New Injectable Gel Delivers Exenatide Slowly for Long-Lasting Blood Sugar Control | Research

The takeaway

A dual-phase delivery system combining nanoparticles with a temperature-sensitive hydrogel provided sustained exenatide release and prolonged blood sugar control in diabetic rats.

Dual-phase release
Nanoparticle-hydrogel system provides rapid initial then sustained exenatide delivery from a single injection

What the researchers found

The biphasic delivery system (Ex-NPs-gel) provided both rapid initial and sustained long-term exenatide release, achieving prolonged glycemic control compared to standard exenatide injections in diabetic rats.

Why it matters

Poor patient compliance due to frequent injections is a major barrier for GLP-1 agonist therapy. A single injection that provides weeks of drug release could dramatically improve treatment adherence and outcomes for millions of diabetes patients.

The numbers in context

- Sustained release over 31 days in vitro

- Initial burst release below 9% in first 24 hours

- Single injection stabilized blood glucose for 15+ days in diabetic rats

- Restored hepatic and pancreatic functions

How the study worked

Animal study developing and testing PLGA nanoparticles loaded with exenatide, embedded in PLGA-PEG-PLGA thermosensitive hydrogel. Characterized particle properties and release kinetics, then tested in vivo glycemic control in diabetic rat models.

Who was studied

In vitro release studies and type 2 diabetic rat models. PLGA-PEG-PLGA thermosensitive hydrogel with exenatide-loaded PLGA nanoparticles.

What this study cannot tell us

Animal study only — rat pharmacokinetics differ from human; long-term biocompatibility of implanted hydrogel needs assessment; manufacturing scalability and cost not addressed; comparison with existing long-acting formulations (weekly semaglutide) not performed.

How to read the evidence

Preclinical proof-of-concept in animal models. Demonstrates technical feasibility but requires extensive further development for clinical use.

When this study was published

Published in 2025, reflecting ongoing innovation in peptide drug delivery systems.

The bigger picture

This delivery approach could be applied to many peptide drugs that currently require frequent injections. If successful in humans, it could transform how GLP-1 agonists and other peptide therapeutics are administered, making treatment more convenient and effective.

Questions still open

How long does a single injection provide therapeutic exenatide levels compared to weekly injectable formulations?
Is the hydrogel fully biodegradable, and does it cause any local tissue reaction?
Could this delivery platform be adapted for other peptide drugs like semaglutide or liraglutide?

Common questions

How does a thermosensitive hydrogel work?

The gel is liquid at room temperature, making it easy to inject. Once inside the body at 37°C, it solidifies into a gel depot that slowly releases the drug over time. Think of it as a tiny drug reservoir that forms automatically under the skin.

Why can't people just take exenatide as a pill?

Like most peptide drugs, exenatide is a small protein that would be destroyed by stomach acid and digestive enzymes if swallowed. That's why it needs to be injected, and why researchers are developing sustained-release systems to reduce how often injections are needed.

Read the original research

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

Expert opinion on drug delivery, 22(12), 2001-2015

View on PubMed ↗Publisher’s paper ↗

Citation

Pan, Shu; Dong, Nan; Yuan, Haoyang; Zhang, Yu; He, Haibing; Yin, Tian; Wang, Yanjiao; Gou, Jingxin; Tang, Xing. (2025). Dual-phase exenatide delivery system: PLGA nanoparticles embedded in thermosensitive PLGA-PEG-PLGA hydrogel for sustained glycemic control.. Expert opinion on drug delivery, 22(12), 2001-2015. https://doi.org/10.1080/17425247.2025.2564870