AAPS PharmSciTech

, 20:64 | Cite as

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

  • Chune Zhu
  • Tingting Peng
  • Di Huang
  • Disang Feng
  • Xinyi Wang
  • Xin Pan
  • Wen TanEmail author
  • Chuanbin WuEmail author
Research Article


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.


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





dimethyl carbonate


drug loading


encapsulation efficiency


exenatide loaded PLGA-MPs


glucagon-like peptide-1


in vitro-in vivo correlations




mean residence time


D, L-lactic-co-glycolic acid


relative bioavailability




sodium dodecyl sulfate-polyacrylamide gel electrophoresis


synchrotron radiation X-ray computed microtomography


solid in oil in water


ultra-fine particle processing system


water in oil


water in oil in oil


water in oil in water


Funding Information

This work was funded by the China Postdoctoral Science Foundation (Grant No. 2016M602442), the Natural Science Fund Project of Guangdong Province (Grant No. 2018A030310555, 2016A030312013).

Compliance with Ethical Standards

This study was approved by the Ethical Committee on Animal Experimentation at Sun Yat-sen University.

Conflict of Interest

The authors declare that there is no conflict of interest.

Supplementary material

12249_2018_1208_MOESM1_ESM.docx (1.5 mb)
ESM 1 (DOCX 1546 kb)


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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  1. 1.Guangdong University of TechnologyInstitute for Biomedical and Pharmaceutical SciencesGuangzhouChina
  2. 2.School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhouChina
  3. 3.Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
  4. 4.Guanghua School of Stomatology, Hospital of StomatologySun Yat-sen UniversityGuangzhouChina

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