Cytokine storm is a phenomenon whereby the overreaction of the human immune system leads to the release of inflammatory cytokines, which can lead to multiple organ dysfunction syndrome. At present, the existing drugs for the treatment of cytokine storm have limited efficacy and severe adverse effects. Here, we report a lymphatic targeting self-microemulsifying drug delivery system containing baicalein to effectively inhibit cytokine storm. Baicalein self-microemulsion with phospholipid complex as an intermediate carrier (BAPC-SME) prepared in this study could be spontaneously emulsified to form 12-nm oil-in-water nanoemulsion after administration. And then BAPC-SME underwent uptake by enterocyte through endocytosis mediated by lipid valve and clathrin, and had obvious characteristics of mesenteric lymph node targeting distribution. Oral administration of BAPC-SME could significantly inhibit the increase in plasma levels of 14 cytokines: TNF-α, IL-6, IFN-γ, MCP-1, IL-17A, IL-27, IL-1α, GM-CSF, MIG, IFN-β, IL-12, MIP-3α, IL-23, and RANTES in mice experiencing systemic cytokine storm. BAPC-SME could also significantly improve the pathological injury and inflammatory cell infiltration of lung tissue in mice experiencing local cytokine storm. This study does not only provide a new lymphatic targeted drug delivery strategy for the treatment of cytokine storm but also has great practical significance for the clinical development of baicalein self-microemulsion therapies for cytokine storm.

中文翻译：

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基于药物-磷脂复合物的黄芩素自微乳缓解细胞因子风暴

细胞因子风暴是人体免疫系统过度反应导致炎症细胞因子释放，从而导致多器官功能障碍综合征的一种现象。目前，现有治疗细胞因子风暴的药物疗效有限，不良反应严重。在这里，我们报道了一种含有黄芩素的淋巴靶向自微乳化给药系统，可有效抑制细胞因子风暴。本研究制备的以磷脂复合物为中间载体的黄芩素自微乳（BAPC-SME）给药后可自发乳化形成12nm的水包油纳米乳。然后BAPC-SME通过脂瓣和网格蛋白介导的内吞作用被肠细胞摄取，具有明显的肠系膜淋巴结靶向分布特征。口服BAPC-SME可显着抑制14种细胞因子血浆水平升高：TNF-α、IL-6、IFN-γ、MCP-1、IL-17A、IL-27、IL-1α、GM-CSF、经历全身细胞因子风暴的小鼠的 MIG、IFN-β、IL-12、MIP-3α、IL-23 和 RANTES。BAPC-SME还可以显着改善局部细胞因子风暴小鼠肺组织的病理损伤和炎症细胞浸润。本研究不仅为细胞因子风暴的治疗提供了一种新的淋巴管靶向给药策略，而且对黄芩素自微乳治疗细胞因子风暴的临床开发具有重要的现实意义。和 RANTES 在经历全身细胞因子风暴的小鼠中。BAPC-SME还可以显着改善局部细胞因子风暴小鼠肺组织的病理损伤和炎症细胞浸润。本研究不仅为细胞因子风暴的治疗提供了一种新的淋巴管靶向给药策略，而且对黄芩素自微乳治疗细胞因子风暴的临床开发具有重要的现实意义。和 RANTES 在经历全身细胞因子风暴的小鼠中。BAPC-SME还可以显着改善局部细胞因子风暴小鼠肺组织的病理损伤和炎症细胞浸润。本研究不仅为细胞因子风暴的治疗提供了一种新的淋巴管靶向给药策略，而且对黄芩素自微乳治疗细胞因子风暴的临床开发具有重要的现实意义。