Basic Study
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World J Diabetes. Aug 15, 2022; 13(8): 613-621
Published online Aug 15, 2022. doi: 10.4239/wjd.v13.i8.613
Improved systemic half-life of glucagon-like peptide-1-loaded carbonate apatite nanoparticles in rats
Nabilah Ibnat, Rahela Zaman, Mohammad Borhan Uddin, Ezharul Chowdhury, Chooi Yeng Lee
Nabilah Ibnat, Rahela Zaman, Mohammad Borhan Uddin, Ezharul Chowdhury, School of Medicine and Health Sciences, Monash University Malaysia, Subang Jaya 47500, Selangor, Malaysia
Chooi Yeng Lee, School of Pharmacy, Monash University Malaysia, Subang Jaya 47500, Selangor, Malaysia
Author contributions: Lee CY and Chowdhury E contributed to the study concept and design; Ibnat N, Zaman R and Uddin B acquired the data; Ibnat N, Uddin B, Lee CY and Chowdhury E analysed the data; Ibnat N drafted the manuscript; Lee CY reviewed and edited the manuscript; all authors have read and approved the final manuscript.
Supported by an FRGS grant from the Ministry of Education, Malaysia, No. FRGS/2/2014/SG05/MUSM/03/1.
Institutional animal care and use committee statement: The study was reviewed and approved by the Monash University Animal Ethics Committee (Approval No. MARP/2016/008).
Conflict-of-interest statement: There is no conflict-of-interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chooi Yeng Lee, PhD, Senior Lecturer, School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Subang Jaya 47500, Selangor, Malaysia. chooi.yeng.lee@monash.edu
Received: December 15, 2021
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
Processing time: 240 Days and 10.9 Hours
Abstract
BACKGROUND

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.

AIM

To prepare GLP1-encapsulated nanosize particle with controlled release property to improve the systemic half-life of GLP1.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Keywords: Glucagon-like peptide-1; Metabolic syndrome; Nanoparticles; Plasma half-life; Rat

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.