Preparation, Characterization and Hypoglycaemic Effects of Orally Delivered Insulin-Loaded PLGA Nanoparticles in Diabetic Rats

摘要

To date, invasive methods are still the main routes for insulin administration, and are painful and costly. Oral insulin pills are not available because of the quick degradation of insulin in the gastrointestinal (GI) tract. In this study, we developed insulin-loaded poly(lactic-co-glycolic acid) nanoparticles (insulin-PLGA-NPs) that could prevent insulin degradation, keep the biological activity of insulin and effectively reduce blood glucose levels in diabetic rats. Under optimized conditions, the insulin-PLGA-NPs were spherical (diameter = 195.6 +/- 11.36 nm) and smooth, with high encapsulation efficiency (EE) (91.3 +/- 2.4%) and stability. Oral administration of insulin-PLGA-NPs to diabetic rats was found to have a r hypoglycaemic effect similar to that of an insulin subcutaneous (SC) single injection, with a much longer effective period. In addition, oral administration of FITC-insulin-loaded PLGA nanoparticles (FITC-PLGA-NPs) revealed that most of them were absorbed by the stomach and small intestine. Finally, using histopathological analysis, no adverse effects were observed in the tested organs of the diabetic rats after oral administration. These results showed that the prepared oral insulin-PLGA-NPs would be an effective and safe alternative to the current insulin injections and provide valuable information for further non-invasive insulin development.