Authors
Shu Pan, Nan Dong, Haoyang Yuan, Yu Zhang, Haibing He, Tian Yin, Yanjiao Wang, Jingxin Gou, Xing Tang
Published in
Expert opinion on drug delivery. Sep 22, 2025. Epub Sep 22, 2025.
Abstract
Glucagon-like peptide-1 (GLP-1) receptor agonists have demonstrated significant clinical efficacy in recent years for the treatment of type 2 diabetes mellitus (T2DM) and obesity. However, their widespread application remains constrained by limitations such as low oral bioavailability and poor patient compliance due to frequent injections. This study developed a biphasic delivery system (Ex-NPs-gel) integrating poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PLGA-PEG-PLGA) thermosensitive hydrogel with nanoparticles (NPs) for sustained-release injectable formulations.
Exenatide-loaded nanoparticles (Ex-NPs) were prepared via the double emulsion solvent evaporation method and encapsulated into PLGA-PEG-PLGA hydrogel. The prepared NPs and hydrogel composite were subsequently evaluated for their physicochemical properties and in vitro/in vivo performance.
In vitro studies demonstrated that Ex-NPs-gel achieved sustained exenatide release over 31 days with an initial burst release below 9% within the first 24 hours. In T2DM rat models, a single administration induced fasting blood glucose stabilization for over 15 days and restored hepatic/pancreatic functions.
This system overcomes technical bottlenecks of conventional PLGA carriers and single-phase gels through modulation of release kinetics, offering a biocompatible and clinically translatable solution for long-acting polypeptide delivery.
PMID:
40977331
Bibliographic data and abstract were imported from PubMed on 22 Sep 2025.
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