title: Percutaneous absorption and dermal delivery of cyclosporin A.
abstract: The present study deals with attempts to deliver cyclosporin A into the deeper skin and some of the fundamental reasons why this proves so difficult. Because of different physicochemical requirements for the solution and activity of cyclosporin A and the enhancer, n-decylmethyl sulfoxide, it was hard to demonstrate increases in permeation of cyclosporin A by the enhancer in either aqueous or ethanol/water formulation. Cyclosporin A was prohibitively insoluble in aqueous media and the activity of the enhancer is diminished to ineffectiveness when it is applied in alcoholic media. However, n-decylmethyl sulfoxide action on the stratum corneum could be obtained by pretreating the skin. The effect of pretreatment with this compound on the permeation of cyclosporin A through hairless mouse skin and human skin was studied with side-by-side diffusion cells. The skin was pretreated with 10 mM n-decylmethyl sulfoxide for various durations. Cyclosporin A in an ethanol/water formulation was then placed in the donor cell, with the amount of ethanol being controlled to maintain the highest possible thermodynamic activity. Accumulations of cyclosporin A in receiver cell media, aqueous or ethanol/water, were then assessed. Permeation from two different concentrations of cyclosporin A was compared. The permeability of hairless mouse skin to cyclosporin A was increased by the pretreatment, but results with human skin were more equivocal. It appears that it will take very long pretreatments to ready human skin for topical cyclosporin A therapy.
authors.affiliation: College of Pharmacy, University of Michigan, Ann Arbor 48109-1065, USA.
authors.forename: H K
authors.initials: HK
authors.lastname: Choi
authors.forename: G L
authors.initials: GL
authors.lastname: Flynn
authors.forename: G L
authors.initials: GL
authors.lastname: Amidon
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects; D013997:Time Factors; D014867:Water
chemical_list: D014867:Water; C054274:1-decyl methyl sulfoxide; D016572:Cyclosporine; D004121:Dimethyl Sulfoxide