Original articles
Xianyan Qin, Yingying Xu, Xu Zhou, Tao Gong, Zhi-Rong Zhang, Yao Fu. An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis[J]. Acta Pharmaceutica Sinica B, 2021, 11(3): 835-847

An injectable micelle-hydrogel hybrid for localized and prolonged drug delivery in the management of renal fibrosis
Xianyan Qina,b, Yingying Xua, Xu Zhoua,c, Tao Gonga, Zhi-Rong Zhanga, Yao Fua
a 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;
b Key Laboratory of Advanced Technologies of Materials, Ministry of Education and School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China;
c Sichuan Provincial Orthopedic Hospital, Chengdu 610041, China
Abstract:
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.
Key words:    Hydrogel    “Plum-pudding&rdquo    structure    Localized therapy    Controlled release    Renal fibrosis    Inflammation    Celastrol    Anti-TGFβ antibody   
Received: 2020-06-23     Revised: 2020-09-04
DOI: 10.1016/j.apsb.2020.10.016
Funds: This work was supported by the National Natural Science Foundation of China (81773654, 81690261, 81503018), Sichuan Provincial Science and Technology Department (2019YJ0019, China), National Key Research and Development Plan of China (2017YFC1104601), Sichuan University Fund for Excellent Young Scholars (2017SCU04A23, China), and 111 Project (B18035, China).
Corresponding author: Yao Fu     Email:yfu4@scu.edu.cn
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Xianyan Qin
Yingying Xu
Xu Zhou
Tao Gong
Zhi-Rong Zhang
Yao Fu

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