CICECO - Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.
UCIBIO, REQUIMTE, MedTech - Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
Carbohydr Polym. 2020 Aug 1;241:116314. doi: 10.1016/j.carbpol.2020.116314. Epub 2020 Apr 30.
The present study reports the fabrication of dissolvable microneedle (MN) patches using pullulan (PL), a water-soluble polysaccharide with excellent film-forming ability, for the transdermal administration of insulin, envisioning the non-invasive treatment of diabetes. PL MNs patches were successfully prepared by micromoulding and revealed good thermal stability (T = 294 °C) and mechanical properties (>0.15 N needle), penetrating skin up to 381 μm depth, as revealed by in vitro skin tests. After application into human abdominal skin in vitro, the MNs dissolved within 2 h releasing up to 87% of insulin. When stored at 4, 20 and 40 °C for 4 weeks, insulin was able to retain its secondary structure, as shown by circular dichroism spectropolarimetry. The prepared PL MNs were non-cytotoxic towards human keratinocytes, being suitable for skin application. These findings suggest that PL MNs have potential to deliver insulin transdermally, thus avoiding its subcutaneous administration.
本研究报告了使用具有优异成膜能力的水溶性多糖普鲁兰（PL）制造可溶解微针（MN）贴片，用于胰岛素的透皮给药，期望实现糖尿病的非侵入性治疗。通过微成型成功制备了 PL MN 贴片，表现出良好的热稳定性（T=294°C）和机械性能（>0.15 N 针），在体外皮肤测试中，微针可穿透皮肤达 381μm 深度。在体外应用于人体腹部皮肤后，MNs 在 2 小时内溶解，释放高达 87%的胰岛素。当在 4、20 和 40°C 下储存 4 周时，胰岛素通过圆二色性光谱偏振法能够保留其二级结构。所制备的 PL MNs 对人角质形成细胞无细胞毒性，适合皮肤应用。这些发现表明，PL MNs 有可能经皮递送胰岛素，从而避免其皮下给药。
