Published online Aug 15, 2022. doi: 10.4239/wjd.v13.i8.613
Peer-review started: December 15, 2021
First decision: January 12, 2022
Revised: January 24, 2022
Accepted: July 16, 2022
Article in press: July 16, 2022
Published online: August 15, 2022
Glucagon-like peptide-1 (GLP1) is an endogenous peptide that regulates blood glucose level. But its susceptibility to rapid metabolic degradation limits its therapeutic use.
To prepare GLP1-encapsulated nanosize particle with controlled release property to improve the systemic half-life of GLP1.
GLP1 nanoparticles were prepared by complexation of GLP1 with carbonate apatite nanoparticles (CA NPs). The physicochemical properties of the CA NPs, the effects of GLP1-loaded CA NPs on cell viability, and the systemic bioavailability of GLP1 after CA NPs administration were determined.
The GLP1-loaded CA NPs was within 200 nm in size and stable in fetal bovine serum. The formulation did not affect the viability of human cell lines suggesting that the accumulation of CA NPs in target tissues is safe. In Sprague Dawley rats, the plasma GLP1 Levels as measured from the GLP1-loaded CA NPs-treated rats, were significantly higher than that of the control rats and free GLP1-treated rats at 1 h post-treatment (P < 0.05), and the level remained higher than the other two groups for at least 4 h.
The GLP1-loaded CA NPs improved the plasma half-life of GLP1. The systemic bioavailability of GLP1 is longer than other GLP1 nanoparticles reported to date.
Core Tip: Glucagon-like peptide-1 (GLP1), owing to its physiological properties, is a promising peptide in the treatment of obesity and diabetes. Due to the short half-life of GLP1 and in order to improve GLP1 therapeutic use, GLP1 receptor agonists (GLP1-RAs) have been widely synthesised and encapsulated into nanocarriers for targeted delivery. But the use of GLP1-RAs is associated with unwanted side effects and risks. In the present study, we synthesised a new nanocarrier for native GLP1 - the GLP1 carbonate apatite nanoparticles. The nanocarrier appears comparable if not significantly better than other GLP1 nanoparticles, which have shown promising features as therapeutic agents.