Patel Hiren, Joshi Abhay, Joshi Amit, Stagni Grazia
a Division of Pharmaceutical Sciences , Arnold and Marie Schwartz College of Pharmacy, Long Island University , Brooklyn , NY , USA.
Drug Dev Ind Pharm. 2015;41(12):1962-7. doi: 10.3109/03639045.2015.1019353. Epub 2015 Mar 11.
Skin pretreatment with a microneedle roller (microporation (MP)) appears a simple and inexpensive technique to increase transdermal delivery of topically applied drug products. This study investigates the effect of MP on the passive and iontophoretic delivery of diclofenac (DCF) by quantifying dermis and plasma levels of DCF in a rabbit model. New Zealand albino female rabbits received either: (i) a topical application of 4 g of Voltaren® 1% gel with or without pretreatment with a microroller (0.5 mm needle length; density 23 microneedles per cm(2) area) or (ii) a DCF solution (40 mg/2.5 mL) via iontophoresis (IOMED transQ(E) medium size patch), with or without microroller pretreatment. A 300 µA/cm(2) cathodic current was applied for 20 min for a total of 80 mA. DCF concentrations were monitored in dermis with microdialysis sampling every 20 min for 5 h. Plasma samples were collected over the same period. In the passive delivery studies, microroller pretreatment increased Cmax by 1.5- and 2.0-fold in skin and plasma, respectively, and AUC by 1.5- and 2.4-fold in skin and plasma, respectively. In the iontophoresis delivery studies, microporation increased Cmax by 2.0-fold both in skin and in plasma, and AUC by 1.1- and 1.8-fold in skin and plasma, respectively. In conclusion, microneedle pretreatment increased significantly the systemic exposure of DCF from either passive or iontophoretic delivery, whereas the effect in skin was less pronounced.
用微针滚轮进行皮肤预处理（微孔透皮技术（MP））似乎是一种简单且经济的技术，可增加局部应用药物产品的透皮给药量。本研究通过定量兔模型中双氯芬酸（DCF）的真皮和血浆水平，研究微孔透皮技术对双氯芬酸被动和离子导入给药的影响。新西兰雌性白化兔接受以下处理：（i）局部应用4 g扶他林® 1%凝胶，使用或不使用微针滚轮进行预处理（针长0.5 mm；每平方厘米面积23根微针的密度）；或（ii）通过离子导入法（IOMED transQ(E)中型贴片）给予DCF溶液（40 mg/2.5 mL），使用或不使用微针滚轮预处理。施加300 μA/cm²的阴极电流20分钟，总电量为80 mA。每20分钟用微透析采样监测真皮中的DCF浓度，持续5小时。在同一时期收集血浆样本。在被动给药研究中，微针滚轮预处理使皮肤和血浆中的Cmax分别增加了1.5倍和2.0倍，皮肤和血浆中的AUC分别增加了1.5倍和2.4倍。在离子导入给药研究中，微孔透皮技术使皮肤和血浆中的Cmax均增加了2.0倍，皮肤和血浆中的AUC分别增加了1.1倍和1.8倍。总之，微针预处理显著增加了DCF被动或离子导入给药后的全身暴露量，而对皮肤的影响则不太明显。
