Journal
ACTA PHARMACEUTICA SINICA B
Volume 11, Issue 3, Pages 835-847Publisher
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2020.10.016
Keywords
Hydrogel; Plum-pudding structure; Localized therapy; Controlled release; Renal fibrosis; Inflammation; Celastrol; Anti-TGF beta antibody
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Funding
- National Natural Science Foundation of China [81773654, 81690261, 81503018]
- Sichuan Provincial Science and Technology Department, China [2019YJ0019]
- National Key Research and Development Plan of China [2017YFC1104601]
- Sichuan University Fund for Excellent Young Scholars, China [2017SCU04A23]
- 111 Project, China [B18035]
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Localized delivery offers a unique alternative to enhance efficacy and lower dosage by releasing therapeutics specifically to the site of interests, the drug delivery platform developed in this study achieves controlled and prolonged release of therapeutics in the kidney, and shows enhanced efficacy without local or systemic toxicity for the treatment of renal interstitial fibrosis.
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-TGF beta antibody effectively minimize inflammation while alleviating fibrosis via inhibiting NF-kappa B signaling pathway or neutralizing TGF-beta 1 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. (C) 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
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