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AAPS PharmSciTech. 2019 Jan 9;20(2):64. doi: 10.1208/s12249-018-1208-8.

Formation Mechanism, In vitro and In vivo Evaluation of Dimpled Exenatide Loaded PLGA Microparticles Prepared by Ultra-Fine Particle Processing System.

Author information

1
Guangdong University of Technology, Institute for Biomedical and Pharmaceutical Sciences, Guangzhou, 510006, China.
2
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
3
Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
4
Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China.
5
Guangdong University of Technology, Institute for Biomedical and Pharmaceutical Sciences, Guangzhou, 510006, China. went@gdut.edu.cn.
6
Guangdong University of Technology, Institute for Biomedical and Pharmaceutical Sciences, Guangzhou, 510006, China. wuchuanb@mail.sysu.edu.cn.
7
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China. wuchuanb@mail.sysu.edu.cn.

Abstract

Spherical poly (D, L-lactic-co-glycolic acid) microparticles (PLGA-MPs) have long been investigated in order to achieve sustained delivery of proteins/peptides. However, the formation mechanism and release characteristics of the specific shape MPs were still unknown. This study aimed to develop a novel-dimpled exenatide-loaded PLGA-MPs (Exe-PLGA-MPs) using an ultra-fine particle processing system (UPPS) and investigate the formation mechanism and release characteristics. Exe-PLGA-MPs were prepared by UPPS and optimized based on their initial burst within the first 24 h and drug release profiles. Physicochemical properties of Exe-PLGA-MPs, including morphology, particle size, and structural integrity of Exe extracted from Exe-PLGA-MPs, were evaluated. Furthermore, pharmacokinetic studies of the optimal formulation were conducted in Sprague-Dawley (SD) rats to establish in vitro-in vivo correlations (IVIVC) of drug release. Exe-PLGA-MPs with dimpled shapes and uniform particle sizes achieved a high encapsulation efficiency (EE%, 91.50 ± 2.65%) and sustained drug release for 2 months in vitro with reduced initial burst (20.42 ± 1.64%). Moreover, the pharmacokinetic studies revealed that effective drug concentration could be maintained for 3 weeks following a single injection of dimpled Exe-PLGA-MPs with high IVIVC. Dimpled PLGA-MPs prepared using the UPPS technique could thus have great potential for sustained delivery of macromolecular proteins/peptides.

KEYWORDS:

dimpled; drug release; exenatide; pharmacokinetics; ultra-fine particle processing system (UPPS)

PMID:
30627822
DOI:
10.1208/s12249-018-1208-8

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