Synergistic penetration enhancement effect of ethanol and phospholipids on the topical delivery of cyclosporin A

Abstract

In the present study, ethanol was used with a commercially available lipid mixture, NAT 8539, to improve the topical delivery of cyclosporin A (CyA). The vesicles formed from this solution ranged from 56.6 to 100.6 nm in diameter, depending on the amount of ethanol added in the formulation. In-vitro skin penetration studies were carried out with Franz diffusion cell using human abdominal skin. There was a decrease in average size of vesicles, as the amount of ethanol in formulation increased from 0% to 3.3% and a further addition of ethanol resulted in an increase in average diameter of vesicles. CyA vesicles containing 10% and 20% ethanol showed statistically enhanced deposition of CyA into the stratum corneum (SC), as compared to vesicles prepared without ethanol. CyA vesicles prepared with NAT 8539/ethanol (10/3.3) showed a 2.1-fold, CyA vesicles with NAT 8539/ethanol (10/10) showed a 4.4-fold, and CyA vesicles with NAT 8539/ethanol (10/20) showed a 2.2-fold higher deposition of CyA into SC, as compared to vesicles made of NAT 8539 without ethanol [NAT 8539/ethanol (10/0)]. The efficiency of the formulations was sequenced in the order of: NAT 8539/ethanol (10/10)>NAT 8539/ethanol (10/20)>NAT 8539/ethanol (10/3.3)>ethanol>NAT 8539/ethanol (10/0). These results can be considered a step forward for the topical delivery of problematic molecules like CyA using liposomes as a tool for the treatment of inflammatory skin diseases like psoriasis, atopic dermatitis, and diseases of the hair follicle like alopecia areata, etc.