Microneedle-array patch with pH-sensitive formulation for glucose-responsive insulin delivery
Microneedle-array patch with pH-sensitive formulation for glucose-responsive insulin delivery
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DOI：
10.1007/s12274-020-3273-z
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发表时间：
2021-01-05
期刊：
影响因子：
9.9
通讯作者：
Du, Jin-Zhi
中科院分区：
文献类型：
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作者：
Luo, Feng-Qin;Chen, Guojun;Du, Jin-Zhi
葡萄糖响应型胰岛素给药系统在改善糖尿病患者的治疗效果和生活质量方面显示出巨大的潜力。本文中，构建了一种新的微针阵列贴片，其含有pH敏感的负载胰岛素的纳米颗粒（NP）（SNP（I））以及葡萄糖氧化酶（GOx）-和过氧化氢酶（CAT）-负载pH不敏感的NP（iSNP（G+C）），用于经皮葡萄糖响应性胰岛素递送。SNP（I）是由pH敏感的两亲性嵌段共聚物通过双重乳液制备的，并在高血糖条件下在由iSNP（G+C）中的GOx诱导的温和酸性环境下经历快速解离以促进胰岛素释放。iSNP（G+C）中的CAT可以进一步消耗GOx氧化过程中产生的过量H2 O2，从而降低正常皮肤炎症的风险。对1型糖尿病小鼠的体内研究表明，该平台可以长期有效地将血糖水平调节在正常范围内。
Glucose-responsive insulin delivery systems show great promise to improve therapeutic outcomes and quality of life for people with diabetes. Herein, a new microneedle-array patch containing pH-sensitive insulin-loaded nanoparticles (NPs) (SNP(I)) together with glucose oxidase (GOx)- and catalase (CAT)-loaded pH-insensitive NPs (iSNP(G+C)) is constructed for transcutaneous glucose-responsive insulin delivery. SNP(I) are prepared via double emulsion from a pH-sensitive amphiphilic block copolymer, and undergo rapid dissociation to promote insulin release at a mild acidic environment induced by GOx in iSNP(G+C) under hyperglycemic conditions. CAT in iSNP(G+C) can further consume excess H2O2 generated during GOx oxidation, and thus reduce the risk of inflammation toward the normal skin. The in vivo study on type 1 diabetic mice demonstrates that the platform can effectively regulate blood glucose levels within normal ranges for a prolonged period.