Insulin Extended Release from PLA-PEG Stereocomplex Nanoparticles

Tovi Shapira-Furman, Abraham J. Domb

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


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, stereocomplexation of the peptide, insulin, is applied, onto D-PLA-PEG in aqueous media. Nanoparticles of ≈400 nm are 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 shows sustained release for 14 weeks. The therapeutic efficacy of the PLA-insulin stereocomplex nanoparticles are evaluated in diabetic Akita mice. Blood glucose levels and body weight are 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 present 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.

Original languageEnglish
JournalMacromolecular Bioscience
Early online date29 Nov 2023
StateE-pub ahead of print - 29 Nov 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.


  • controlled release
  • drug delivery
  • insulin
  • peptide drug
  • stereocomplex


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