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...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-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.展开更多
基金supported by the National Natural Science Foundation of China (81773654, 81690261, 81503018)SichuanProvincial Science and Technology Department (2019YJ0019,China)+2 种基金National Key Research and Development Plan of China(2017YFC1104601)Sichuan University Fund for Excellent Young Scholars (2017SCU04A23, China)111 Project(B18035, China)。
文摘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-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.
文摘【目的】探讨补肾活血化痰法改善自发性高血压大鼠(SHR)左心室纤维化机制。【方法】选用20只自发性高血压大鼠,随机分为模型组和中药组,10只WKY大鼠(Wistar-Kyoto rat)作为正常对照组。干预12周后,应用Masson染色法检测大鼠左心室纤维化程度,逆转录—聚合酶链反应(RT-PCR)法检测大鼠左心室Smad3 m RNA表达水平,Western blot法检测大鼠左心室Smad3表达水平。【结果】中药组大鼠心肌纤维化水平、Smad3蛋白表达水平、Smad3基因表达水平显著低于模型组(均P<0.05)。【结论】补肾活血化痰法可能通过抑制Smad3表达改善自发性高血压大鼠左心室纤维化进程。
