Key Laboratory of Advanced Textile Materials and Manufacturing Technology (ATMT) , Ministry of Education , Hangzhou 310018 , China.
National Engineering Laboratory for Textile Fiber Materials and Processing Technology (Zhejiang) , Hangzhou 310018 , China.
ACS Appl Mater Interfaces. 2018 Jun 13;10(23):20014-20024. doi: 10.1021/acsami.8b04484. Epub 2018 May 31.
Herein, a dual-responsive insulin delivery device by integrating glucose- and HO-responsive polymeric vesicles (PVs) with transcutaneous microneedles (MNs) has been designed. This novel microneedle delivery device achieves a goal of fast response, excellent biocompatibility, and painless administration. The PVs are self-assembled from a triblock copolymer including poly(ethylene glycol), poly(phenylboronic acid) (glucose-sensitive block), and poly(phenylboronic acid pinacol ester) (HO-sensitive block). After loading with insulin and glucose oxidase (GO ), the drug-loaded PVs display a basal insulin release as well as a promoted insulin release in response to hyperglycemic states. The insulin release rate responds quickly to elevated glucose and can be further promoted by the incorporated GO , which will generate the HO at high glucose levels and further break the chemical links of phenylboronic acid pinacol ester group. Finally, the transdermal delivery of insulin to the diabetic rats ((insulin + GO )-loaded MNs) presents an effective hypoglycemic effect compared to that of subcutaneous injection or only insulin-loaded MNs, which indicates the as-prepared MNs insulin delivery system could be of great importance for the applications in the therapy of diabetes.
本文设计了一种通过将葡萄糖和 HO 响应性聚合物囊泡 (PVs) 与经皮微针 (MNs) 集成来实现胰岛素递药的双重响应性装置。这种新型的微针给药装置实现了快速响应、良好的生物相容性和无痛给药的目标。PVs 由包括聚乙二醇、聚苯硼酸 (葡萄糖敏感嵌段) 和聚苯硼酸频哪醇酯 (HO 敏感嵌段) 的三嵌段共聚物自组装而成。负载胰岛素和葡萄糖氧化酶 (GO) 后，载药 PVs 在高血糖状态下显示出基础胰岛素释放和促进的胰岛素释放。胰岛素释放速率对葡萄糖升高的响应迅速，并可进一步被掺入的 GO 促进，GO 将在高葡萄糖水平下产生 HO，进一步破坏频哪醇酯基团的硼酸苯酯键。最后，与皮下注射或仅负载胰岛素的 MNs 相比，糖尿病大鼠的胰岛素经皮递送 (负载胰岛素和 GO 的 MNs) 呈现出有效的降血糖作用，这表明所制备的 MNs 胰岛素给药系统在糖尿病治疗应用中具有重要意义。
