糖尿病是一种由于患者胰岛素分泌功能缺失或受损而导致的以高血糖为主要特征的代谢性疾病。根据国际糖尿病联合会的调查显示,全世界糖尿病患者的人数已超过5.37亿。目前对于I型和重症II型糖尿病的治疗需要每日注射2~4次胰岛素以维持正常血糖水平,这给患者带来注射的疼痛和生活不便,同时由于无法按需要实时给予合适剂量的胰岛素,存在过量给药的低血糖风险。葡萄糖响应微针贴可根据血糖水平自适应调节胰岛素释放速率,在糖尿病治疗领域受到广泛关注。
Figure 1. (a) The formation of a MNP. (b) The glucose-responsive insulin-releasing mechanism and the corresponding influence factors. (c) The illustration for the blood-glucose regulating performance of a MNP.
体外胰岛素释放实验结果表明,通过优化FPBA-PL/PVA比例以及FPBA-PL中FPBA的接枝率显著提高了胰岛素释放的葡萄糖响应灵敏性(Figure 2)。
Figure 2. The cumulative-releasing tests for FITC-INS-loaded (a) MNP-1, (b) MNP-2, (c) MNP-3, (d) MNP-4, (e) MNP-5 and (f) MNP-6. (g) The comparison result among MNP-i and the previously reported phenylborate-ester-crosslinked MNPs. (h) The INS-releasing performance of MNP-5 under the changing glucose concentrations. (i) The 11B spectra to study the formation of phenylborate esters. (j) The formation of the phenylborate esters. The data of (a)-(f) and (h) were shown as the means ± SD (n = 3).
Figure 3. (a1) A piece of GR-MNP was inserted in the rat skin and fixed by the TegadermTM film. (a2) The photos of the microneedle-induced micro-pores (scale bar = 2 mm) and the trypan-blue-staining result. (a3) The H & E-staining section of the microneedle-inserted skin (scale bar = 50 μm). (b) The anti-hypoglycemia test on the healthy rats and (c) the corresponding analytic result. (d) The BGL-lowering test on the diabetic rats and (e) the corresponding plasma INS levels. (f) The IPGTT schedule, (g) the IPGTT results and (h) the corresponding analytic result. (i) The plasma-INS curves in IPGTT with the statistical analysis between “nGR-MNP” and “GR-MNP” and (j) the corresponding analytic result. (k) The BGL-controlling test under the mimic three-meal-per-day mode. All the data of (b)-(e) and (g)-(k) were shown as the means ± SD (n = 5). The statistical analyses were performed by two-tailed Student’s t-test. * P < 0.05, ** P < 0.01 and *** P < 0.001.
以上成果近期发表在ACS Applied Materials & Interfaces上,论文题为“Electrostatic-interaction-aided microneedle patch for enhanced glucose-responsive insulin delivery and three-meal-per-day blood-glucose regulation”。论文的第一作者为浙江大学化学工程与生物工程学院博士研究生沈迪,通讯作者为浙江大学化学工程与生物工程学院俞豪杰教授。
论文信息:ACS Appl. Mater. Interfaces 2024, 16, 4449-4461
论文链接:https://doi.org/10.1021/acsami.3c16540
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