Liu Hong-Zhuo, Wang Yong-Jun, Xu Lu, Li San-Ming
School of Pharmaceutics, Pharmaceutical University of Shenyang, Shenyang, People's Republic of China.
PDA J Pharm Sci Technol. 2010 May-Jun;64(3):191-9.
The potential for electroporation-facilitated topical transport of cyclosporin A (CysA) was investigated using rat skin.
Studies of various electrical factors acting on the deposition of CysA into the stratum corneum and deeper skin of in vitro electroporation were performed. We also tested the synergistic effect of electroporation and other approaches such as chemical enhancers and low-frequency ultrasound on topical drug delivery of CysA.
Electroporation increased the amount of CysA retained in the skin by only 3 times that of passive diffusion. We found that the efficacy of electroporation in enhancing topical delivery can be further increased by pretreatment of skin with chemical enhancers, such as Azone and menthol. Meanwhile, only a small amount was seen to transport across the full skin into the receiver compartment. Trimodality treatment comprised of pretreatment with Azone and ultrasound in combination followed by electroporation was not effective in enhancing the topical delivery of CysA. However, this combination strategy increased the penetration of CysA through rat skin by an order of 15.
In general, the enhanced skin accumulation of CysA by the combination of electroporation and chemical enhancers could help significantly to optimize the targeting of the drug without a concomitant increase in systemic side effects.
使用大鼠皮肤研究电穿孔促进环孢素A（CysA）经皮转运的潜力。
进行了各种电因素对体外电穿孔过程中CysA在角质层和更深层皮肤中沉积作用的研究。我们还测试了电穿孔与其他方法（如化学增强剂和低频超声）对CysA经皮给药的协同作用。
电穿孔使皮肤中保留的CysA量仅增加至被动扩散的3倍。我们发现，用化学增强剂（如氮酮和薄荷醇）预处理皮肤可进一步提高电穿孔增强经皮给药的效果。同时，仅有少量药物穿过全层皮肤进入接受室。由氮酮预处理和超声联合后再进行电穿孔组成的三联疗法在增强CysA经皮给药方面无效。然而，这种联合策略使CysA透过大鼠皮肤的渗透增加了15倍。
总体而言，电穿孔与化学增强剂联合可增强CysA在皮肤中的蓄积，这有助于在不增加全身副作用的情况下显著优化药物靶向性。
