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

Acta Pharmaceutica Sinica B 2021年第3期11卷 835-847页

作者： Xianyan Qin Yingying Xu Xu Zhou Tao Gong Zhi-Rong Zhang Yao Fu Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan 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 Materials Ministry of Education and School of Materials Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China Sichuan Provincial Orthopedic Hospital Chengdu 610041China

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 ***,a localized drug delivery platform ("plum?pudding"structure) 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 *** strategy achieves controlled and prolonged release of model therapeutics in the kidney for up to three weeks in *** 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 ***,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.

关键词： Hydrogel "plum-pudding"structure Localized therapy Controlled release Renal fibrosis Inflammation Celastrol Anti-TGFβantibody

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