College of Chemical Engineering, Huaqiao University, Xiamen, 361021, China.
Department of Chemistry, Xinxiang Medical University, Xinxiang, 453003, Henan, China.
J Nanobiotechnology. 2020 Jul 14;18(1):96. doi: 10.1186/s12951-020-00652-z.
The traditional treatment for diabetes usually requires frequent insulin injections to maintain normoglycemia, which is painful and difficult to achieve blood glucose control.
To solve these problems, a non-invasive and painless oral delivery nanoparticle system with bioadhesive ability was developed by amphipathic 2-nitroimidazole-L-cysteine-alginate (NI-CYS-ALG) conjugates. Moreover, in order to enhance blood glucose regulation, an intelligent glucose-responsive switch in this nanoparticle system was achieved by loading with insulin and glucose oxidase (GOx) which could supply a stimulus-sensitive turnover strategy. In vitro tests illustrated that the insulin release behavior was switched "ON" in response to hyperglycemic state by GOx catalysis and "OFF" by normal glucose levels. Moreover, in vivo tests on type I diabetic rats, this system displayed a significant hypoglycemic effect, avoiding hyperglycemia and maintaining a normal range for up to 14 h after oral administration.
The stimulus-sensitive turnover strategy with bioadhesive oral delivery mode indicates a potential for the development of synthetic GR-NPs for diabetes therapy, which may provide a rational design of proteins, low molecular drugs, as well as nucleic acids, for intelligent releasing via the oral route.
传统的糖尿病治疗方法通常需要频繁注射胰岛素来维持血糖正常，这既痛苦又难以实现血糖控制。
为了解决这些问题，通过两亲性 2-硝基咪唑-L-半胱氨酸-藻酸盐（NI-CYS-ALG）缀合物开发了具有生物黏附能力的非侵入性和无痛的口服递药纳米粒子系统。此外，为了增强血糖调节，通过装载胰岛素和葡萄糖氧化酶（GOx）在该纳米粒子系统中实现了智能葡萄糖响应开关，其可以提供刺激敏感的转换策略。体外试验表明，GOx 催化下的高血糖状态会使胰岛素释放行为“开启”，而正常血糖水平会使胰岛素释放行为“关闭”。此外，在 I 型糖尿病大鼠的体内试验中，该系统表现出显著的降血糖作用，可避免高血糖，并在口服给药后长达 14 小时内维持正常范围。
具有生物黏附性口服递药模式的刺激敏感转换策略表明了用于糖尿病治疗的合成 GR-NPs 的发展潜力，这可能为通过口服途径智能释放蛋白质、低分子药物以及核酸提供了合理的设计。
