Peng He,1,* Jing Sun,1,* Jian Tan,1,* Ya-Ning Shi,1,2 Chan-Juan Zhang,1 Neng Zhu,3 Qiong Yang,1 Li Qin1,4 

1Laboratory of Stem Cell Regulation and Application of Traditional Chinese Medicine, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China; 2Science and Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China; 3The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410007, People’s Republic of China; 4Hunan Key Laboratory of Vascular Biology and Translational Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Li Qin, Email Lqin@hnucm.edu.cn

Abstract: Celastrol (CeT) is the first pentacyclic triterpenoid compound isolated from the root bark of Tripterygium wilfordii. It has a broad spectrum of pharmacological activities, including anti-fibrosis, anti-tumor, anti-inflammation, immunomodulation, antioxidation, and neuroprotective effects. Despite the considerable therapeutic potential, the clinical application of CeT has been severely hindered by several inherent limitations, including poor aqueous solubility and permeability, low oral bioavailability, short plasma half-life, cytotoxicity, organ toxicity and so on. In recent years, the rapid development of nanotechnology has provided innovative strategies to address these challenges. The targeted drug delivery system based on nanomaterials can improve the administration defects of CeT and enhance its therapeutic efficacy. This review systematically summarizes the challenges faced by CeT in the drug delivery process, and discusses the latest progress of nanodelivery strategies in overcoming these challenges from both active and passive targeting aspects, including the application of nanosystems such as polymer micelles, liposomes, nanoparticles and nanogels, and other nanosystems, providing references for the further development and clinical application of CeT.

Keywords: celastrol, structural defects, traditional chinese medicine, drug delivery systems, targeted delivery, nanomedicine