A novel system to study the impact of epithelial barriers on cellular metabolism

Medications introduced into the systematic circulation must be transported across biological barriers such as skin, gastrointestinal, or bronchial epi thelia, which can alter their kinetic and metabolic profiles. It is, theref ore, important to understand diffusion kinetics across barrier membranes wh en choosing a dosing regime that will elicit the greatest cellular response . An in vitro system that combines membrane transport studies with a downst ream cell culture chamber has been developed. The system has been tested wi th skin and a small intestine model (Caco-2 cell monolayers) as barriers, t he peroxovanadium compound [VO(O-2)(2) 1, 10 phenanthroline] bpV(phen), as the test chemical, Hep-G2 (liver) as the test cells, and glucose consumptio n as the test assay. Peroxovanadium has insulin mimetic properties and has been previously demonstrated to effectively lower blood glucose levels in d iabetic rats when administered transdermally. A dose of 10 mM bpV(phen) pla ced on the skin epidermis with a continuous iontophoretic current of 0.5 mA /cm(2) for 4.5 h led to a net 22% increase in glucose consumption by Hep-G2 cells. The same dose of bpV(phen) passively diffusing across a Caco-2 cell monolayer led to an increase in glucose consumption by Hep-G2 cells of 23% . This system is highly versatile and can be used to study many other proce sses, involving a variety of biological membranes, cell types, chemicals an d assays, making it a valuable research tool. (C) 2000 Biomedical Engineeri ng Society. [S0090-6964(00)00710-4].