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

Acta Pharmaceutica Sinica B

Yingying Xu¹  Zhi-Rong Zhang²  Tao Gong³  Xu Zhou³  Yao Fu³  Xianyan Qin³ 

[1] Key Laboratory of Advanced Technologies of Materials, Ministry of Education and School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China;Sichuan Provincial Orthopedic Hospital, Chengdu 610041, China;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 Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China;

关键词: Hydrogel;    “Plum‒pudding” structure;    Localized therapy;    Controlled release;    Renal fibrosis;    Inflammation;   

DOI  :  

来源: DOAJ

【 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‒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 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-TGFβ antibody effectively minimize inflammation while alleviating fibrosis via inhibiting NF-κB signaling pathway or neutralizing TGF-β1 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.

【 授权许可】

Unknown