The protective effects of histone deacetylase (HDAC) inhibitors were highlighted in the treatment of kidney diseases, especially acute kidney injury (AKI). However, the currently available HDAC inhibitor cannot be delivered to the kidney properly because of its poor solubility in aqueous solutions. Therefore, calcium alginate (Ca-ALG) microspheres were proposed as microcarriers for the delivery of HDAC inhibitors in this study. First, Ca-ALG microspheres with high sphericity were obtained by a single-emulsion microfluidic strategy. Then, we selected suitable Ca-ALG microspheres for HDAC inhibitor loading by analyzing the swelling ratio and the release property using different parameters. Besides, thermal stimulation will change the drug release property of Ca-ALG microspheres in in vitro experiments. Furthermore, the HDAC inhibitor-loaded microspheres were delivered to the kidney by renal subcapsular injection for evaluating the treatment effects in mice with ischemia-reperfusion-induced AKI. The in vivo results showed that the HDAC inhibitor-loaded Ca-ALG microspheres could effectively reduce the renal regional inflammatory response and macrophage infiltration. Taken together, we proposed a promising therapy with an effective kidney-targeted drug delivery for the treatment of AKI.

中文翻译：

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组蛋白去乙酰化酶抑制剂负载海藻酸钙微球治疗急性肾损伤

组蛋白去乙酰化酶 (HDAC) 抑制剂的保护作用在肾脏疾病，尤其是急性肾损伤 (AKI) 的治疗中得到了强调。然而，目前可用的 HDAC 抑制剂由于其在水溶液中的溶解度差，无法正确输送至肾脏。因此，本研究提出海藻酸钙 (Ca-ALG) 微球作为微载体用于递送 HDAC 抑制剂。首先，通过单乳液微流体策略获得了具有高球形度的Ca-ALG微球。然后，我们通过使用不同参数分析溶胀率和释放特性，选择合适的 Ca-ALG 微球用于 HDAC 抑制剂的负载。此外，热刺激会改变Ca-ALG微球的体外释药特性。实验。此外，通过肾包膜下注射将载有 HDAC 抑制剂的微球递送至肾脏，以评估缺血再灌注诱导的 AKI 小鼠的治疗效果。体内结果表明，载有 HDAC 抑制剂的 Ca-ALG 微球可有效降低肾脏区域炎症反应和巨噬细胞浸润。总之，我们提出了一种有前途的治疗方法，该疗法具有有效的肾脏靶向药物递送来治疗 AKI。