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红细胞模拟皮下平台,采用激光控制技术治疗糖尿病。

Erythrocyte-mimicking subcutaneous platform with a laser-controlled treatment against diabetes.

机构信息

School of Public Health, Nantong University, Nantong, Jiangsu 226019, PR China.

Institute of Materials Engineering, College of Engineering and Applied Sciences, Nanjing University, Jiangsu 210093, PR China.

出版信息

J Control Release. 2022 Jan;341:261-271. doi: 10.1016/j.jconrel.2021.11.021. Epub 2021 Nov 16.

Abstract

Exogenous insulin (INS) is critical for managing diabetes. However, owing to its short in vivo half-life, frequent injection of INS is un-avoidable, which is both painful and inconvenient, compromising the quality of life. Herein, we developed a laser-regulated INS release system (INS-ICG@ER hydrogel) that allowed an on-demand release of INS from the subcutaneous INS reservoir by remote laser control without the frequent injection of INS. The amino acid hydrogel functions as a hydrogel 3D scaffold material, which offers increased subcutaneous stability of drug loaded erythrocytes (ER). This INS-ICG@ER hydrogel would release INS due to the elevated content of reactive oxygen species (ROS), generated by ICG under laser irritation. Conversely, the ROS would be scavenged without the laser irradiation and stopped the release of INS from INS-ICG@ER hydrogel. Furthermore, the release of INS from INS-ICG@ER hydrogel could be regulated by laser irradiation. The INS-ICG@ER hydrogels could control the hyperglycemia within 2 h in diabetic mice and maintained their normal blood glucose level (BGL) for up to 6 days with laser irradiation 30 min prior to meals avoiding the frequent injection of free INS. This delivery system is an effective method that offers a spatiotemporally controlled release of INS to control the glucose level in vivo.

摘要

外源性胰岛素(INS)对于糖尿病的治疗至关重要。然而,由于其体内半衰期短,不可避免地需要频繁注射 INS,这既痛苦又不方便,影响了生活质量。在此,我们开发了一种激光调控的 INS 释放系统(INS-ICG@ER 水凝胶),通过远程激光控制,从皮下 INS 储库中按需释放 INS,无需频繁注射 INS。氨基酸水凝胶作为一种水凝胶 3D 支架材料,增加了负载红细胞(ER)的 INS 的皮下稳定性。这种 INS-ICG@ER 水凝胶由于 ICG 在激光刺激下产生的活性氧(ROS)含量升高而释放 INS。相反,没有激光照射时,ROS 会被清除,从而阻止 INS 从 INS-ICG@ER 水凝胶中释放。此外,激光照射可以调节 INS 的释放。INS-ICG@ER 水凝胶可在 2 小时内控制糖尿病小鼠的高血糖,并在餐前 30 分钟激光照射后,将其血糖水平(BGL)维持在正常水平长达 6 天,避免了频繁注射游离 INS。该递药系统是一种有效的方法,可实现 INS 的时空控制释放,从而控制体内血糖水平。

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