Xu Bin, Jiang Guohua, Yu Weijiang, Liu Depeng, Zhang Yang, Zhou Junyi, Sun Shiqing, Liu Yongkun
Department of Polymer Materials, Zhejiang Sci Tech University, Hangzhou 310018, China.
J Mater Chem B. 2017 Nov 7;5(41):8200-8208. doi: 10.1039/c7tb02082a. Epub 2017 Oct 9.
A glucose-mediated insulin delivery system would be highly satisfactory for diabetes diagnosis dependent on the concentration of blood glucose in the body. Herein, a novel microneedle (MN) delivery device integrated with insulin-loaded and HO-responsive mesoporous silica nanoparticles (MSNs) was designed to achieve fast and painless administration. The MSNs were obtained by the modification by 4-(imidazoyl carbamate)phenylboronic acid pinacol ester (ICBE) and following a host-guest complexation between ICBE and α-cyclodextrin (α-CD). A drug and a glucose-responsive factor, namely insulin and glucose oxidase (GO), were encapsulated into the MSNs. GO in the MSNs could convert glucose to gluconic acid and generate hydrogen peroxide (HO). The phenylboronic ester on the surface of the MSNs could be oxidized in the presence of HO, which resulted in the destruction of host-guest complexation, leading to the disassembly of the drug-loaded MSNs and subsequent release of the preloaded insulin. After transdermal administration to diabetic rats, an effective hypoglycemic effect was obtained by detection over time compared with that of subcutaneous injection. This work suggests that the as-prepared glucose-mediated and HO-responsive MN systems have promising applications in diabetes treatment.
对于依赖体内血糖浓度的糖尿病诊断而言，葡萄糖介导的胰岛素递送系统将是非常令人满意的。在此，设计了一种集成有负载胰岛素和对过氧化氢（HO）响应的介孔二氧化硅纳米颗粒（MSN）的新型微针（MN）递送装置，以实现快速且无痛的给药。通过用4 -（咪唑基氨基甲酸酯）苯硼酸频哪醇酯（ICBE）进行修饰，然后使ICBE与α-环糊精（α-CD）进行主客体络合来获得MSN。将药物和葡萄糖响应因子，即胰岛素和葡萄糖氧化酶（GO）封装到MSN中。MSN中的GO可将葡萄糖转化为葡萄糖酸并产生过氧化氢（HO）。MSN表面的苯硼酸酯在HO存在下可被氧化，这导致主客体络合被破坏，从而导致载药MSN解体并随后释放预先装载的胰岛素。对糖尿病大鼠进行经皮给药后，与皮下注射相比，通过随时间检测获得了有效的降血糖效果。这项工作表明，所制备的葡萄糖介导且对HO响应的MN系统在糖尿病治疗中具有广阔的应用前景。
