Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne, Victoria, 3004, Australia.
School of Science, RMIT University, Melbourne, Victoria, 3000, Australia.
Adv Mater. 2023 May;35(21):e2210392. doi: 10.1002/adma.202210392. Epub 2023 Mar 12.
Glucose-responsive insulin-delivery platforms that are sensitive to dynamic glucose concentration fluctuations and provide both rapid and prolonged insulin release have great potential to control hyperglycemia and avoid hypoglycemia diabetes. Here, biodegradable and charge-switchable phytoglycogen nanoparticles capable of glucose-stimulated insulin release are engineered. The nanoparticles are "nanosugars" bearing glucose-sensitive phenylboronic acid groups and amine moieties that allow effective complexation with insulin (≈95% loading capacity) to form nanocomplexes. A single subcutaneous injection of nanocomplexes shows a rapid and efficient response to a glucose challenge in two distinct diabetic mouse models, resulting in optimal blood glucose levels (below 200 mg dL ) for up to 13 h. The morphology of the nanocomplexes is found to be key to controlling rapid and extended glucose-regulated insulin delivery in vivo. These studies reveal that the injected nanocomplexes enabled efficient insulin release in the mouse, with optimal bioavailability, pharmacokinetics, and safety profiles. These results highlight a promising strategy for the development of a glucose-responsive insulin delivery system based on a natural and biodegradable nanosugar.
可响应葡萄糖的胰岛素输送平台对动态葡萄糖浓度波动敏感，并能实现快速和持续的胰岛素释放，具有很好的控制高血糖和避免低血糖的潜力。在这里，设计了一种可响应葡萄糖的生物可降解和电荷可转换的植物糖原纳米颗粒，用于胰岛素的释放。这些纳米颗粒是“纳米糖”，带有葡萄糖敏感的苯硼酸基团和胺基，能够与胰岛素有效络合（≈95%的载药能力）形成纳米复合物。在两种不同的糖尿病小鼠模型中，单次皮下注射纳米复合物对葡萄糖刺激有快速而有效的反应，使血糖水平（低于 200mg/dL）在长达 13 小时内保持最佳。研究发现，纳米复合物的形态是控制体内快速和持续的葡萄糖调节胰岛素输送的关键。这些研究结果表明，所注射的纳米复合物在小鼠体内能够实现高效的胰岛素释放，具有最佳的生物利用度、药代动力学和安全性。这些结果突出了一种基于天然和可生物降解的纳米糖的葡萄糖响应性胰岛素输送系统的有前途的策略。
