Investigation into the Potential of Electroporation Facilitated Topical Delivery of Cyclosporin A

Abstract

Purpose: The potential for electroporation-facilitated topical transport of cyclosporin A (CysA) was investigated using rat skin. Methods: 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. Results: 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. Conclusion: 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.