International Journal of Nanomedicine (Feb 2024)

Microstructure Formation and Characterization of Long-Acting Injectable Microspheres: The Gateway to Fully Controlled Drug Release Pattern

  • Wang M,
  • Wang S,
  • Zhang C,
  • Ma M,
  • Yan B,
  • Hu X,
  • Shao T,
  • Piao Y,
  • Jin L,
  • Gao J

Journal volume & issue
Vol. Volume 19
pp. 1571 – 1595

Abstract

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Mengdi Wang,1,* Shan Wang,1,* Changhao Zhang,2,* Ming Ma,1 Bohua Yan,1 Xinming Hu,2 Tianjiao Shao,2 Yan Piao,2 Lili Jin,2 Jing Gao1 1State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, People’s Republic of China; 2College of Pharmacy, Key Laboratory of Natural Medicines of the Changbai Mountain of Ministry of Education, Yanbian University, Yanji, Jilin, 133002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Gao; Lili Jin, Email [email protected]; [email protected]: Long-acting injectable microspheres have been on the market for more than three decades, but if calculated on the brand name, only 12 products have been approved by the FDA due to numerous challenges in achieving a fully controllable drug release pattern. Recently, more and more researches on the critical factors that determine the release kinetics of microspheres shifted from evaluating the typical physicochemical properties to exploring the microstructure. The microstructure of microspheres mainly includes the spatial distribution and the dispersed state of drug, PLGA and pores, which has been considered as one of the most important characteristics of microspheres, especially when comparative characterization of the microstructure (Q3) has been recommended by the FDA for the bioequivalence assessment. This review extracted the main variables affecting the microstructure formation from microsphere formulation compositions and preparation processes and highlighted the latest advances in microstructure characterization techniques. The further understanding of the microsphere microstructure has significant reference value for the development of long-acting injectable microspheres, particularly for the development of the generic microspheres. Keywords: long-acting injectable microsphere, microstructure, PLGA, controlled drug release

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