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An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis

An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis

作     者:Xianyan Qin Yingying Xu Xu Zhou Tao Gong Zhi-Rong Zhang Yao Fu Xianyan Qin;Yingying Xu;Xu Zhou;Tao Gong;Zhi-Rong Zhang;Yao Fu

作者机构:Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan ProvinceSichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China Key Laboratory of Advanced Technologies of MaterialsMinistry of Education and School of Materials Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China Sichuan Provincial Orthopedic HospitalChengdu 610041China 

出 版 物:《Acta Pharmaceutica Sinica B》 (药学学报(英文版))

年 卷 期:2021年第11卷第3期

页      面:835-847页

核心收录:

学科分类:1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 100602[医学-中西医结合临床] 

基  金:supported by the National Natural Science Foundation of China (81773654, 81690261, 81503018) SichuanProvincial Science and Technology Department (2019YJ0019,China) National Key Research and Development Plan of China(2017YFC1104601) Sichuan University Fund for Excellent Young Scholars (2017SCU04A23, China) 111 Project(B18035, China)。 

主  题:Hydrogel "Plum-pudding"structure Localized therapy Controlled release Renal fibrosis Inflammation Celastrol Anti-TGFβantibody 

摘      要:Localized delivery,comparing to systemic drug administration,offers a unique alternative to enhance efficacy,lower dosage,and minimize systemic tissue toxicity by releasing therapeutics locally and specifically to the site of interests.Herein,a localized drug delivery platform (plum?puddingstructure) with controlled release and long-acting features is developed through an injectable hydrogel (pudding) crosslinked via self-assembled triblock polymeric micelles (plum) to help reduce renal interstitial fibrosis.This strategy achieves controlled and prolonged release of model therapeutics in the kidney for up to three weeks in mice.Following a single injection,local treatments containing either anti-inflammatory small molecule celastrol or anti-TGFb antibody effectively minimize inflammation while alleviating fibrosis via inhibiting NF-k B signaling pathway or neutralizing TGF-b1 locally.Importantly,the micelle-hydrogel hybrid based localized therapy shows enhanced efficacy without local or systemic toxicity,which may represent a clinically relevant delivery platform in the management of renal interstitial fibrosis.

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