Site-Specific Immunosuppression using a New Formulation of Topical Cyclosporine A with Polyethylene Glycol-8 Glyceryl Caprylate/Caprate
| Autor: | Dipak Malli, Charles W. Hewitt, Hoang S. Tran, Francis A. Chrzanowski, Martha S. Matthews, Matthew M. Puc |
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| Rok vydání: | 1999 |
| Předmět: |
Graft Rejection
medicine.medical_specialty Erythema Administration Topical medicine.medical_treatment Urology Skin Diseases Polyethylene Glycols Immune system Rats Inbred BN Animals Transplantation Homologous Medicine Polyethylene glycol-8 glyceryl caprylate Immunosuppression Therapy business.industry Graft Survival Penetration enhancer Immunosuppression Skin Transplantation medicine.disease Rats Surgery Transplantation surgical procedures operative Hair loss Rats Inbred Lew Drug delivery Cyclosporine Caprylates medicine.symptom Burns business Immunosuppressive Agents |
| Zdroj: | Journal of Surgical Research. 83:136-140 |
| ISSN: | 0022-4804 |
| DOI: | 10.1006/jsre.1999.5582 |
| Popis: | 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, Gattefosse, 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. |
| Databáze: | OpenAIRE |
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