A supramolecular nanoprodrug for prevention of gallstone formation  

作　　者：Xiangjun Zhang Xiaodi Yang Yan Wang Zhongping Xu Sisi Yi Tao Guo Yue Liao Xiyu Tang Jianxiang Zhang Ruibing Wang 

机构地区：[1]College of Pharmacy,Chongqing Medical University,Chongqing 400016,China [2]Chongqing University Fuling Hospital,Chongqing 408000,China [3]Department of Pharmaceutics,College of Pharmacy,Third Military Medical University(Army Medical University),Chongqing 400038,China [4]Yu-Yue Pathology Scientific Research Center,Chongqing 400039,China [5]State Key Laboratory of Trauma and Chemical Poisoning,Third Military Medical University(Army Medical University),Chongqing 400038,China [6]State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macao,Taipa,Macao 999078,China

出　　处：《Chinese Chemical Letters》2025年第2期326-331,共6页中国化学快报(英文版)

基　　金：financially supported by the National Natural Science Foundation of China(Nos.82102195,22071275 and 22271323);Natural Science Foundation of Chongqing,China(No.CSTB2022NSCQ-MSX1073);Scientific and Technological Research Program of Chongqing Municipal Education Commission(No.KJQN202100454)。

摘　　要：Cholelithiasis affects approximately 10%-20%of the adult population globally.And cholesterol accumulation and nucleation of cholesterol crystals are commonly recognized as the primary process in the initiation and progression of gallstones.Hydroxypropyl-β-cyclodextrin(HPCD)is a supramolecular host compound that can solubilize cholesterol,potentially serving as a preventative or therapeutic agent for cholelithiasis.However,we found that the administration of HPCD treatment did not impede the formation of gallstones in mice,mainly attributed to the pre-complexation of its cavity during the transition process.Here we synthesized a prodrug of HPCD and prepared a HPCD nanoparticle(HPCD-NP),which can be transported efficiently to the gallbladder through the hepatobiliary system following an intravenous injection.In the bile,the HPCD-NP degraded into free HPCD,bound to cholesterol crystals and gallstones within the gallbladder and effectively increased cholesterol solubilization,leading to gallstones regression.Given the established safety of both HPCD and cyclodextrin-based nanoparticles in numerous animal and human studies,HPCD-NP shows considerable promise for the prevention and treatment of human cholelithiasis.

关 键 词：GALLSTONE HYDROXYPROPYL-Β-CYCLODEXTRIN Hepatobiliary transport Host-guest interaction SOLUBILIZATION 

分 类 号：R575.62[医药卫生—消化系统] TB383.1[医药卫生—内科学] O641.3[医药卫生—临床医学]