Diclofenac Enables Unprecedented Week-Long Microneedle-Enhanced Delivery of a Skin Impermeable Medication in Humans
Diclofenac Enables Unprecedented Week-Long Microneedle-Enhanced Delivery of a Skin Impermeable Medication in Humans
复制标题
DOI：
10.1007/s11095-013-1036-1
复制
发表时间：
2013-08-01
影响因子：
3.7
通讯作者：
Stinchcomb, Audra L.
中科院分区：
文献类型：
--
作者：
Brogden, Nicole K.;Banks, Stan L.;Stinchcomb, Audra L.
应用在皮肤上的微针会产生微孔，使药物能够通过皮肤传递不透水的化合物。第一个使用这项技术的人体研究表明，纳曲酮(一种阿片类拮抗剂)的释放时间为两到三天。然而，快速关闭微孔会钝化传递窗口。应用双氯芬酸(一种抗炎药物)可以在动物体内给予7天的纳曲酮。目前工作的目的是展示纳曲酮在人体内的一次微针治疗后的7天释放。受试者接受微针、双氯芬酸(或安慰剂)和纳曲酮的治疗。用阻抗测量作为替代标记来测量微孔的形成，并在微针应用后7天测量血浆纳曲酮浓度。从基线到微针治疗后，阻抗显著下降，证实了微孔的形成。第1组(双氯芬酸+纳曲酮，n=6)用纳曲酮治疗7d，第2组(安慰剂+纳曲酮，n=2)用药7h。在研究结束时，在第一组中，观察到完整皮肤和微针处理皮肤之间的阻抗显著差异(证实存在微孔)。这是第一项研究，证明在一次微针应用后持续一周的药物释放，这将增加患者的依从性，并允许对慢性病的治疗。
Microneedles applied to the skin create micropores, allowing transdermal drug delivery of skin-impermeable compounds. The first human study with this technique demonstrated delivery of naltrexone (an opioid antagonist) for two to three days. Rapid micropore closure, however, blunts the delivery window. Application of diclofenac (an anti-inflammatory) allows seven days of naltrexone delivery in animals. The purpose of the current work was to demonstrate delivery of naltrexone for seven days following one microneedle treatment in humans.Human subjects were treated with microneedles, diclofenac (or placebo), and naltrexone. Impedance measurements were used as a surrogate marker to measure micropore formation, and plasma naltrexone concentrations were measured for seven days post-microneedle application.Impedance dropped significantly from baseline to post-microneedle treatment, confirming micropore formation. Naltrexone was detected for seven days in Group 1 (diclofenac + naltrexone, n = 6), vs. 72 h in Group 2 (placebo + naltrexone, n = 2). At study completion, a significant difference in impedance was observed between intact and microneedle-treated skin in Group 1 (confirming the presence of micropores).This is the first study demonstrating week-long drug delivery after one microneedle application, which would increase patient compliance and allow delivery of therapies for chronic diseases.