Abstract
Purpose.Dermal application of immunosuppressants can be an effective means of achieving site-specific immunosuppression (SITE) on skin allografts in burn wound management and in the treatment of various immune skin disorders. We have previously reported success with topical cyclosporine A (tCsA) in the treatment of skin allograft rejection in rats. Using a new tCsA formulation with a penetration enhancer (PE), polyethylene glycol-8 (PEG-8) glyceryl caprylate/caprate (Labrasol, Gattefossé, St. Priest, France), in a trinary drug delivery system, we hypothesized that we would induce SITE and significantly delay rejection of dual skin allografts in rats.Methods.Dual rat skin allografts from Lewis × Brown–Norway (LBN) donors were grafted to Lewis (Lew) recipients. Experimental animals (EXP,n= 7) received a 10-day course of systemic cyclosporine (sCsA, 8 mg/kg/day) followed by topical application. One of the two allografts on each experimental animal received tCsA/PE application (5 mg/kg/day) until sacrifice (tCsA/PE-treated). The other allograft received vehicle only (vehicle-treated). Allogeneic controls (ALLO-CON,n= 9) received no sCsA or tCsA. First signs of rejection were determined based on the initial observation of erythema, hair loss, flakiness, and/or scabs.Results.The mean time to rejection for ALLO-CON allografts was 6.3 ± 0.7 days (ttest,P= 0.0013); for vehicle-treated allografts, 12.3 ± 3.8 days (pairedttest,P= 0.0146); and for tCsA/PE-treated allografts, 25.6 ± 5.4 days. The disparity of days to rejection between dual allografts in the ALLO-CON group was 0.0 ± 0.0 day and that between the tCsA/PE- and vehicle-treated dual allografts was 13.3 ± 3.9 days (ttest,P= 0.0016).Conclusions.A new formulation of tCsA in a trinary drug delivery system is successful at delaying the onset of rejection in dual skin allografts in rats by SITE, and PEG-8 glyceryl caprylate/caprate may represent a potentially effective transdermal penetration enhancer.
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