TOPICAL DELIVERY OF CYCLOSPORINE-A COEVAPORATE USING ELECTROPORATION TECHNIQUE

The immunosuppressive drug cyclosporin A (CSA) is useful in treating p soriasis. However, the systemic use of CSA is fraught with the problem of toxicities. The best way to treat psoriasis would be to deliver CS A 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 prepa ring a coevaporate using polyvinyl ethyl methyl ether maleic acid copo lymer, which resulted in a 9.5-fold increase in the aqueous solubility of CSA. Subsequently, the aqueous solution of the coevaporate was use d as the donor solution to deliver CSA transdermally in a rat skin mod el, using single and multiple pulse electroporation. Use of single pul se mode at a field strength 200 V/cm- and 10-msec pulse interval, resu lted in delivering 87 ng of CSA per 0.87 cm(2) of the rat skin. This w as a significant increase by a factor of 8.5 in the delivery of CSA, w hen compared to the passive diffusion. The amount of CSA delivered to the skin using electroporation may be further enhanced by increasing t he thermodynamic activity of CSA in the donor solution. The other elec troporation variables which need to be further optimized include field strength, pulse length, and number of pulses.