Improvement of liraglutide release from PLGA microspheres by a porous microsphere-gel composite system

Abstract

In the current work, we aimed to prepare a liraglutide-loaded porous microsphere-gel composite system. By employing polyethylene glycol (PEG) as a porogenic agent and poly (lactic-co-glycolic acid) copolymer (PLGA) as a carrier, the liraglutide microspheres were prepared and dispersed in a temperature-sensitive gel made of poloxamer 407 (F-127) and poloxamer 188 (F-68), which served as the gel matrix, to construct the composite system. The porous microsphere-gel composite system demonstrated prolonged and steady drug release, with a reduction to 4.7% in the initial release within 1 d, according to data from in vitro release tests. The drug release from the porous microspheres decreased from 53% to 29% during the rapid release phase as the PEG concentration increased and the release rate slowed down. In vivo experiments in rats revealed that the composite system prolonged the release period by about 10 d. The pharmacokinetic parameter AUC_0-1 was decreased by 24.78 ng/ml*h, the initial burst release was decreased, and the blood drug concentration fluctuation was lessened. The construction of a porous microsphere-gel composite matrix offers a novel approach to the systems with a sustained, long-lasting release that utilizes rational design.

Graphical Abstract

Keywords:

• Liraglutide
• porous microsphere
• porous microsphere-gel composite system
• initial release
• rapid release

Acknowledgements

We thank the School of Pharmacy, Yantai University, and Shandong Luye Pharmaceutical Co., Ltd. for their support and assistance in this study.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

No funding or other external support was received for this study.