Mitogen-activated protein kinases (MAPKs), including c-Jun N-terminal kinase (JNK), play important role in the regulation of pro-inflammatory cytokine secretion and signaling cascades. Therefore, JNKs are key targets for the treatment of cytokine/JNK-driven diseases. Herein, we developed electrospray poly(lactic-co-glycolic acid) (PLGA) microparticles doped with novel JNK inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime (IQ-1). Optimized electrospray parameters allowed us to produce IQ-1-doped microparticles with round shape, smooth and non-porous surface, and mean diameter of 0.9-1.3 μm. We have shown that IQ-1 was well integrated into the polymer matrix and had a prolonged release in two steps via non-Fickian release. The fabricated particles doped with IQ-1 exhibited anti-inflammatory effects, as indicated by inhibited neutrophil activation and cytokine secretion by human monocytic MonoMac-6 cells. Overall, our study demonstrates that PLGA microparticles doped with a novel JNK inhibitor (IQ-1) could be a promising delivery system for treatment of JNK-mediated diseases.

中文翻译：

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电喷雾聚（乳酸 - 共 - 乙醇酸）颗粒作为新型 JNK 抑制剂 IQ-1 的有前途的药物递送系统

丝裂原活化蛋白激酶 (MAPK)，包括 c-Jun N 末端激酶 (JNK)，在调节促炎细胞因子分泌和信号级联反应中起重要作用。因此，JNKs 是治疗细胞因子/JNK 驱动疾病的关键靶点。在此，我们开发了掺杂新型 JNK 抑制剂 11H-茚并 [1,2-b] 喹喔啉-11-酮肟 (IQ-1) 的电喷雾聚（乳酸-乙醇酸共聚物）（PLGA）微粒。优化的电喷雾参数使我们能够生产圆形、光滑无孔表面、平均直径为 0.9-1.3 μm 的 IQ-1 掺杂微粒。我们已经证明 IQ-1 很好地整合到聚合物基质中，并通过非 Fickian 释放分两步延长释放。掺杂 IQ-1 的制备的颗粒表现出抗炎作用，正如人单核细胞 MonoMac-6 细胞抑制中性粒细胞活化和细胞因子分泌所表明的那样。总体而言，我们的研究表明，掺杂新型 JNK 抑制剂 (IQ-1) 的 PLGA 微粒可能是治疗 JNK 介导的疾病的有前途的递送系统。