To the best of our knowledge, no studies have yet examined the electrostatic interaction of polyelectrolytes with electrolyte drugs for the treatment of rheumatoid arthritis (RA). Here, an injectable, electrostatically interacting drug depot is described. We prepared methoxy polyethylene glycol-b-(poly(ε-caprolactone)-ran-poly(l-lactic acid) (MC) diblock copolymers with a carboxylic acid group (MC-C) at the pendant position. MC-C was polyelectrolytes that exhibited negative zeta potentials. Sulfasalazine [Sul(−)] and minocycline [Min(+)], electrolyte RA drugs, exhibited negative and positive zeta potentials, respectively. The electrolyte RA drugs were loaded into the polyelectrolyte MC-C solution to prepare injectable, electrostatically interacting depot formulations. The formulation with an attractive electrostatic interaction [Min(+)-MC-C] exhibited gradual release of Min(+) from the MC-C depot over an extended period and suppressed the growth of inflammatory RAW 264.7 cells without affecting synovial cells. Mature chondrocytes were observed after H&E and safranin O staining of the cartilage of Min(+)-MC-C intra-articularly injected RA-induced rats. In comparison with other formulations, Min(+)-MC-C induced the suppression of the expression of pro-inflammatory proteins TNF-α and IL-1β in the articular knee joint, which resulted in the amelioration of RA. In conclusion, an injectable, electrostatically interacting depot formulation administered through intra-articular injection successfully provided almost complete amelioration of RA.

中文翻译：

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用于治疗类风湿关节炎的可注射，静电相互作用的药物仓库

据我们所知，尚无研究检查聚电解质与电解质药物在类风湿关节炎（RA）中的静电相互作用。在此，描述了一种可注射的，静电相互作用的药物仓库。我们制备的甲氧基聚乙二醇- b - （聚（ε -己内酯） -然-聚（升在侧位具有羧酸基团（MC-C）的-（乳酸）（MC）二嵌段共聚物。MC-C是表现出负ζ电势的聚电解质。电解质RA药物柳氮磺吡啶[Sul（-）]和米诺环素[Min（+）]分别显示出负的和正的zeta电位。将电解质RA药物加载到聚电解质MC-C溶液中，以制备可注射的，静电相互作用的长效制剂。具有有吸引力的静电相互作用[Min（+）-MC-C]的制剂在较长的时间内显示出从MC-C库逐渐释放的Min（+），并抑制了炎性RAW 264.7细胞的生长，而没有影响滑膜细胞。H（E）和番红素O对Min（+）-MC-C关节内注射的RA诱导的大鼠的软骨进行染色后，观察到成熟的软骨细胞。与其他制剂相比，Min（+）-MC-C抑制了膝关节中促炎蛋白TNF-α和IL-1β的表达，从而改善了RA。总之，通过关节内注射给药的可注射的，静电相互作用的长效制剂成功地提供了RA的几乎完全缓解。