Novel Experimental System as an Alternative to Animal Experiments to Study the Skin Permeation of Drugs

Toshinobu Seki, Tatsuya Sashida, Shinji Oshima, Yuya Egawa, Hiroko Nakagawa, Osamu Hosoya and Kazuhiko Juni

Faculty of Pharmaceutical Sciences, Josai University

AATEX 14(2):887-897, 2009

A skin-mimicking artificial membrane consisting of a silicone membrane as a model stratum corneum and laminated dialysis membranes as a model of viable skin was prepared to imitate the layered structure of skin. The permeability of flurbiprofen (FP) through the laminated membranes agreed with that calculated, suggesting that the interfacial resistance between each membrane was negligible. When the FP concentration in the laminated membranes was determined by microdialysis, the observed concentration was similar to that calculated according to Fick's law of diffusion. When bovine serum albumin (BSA) solution was placed between the dialysis membranes to mimic the protein leaching in skin, the FP permeation profiles through the membranes showed a long lag-time without dependence on the depth of the region of the inserted BSA from the surface. However, the FP concentration-time profiles in a region between the membranes showed dependence on the region of the inserted BSA. Since the FP concentration in the region and the permeation rates at steady-state were similar to those without BSA solution, BSA could act as a capacity factor to the delayed reaching to a steady-state. The skin mimicking laminated membranes will be useful to evaluate drug permeation quantitatively and to imitate some events which can happen in inflamed tissues in skin without requiring animals.

Key words: skin absorption, microdialysis, artificial membrane, zero net flux, protein binding


(AATEX: Altern. Animal Test. EXperiment.: Alternatives to Animal Testing and EXperimentation)