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.

与全身性药物给药相比，局部递送可提供独特的替代方法，以通过局部释放治疗药物（特别是向目标部位释放）来提高疗效，降低剂量并最大程度地降低全身组织毒性。本文中，通过可注射水凝胶（“布丁”）通过自组装三嵌段聚合物胶束（“李子”）交联开发了具有控释和长效功能的局部药物输送平台（“李子布丁”结构），以帮助减少肾间质纤维化。此策略可在小鼠中实现模型治疗剂在肾脏中受控和延长释放长达三周的时间。在单次注射，含有局部治疗或者抗炎小分子雷公藤红素或抗TGF β抗体有效减少炎症同时缓解纤维化通过抑制NF- κ乙信号传导途径或中和TGF- β 1本地。重要的是，基于胶束-水凝胶杂化的局部疗法显示出增强的功效而没有局部或全身毒性，这可能代表了在肾间质纤维化的治疗中临床上相关的递送平台。