Key Laboratory of Advanced Technologies of Materials, Ministry of Education and School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Advanced Materials Processing and Analysis Center and Department of Materials Science and Engineering, University of Central Florida, Florida 32816, United States.
ACS Appl Mater Interfaces. 2021 May 12;13(18):21076-21086. doi: 10.1021/acsami.1c04953. Epub 2021 Apr 29.
The nontargeted distribution and uncontrolled release of drugs impede their efficacy in the treatment of rheumatoid arthritis (RA). Delivering drugs to arthritic joints and releasing drugs on demand are a feasible solution to achieve the effective treatment of RA. In this paper, we report a facile method to assemble dual-stimuli responsive polymeric micelles from polyethylene glycol-phenylboric acid-triglycerol monostearate (PEG-PBA-TGMS, PPT) conjugates with the aim of delivering dexamethasone (Dex) to arthritic joints and controlling the release of Dex by inflammatory stimuli. We show that the release of Dex from the PPT micelles is accelerated in response to acidic pH and overexpressed matrix metalloproteinases. In an adjuvant-induced arthritis model, the PPT micelles preferentially accumulate in arthritic joints and show an excellent therapeutic efficacy after being intravenously administrated. Our results highlight the potential of the dual stimuli-responsive micelles as a promising therapeutic option for the effective treatment of inflammatory diseases.
药物的非靶向分布和不受控制的释放会阻碍其在类风湿关节炎（RA）治疗中的疗效。将药物递送到关节炎关节并按需释放药物是实现 RA 有效治疗的可行解决方案。在本文中，我们报告了一种从聚乙二醇-苯硼酸-三硬脂酸甘油酯（PEG-PBA-TGMS，PPT）缀合物组装双重刺激响应性聚合物胶束的简便方法，目的是将地塞米松（Dex）递送到关节炎关节并通过炎症刺激控制 Dex 的释放。我们表明，Dex 从 PPT 胶束中的释放会响应酸性 pH 和过表达的基质金属蛋白酶而加速。在佐剂诱导的关节炎模型中，PPT 胶束优先积聚在关节炎关节中，并在静脉给药后表现出优异的治疗效果。我们的结果强调了双重刺激响应性胶束作为治疗炎症性疾病的有效治疗的有前途的治疗选择的潜力。
