Topical Delivery of Cyclosporin a Coevaporate Using Electroporation Technique

Abstract

The immunosuppressive drug cyclosporin A (CSA) is useful in treating psoriasis. However, the systemic use of CSA is fraught with the problem of toxicities. The best way to treat psoriasis would be to deliver CSA topically but no such formulation is currently available. The highly lipophilic nature and the large molecular weight of CSA are the main hurdles in developing an efficient topical formulation. Attempts were made in our laboratory to deliver CSA topically using electroporation technique. First, the aqueous dissolution of CSA was improved by preparing a coevaporate using polyvinyl ethyl methyl ether maleic acid copolymer, which resulted in a 9.5-fold increase in the aqueous solubility of CSA. Subsequently, the aqueous solution of the coevaporate was used as the donor solution to deliver CSA transdermally in a rat skin model, using single and multiple pulse electroporation. Use of single pulse mode at a field strength 200 V/cm- and 10-msec pulse interval, resulted in delivering 87 ng of CSA per 0.87 cm² of the rat skin. This was a significant increase by a factor of 8.5 in the delivery of CSA, when compared to the passive diffusion. The amount of CSA delivered to the skin using electroporation may be further enhanced by increasing the thermodynamic activity of CSA in the donor solution. The other electroporation variables which need to be further optimized include field strength, pulse length, and number of pulses.