Skin microchannels (MCs) created by microneedles (MNs) provide a promising route for enhancing transdermal drug delivery. This study investigated passive and iontophoretic transport of pramipexole dihydrochloride (PXCl) across skin MCs created by polymer MN patches made of 1:2 polymethyl-vinyl-ether-co-maleic acid (PMVEMA) to polyvinyl alcohol (PVA) ratio. Permeation studies were performed in vitro using excised human skin under the conditions of (i) “poke-and-patch” and “poke-and-release” delivery approaches with varying concentration of PXCl in the formulations, (ii) drug-loaded dissolving MN (DMN) and hydrogel-forming MN (HGMN) type patches and (iii) combination of MNs and iontophoresis. The results showed that DMN patch greatly enhanced transdermal delivery of PXCl for both “poke-and-patch” and “poke-and-release” approaches as compared with the conventional delivery method. PXCl flux mainly resulted from the contribution of MC pathway created in skin and increased with increasing drug amounts in the formulations. Compared to DMN patch, HGMN patch provided more linear sustained drug delivery over 72 h. Electromigration was the main mechanism of PXCl iontophoresis through MCs and flux enhancement was found to be larger for HGMN patch than DMN patch. These results demonstrated the potential application of MN patches individually or combined with iontophoresis as an alternative method for PXCl administration.

由微针 (MNs) 创建的皮肤微通道 (MCs) 为增强透皮给药提供了一条有前途的途径。本研究调查了普拉克索二盐酸盐 (PXCl) 通过由 1:2 聚甲基-乙烯基-醚-共-马来酸 (PMVEMA) 与聚乙烯醇 (PVA) 比例制成的聚合物 MN 贴片产生的皮肤 MC 的被动和离子电渗传输。在体外进行渗透研究在以下条件下使用切除的人体皮肤：（i）“戳-贴”和“戳-释放”递送方法，在制剂中使用不同浓度的 PXCl，（ii）载药溶解 MN（DMN）和水凝胶-形成 MN (HGMN) 型贴片和 (iii) MNs 和离子电渗疗法的组合。结果表明，与传统递送方法相比，DMN 贴剂大大增强了 PXCl 的“戳贴”和“戳放”方法的透皮递送。PXCl 通量主要来自皮肤中产生的 MC 途径的贡献，并随着制剂中药物量的增加而增加。与 DMN 贴片相比，HGMN 贴片在 72 小时内提供了更线性的持续药物递送。电迁移是 PXCl 离子电渗通过 MC 的主要机制，发现 HGMN 贴片的通量增强大于 DMN 贴片。这些结果证明了单独使用 MN 贴剂或与离子电渗疗法相结合作为 PXCl 给药的替代方法的潜在应用。