Study of a Drug Interaction Involving the Permeation Process Using an Artificial Skin Model as an Alternative to Animal Skin

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

Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan

AATEX 15(2):97-105, 2010

A skin-mimicking model membrane system consisting of a silicone membrane and laminated dialysis membranes as a skin model based on artificial membranes was prepared and used to study a drug interaction involving protein binding. Bovine serum albumin (BSA) solution was placed between the dialysis membranes to mimic the protein leaching in inflamed skin and flurbiprofen (FP), selected as a model drug, was applied to the surface of the laminated membranes. A linear relationship between the FP permeation rate through and the FP concentration in the laminated membranes suggested that the unbound FP concentration in each region can be calculated from the permeation rate in the membrane system. The FP concentration in the laminated membranes decreased depending on the concentration of BSA placed in the membranes. When ketoprofen (KP) was introduced into the microdialysis probe to inhibit the BSA binding of FP during the permeation process, the FP permeation through the laminated membranes and the free concentration in BSA solution in the laminated membranes were increased. This result was due to a competitive interaction of FP and KP involving protein binding. Such simultaneous permeation-binding of two drugs is difficult to study in vivo and in vitro. Our experimental system will help researchers to understand such complicated process and, therefore, reduce the use of experimental animals in the development of new skin products.

key words: skin absorption, drug interaction, artificial membrane, skin model, protein binding


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