Topical Application of Liposomally Entrapped Ciclosporin Evaluated by in vitro Diffusion Studies with Human Skin

Abstract

The kinetics and extent of uptake of ciclosporin (CSA) in various strata of human cadaver skin upon topical application of several CSA formulations were determined by in vitro diffusion cell experiments. The CSA formulations tested included an oil-in-water emulsion and four liposomal systems. The accumulation of CSA in the stratum corneum at 24 h is in the order: ‘skin lipid’ multilamellar liposomes (MLV) > phospholipid MLV ≈ ‘skin lipid’ large unilamellar liposomes (LUV) > phospholipid LUV > > > emulsion. The total amount of drug in the deeper stratum corneum and deeper skin strata at 24 h is in the order: phospholipid MLV > ‘skin lipid’ MLV > phospholipid LUV > ‘skin lipid’ LUV > emulsion. Whereas ‘skin lipid’ liposomes were more effective than phospholipid-based liposomes in depositing drug in deeper skin strata for rodent species (mouse and guinea pig), the opposite effect was observed for human cadaver skin. More importantly, all the liposomal formulations tested were far more effective than the emulsion formulation in depositing CSA into the skin.