Nanomedicine-based combination of dexamethasone palmitate and MCL-1 siRNA for synergistic therapeutic efficacy against rheumatoid arthritis,Drug Delivery and Translational Research

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Nanomedicine-based combination of dexamethasone palmitate and MCL-1 siRNA for synergistic therapeutic efficacy against rheumatoid arthritis
Drug Delivery and Translational Research ( IF 5.7 ) Pub Date : 2021-07-30 , DOI: 10.1007/s13346-021-01037-x
Yanmei Li ₁ , Shitong Wei ₁ , Yonghua Sun ₁ , Shihua Zong ₁ , Yameng Sui ₁

Affiliation

The main aim of this research was to design a MCL-1 siRNA and dexamethasone (DEX)-loaded folate modified poly(lactide-co-glycolide) (PLGA)-based polymeric micelles with an eventual goal to improve the therapeutic outcome in the rheumatoid arthritis (RA). Polymeric micelles encapsulating the MCL-1 siRNA and DEX was successfully developed and observed to be stable. Physicochemical characteristics such as particle size and particle morphology were ideal for the systemic administration. Folate-conjugated DEX/siRNA-loaded polymeric micelles (DS-FPM) significantly lowered the MCL-1 mRNA expression compared to either DEX/siRNA-loaded polymeric micelles (DS-PM) or free siRNA in Raw264.7 cells and macrophage cells suggesting the importance of targeted nanocarriers. Most importantly, DS-FPM exhibited a greatest decrease in the hind paw volume with lowest clinical score compared to any other treated group indicating a superior anti-inflammatory activity. DS-FPM showed significantly lower levels of the TNF-α and IL-1β compared to AIA model and free groups. The folate receptor (FR)-targeting property of DS-FPM has been demonstrated to be a promising delivery platform for the effective delivery of combination therapeutics (siRNA and DEX) toward the treatment of rheumatoid arthritis.

Graphical abstract

中文翻译：

基于纳米药物的地塞米松棕榈酸酯和 MCL-1 siRNA 的组合对类风湿性关节炎具有协同治疗功效

本研究的主要目的是设计一种 MCL-1 siRNA 和负载地塞米松 (DEX) 的叶酸修饰聚丙交酯乙交酯 (PLGA) 基聚合物胶束，最终目标是改善类风湿的治疗效果关节炎（RA）。成功开发了封装 MCL-1 siRNA 和 DEX 的聚合物胶束，并观察到其稳定。粒径和颗粒形态等理化特性对于全身给药来说是理想的。在 Raw264.7 细胞和巨噬细胞中，与负载 DEX/siRNA 的聚合物胶束 (DS-PM) 或游离 siRNA 相比，叶酸缀合的 DEX/siRNA 负载的聚合物胶束 (DS-FPM) 显着降低了 MCL-1 mRNA 表达，表明靶向纳米载体的重要性。最重要的是，与任何其他治疗组相比，DS-FPM 的后爪体积减少幅度最大，临床评分最低，表明具有优异的抗炎活性。与AIA模型组和自由组相比，DS-FPM显示TNF-α和IL-1β水平显着降低。 DS-FPM 的叶酸受体 (FR) 靶向特性已被证明是一种有前景的递送平台，可有效递送组合疗法（siRNA 和 DEX）来治疗类风湿性关节炎。

图文摘要

更新日期：2021-07-30

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