Insulin Extended Release from PLA-PEG Stereocomplex Nanoparticles.

This report addresses the challenges of controlled drug delivery for peptide and protein therapeutics by introducing a novel approach of nano formulation fabricated in aqueous media applying stereo-interaction mechanism with poly(D-lactide)-polyethylene glycol (D-PLA-PEG). To overcome the inherent poor stability of peptide and protein therapeutics, we applied stereocomplexation of the peptide, insulin, onto D-PLA-PEG in aqueous media. Nanoparticles of about 400 nm were spontaneously formed when water-soluble D configured PLA-PEG diblock copolymer and L- configured insulin interlock into a stereocomplex, owing to their concave convex fitness. In vitro release of insulin from stereocomplex in phosphate buffer solution (PBS) pH 7.4 solution showed sustained release for 14 weeks. The therapeutic efficacy of the PLA-insulin stereocomplex nanoparticles were evaluated in diabetic Akita mice. Blood glucose levels and body weight were closely monitored for a period of 17 weeks, revealing a significant reduction in glucose levels of the Akita mice treated with insulin stereocomplex, as well as normal body weight gain. These findings suggest that the stereocomplex nanoparticles of insulin-D-PLA-PEG presents a promising and effective sustained and extended release platform for insulin. Notably, the use of water-soluble D-PLA-PEG for stereocomplexation in water expands the applicability of this approach to fabricate controlled delivery systems for peptide and protein therapeutics. This article is protected by copyright. All rights reserved.