Laser-Engineered Dissolving Microneedle Arrays for Transdermal Macromolecular Drug Delivery
Laser-Engineered Dissolving Microneedle Arrays for Transdermal Macromolecular Drug Delivery
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DOI：
10.1007/s11095-011-0419-4
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发表时间：
2011-08-01
影响因子：
3.7
通讯作者：
Donnelly, Ryan F.
中科院分区：
文献类型：
--
作者：
Migalska, Katarzyna;Morrow, Desmond I. J.;Donnelly, Ryan F.
为评价新型激光工程化溶解性微针（MN）的体外和体内透皮给药可行性，采用激光工程化模具，将20%w/w的聚甲基乙烯基醚马来酸酐（PMVE/MA）水溶液共混物制成含胰岛素的MN。为了研究胰岛素负载到MN中的构象变化，获得圆二色谱。使用Franz扩散池进行MN穿过新生猪皮肤的体外药物释放研究。通过糖尿病大鼠经皮给药和血糖水平的测量来评估MNs的体内效应。负载胰岛素的MNs构成模具尺寸的精确对应物。圆二色性分析表明，胰岛素在聚合物基质中的包封不会导致蛋白质二级结构的变化。体外研究表明，胰岛素转运通过新生猪皮肤显着增强。经皮给药的胰岛素加载MN阵列大鼠导致剂量依赖性的低血糖effects.We证明了从PMVE/MA的水混合物制备的MN在经皮给药的胰岛素的功效。我们目前正在研究皮肤中胰岛素的命运和MN介导的其他大分子的递送。
To assess the feasibility of transdermal macromolecule delivery using novel laser-engineered dissolving microneedles (MNs) prepared from aqueous blends of 20% w/w poly(methylvinylether maleic anhydride) (PMVE/MA) in vitro and in vivo.Micromoulding was employed to prepare insulin-loaded MNs from aqueous blends of 20% w/w PMVE/MA using laser-engineered moulds. To investigate conformational changes in insulin loaded into MNs, circular dichroism spectra were obtained. In vitro drug release studies from MNs across neonatal porcine skin were performed using Franz diffusion cells. The in vivo effect of MNs was assessed by their percutaneous administration to diabetic rats and measurement of blood glucose levels.MNs loaded with insulin constituted exact counterparts of mould dimensions. Circular dichroism analysis showed that encapsulation of insulin within polymeric matrix did not lead to change in protein secondary structure. In vitro studies revealed significant enhancement in insulin transport across the neonatal porcine skin. Percutaneous administration of insulin-loaded MN arrays to rats resulted in a dose-dependent hypoglycaemic effect.We demonstrated the efficacy of MNs prepared from aqueous blends of PMVE/MA in transdermal delivery of insulin. We are currently investigating the fate of the delivered insulin in skin and MN-mediated delivery of other macromolecules.