Dual-phase exenatide delivery system: PLGA nanoparticles embedded in thermosensitive PLGA-PEG-PLGA hydrogel for...

Area of Science:

• Biomedical Engineering
• Drug Delivery Systems
• Pharmacology

Background:

• Glucagon-like peptide-1 (GLP-1) receptor agonists are effective for type 2 diabetes mellitus (T2DM) and obesity.
• Limitations include low oral bioavailability and frequent injections, hindering patient compliance.
• A novel biphasic delivery system was developed to address these challenges.

Purpose of the Study:

• To develop and evaluate a biphasic delivery system (Ex-NPs-gel) for sustained release of exenatide.
• To improve therapeutic outcomes for T2DM and obesity through enhanced drug delivery.

Main Methods:

• Exenatide-loaded nanoparticles (Ex-NPs) were prepared using double emulsion solvent evaporation.
• Ex-NPs were encapsulated into a poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PLGA-PEG-PLGA) thermosensitive hydrogel.
• Physicochemical properties and in vitro/in vivo performance were assessed.

Main Results:

• The Ex-NPs-gel system demonstrated sustained exenatide release over 31 days with minimal initial burst release (<9% in 24h).
• A single administration in T2DM rat models stabilized fasting blood glucose for over 15 days.
• The formulation restored hepatic and pancreatic functions in the animal model.

Conclusions:

• The biphasic delivery system overcomes limitations of conventional PLGA carriers and single-phase gels.
• This system modulates release kinetics for effective long-acting polypeptide delivery.
• The Ex-NPs-gel formulation presents a biocompatible and clinically translatable solution for T2DM and obesity management.