The Influence of Metabolism on Percutaneous Absorption of Cyclosporin-A

Abstract

Our previous reports using hairless mouse skin model showed that topical delivery of cyclosporin-A (CsA) could be achieved and controlled with nonionic liposomal and nonionic lipid-based formulations composed of glyceryl dilaurate (GDL), cholesterol (CH), and polyoxyethylene-10-stearyl ether (POE-10) at varying weight ratios (1,2). However, the distribution profiles were obtained using radiolabeled CsA and thus could represent intact drug as well as its metabolites. The present studies aim to investigate if the previously reported profiles actually represented intact CsA. The studies were carried out using a “high-pressure” liquid chromatography (HPLC) method and in vitro skin deposition studies with a metabolic inhibitor (sodium azide) incorporated in the receptor fluid. The results indicated that skin metabolism of CsA and hence its effect on percutaneous absorption of CsA is minimal and that the CsA distribution profiles obtained using radiolabeled CsA represented distribution of intact drug and not its metabolites.

Keywords::

• Cyclosporin-A
• Cutaneous metabolism
• Percutaneous absorption
• Topical delivery