeric biomimetic nanoparticle for the controlled release of insulin

Abstract

This study aims to assess the faster responsiveness of the insulin release which is a self-regulated insulin delivery system constructed by encapsulating insulin and enzyme glucose oxidase into hyaluronic acid and 2-nitroimidazole which works mainly for stabilizing the hyperglycemia state based on the blood glucose level. Enzyme based nanoparticles were prepared by simple ionic gelation method. Insulin loaded nanoparticles kept for stability studies estimated by using human insulin enzyme linked immunosorbent assay (ELISA Kit) showing stability upto 30 days at 4 °C. The average diameter of the nanoparticles were having around 193 nm and achieved high insulin entrapment efficiencies (approximately 85%). In vitro studies showed the release of insulin from enzyme based nanoparticles which was effectively correlated by creating an external blood glucose different glycemic environment where different concentrations of glucose were taken estimated by human insulin ELISA assay. The equilibrium was achieved for high glucose concentration at 400 mg/dL (hyperglycemia state) was cumulative increase upto 53% of insulin release with immediate stabilization observed within 0.5 h and glucose concentration (moderate hyperglycemia) at 250 mg/dL showed release of insulin upto 43.5% with stable decline. Normal glucose level at 100 mg/dL (normoglycemia) showed normal release upto 25.3% whereas with less glucose concentration at 50 mg/dL (hypoglycemia state) only 15% release was found. Overall, this preliminary study showed excellent rapid responsiveness towards hyperglycemia condition which might act as a potential biomimetic system in triggering the release of insulin in sustained manner. Keywords: Drug delivery, Glucose oxidase, Hyperglycemia, Nanoparticle, Insulin