California Northstate College of Pharmacy, Rancho Cordova, USA.
Drug Dev Ind Pharm. 2012 May;38(5):571-6. doi: 10.3109/03639045.2011.617753. Epub 2011 Oct 8.
This paper investigates the microneedle (MN) mediated in vitro transdermal iontophoretic delivery of prochlorperazine edisylate (PE) across dermatomed human skin. The Dermaroller™ induced microchannels were visualized using methylene blue staining and scanning electron microscopy. In vitro skin permeation studies were performed using vertical static Franz diffusion cells. Iontophoretic protocols involved application of direct current at a density of 0.4 mA/cm(2) using Ag as an anode and Ag/AgCl as a cathode. The effect of PE concentration (20, 50 and 100 mg/mL), number of passes of microneedles (0, 5, 10 and 20) on both iontophoretic and passive delivery of PE was studied. The Dermarollertm was found to successfully breach the skin barrier and a linear relationship (r(2) = 0.99) was observed between the number of passes of the Dermaroller™ and the number of microchannels created. Passive transdermal flux of PE (0.060 ± 0.003 µg/cm(2)/h) at 50 mg/mL donor PE concentration) was low and increased (4.15 ± 0.57 µg/cm(2)/h) with the application of direct current. Application of iontophoresis in conjunction with microneedle pre-treatment resulted in enhanced flux (4.90 ± 0.39 µg/cm(2)/h at 50 mg/mL donor PE concentration) of PE. The projected transdermal PE flux indicates that a 9 cm(2) patch could deliver PE in a sufficient amount to maintain therapeutic levels of the drug. In conclusion, microneedles when used in conjunction with iontophoresis significantly enhanced the transdermal delivery of PE and it may be feasible to develop an iontophoretic transdermal patch that could be integrated with MN.
本文研究了微针(MN)介导的普罗氯嗪乙二磺酸盐(PE)经皮离子电渗递送至去皮人体皮肤的体外情况。使用亚甲蓝染色和扫描电子显微镜观察 Dermaroller™诱导的微通道。使用垂直静态Franz 扩散细胞进行体外皮肤渗透研究。离子电渗协议涉及以 0.4 mA/cm(2)的密度施加直流电,其中 Ag 用作阳极,Ag/AgCl 用作阴极。研究了 PE 浓度(20、50 和 100 mg/mL)、微针穿过次数(0、5、10 和 20)对 PE 的离子电渗和被动传递的影响。Dermarollertm 被发现成功突破皮肤屏障,并且 Dermarollertm 的穿过次数与创建的微通道数量之间观察到线性关系(r(2) = 0.99)。在 50 mg/mL 供体 PE 浓度下,PE 的被动透皮通量(0.060 ± 0.003 µg/cm(2)/h)较低,并且随着直流电的施加而增加(4.15 ± 0.57 µg/cm(2)/h)。与微针预处理联合应用离子电渗时,PE 的通量增加(在 50 mg/mL 供体 PE 浓度下为 4.90 ± 0.39 µg/cm(2)/h)。PE 的经皮透皮通量表明,一个 9 cm(2)的贴片可以输送足够的 PE 以维持药物的治疗水平。总之,微针与离子电渗联合使用可显著增强 PE 的经皮传递,因此开发可与 MN 集成的离子电渗经皮贴片是可行的。