A novel diffusion cell model for the in vitro assessment of transcutaneous breast cancer therapeutics: Effect of permeants on MCF-7 cells cultured within the receptor compartment

A novel model is described for investigating the potential efficacy of topically delivered anti-breast cancer agents. Using all-glass Franz diffusion cells, the permeation of 4-hydroxytamoxifen, two EGFR inhibitors (PD98059 and LY294002) and eicosapentaenoic acid (EPA) were determined from a fish oil vehicle across Cyclopore track etched membrane (CTEM) alone, full-thickness porcine ear skin alone and CTEM plus full-thickness porcine ear skin. Finally, the effect of the simultaneous permeation of these compounds was determined on the breast cancer cell line, MCF-7, cultured directly into the diffusion cell receptor compartments. The CTEM was found to be not rate limiting, and all compounds permeated the skin, with a large excess of EPA. The applied combined dose reduced the growth of MCF-7 cells by 66% after 7 days. The following conclusions were obtained: (1) MCF-7 breast cancer cells can be successfully cultured within glass Franz diffusion cells. (2) A composite diffusion cell/cell culture model can indicate the potential efficacy of topically delivered anti-breast cancer therapeutic agents. (3) The levels of LY294002, PD98059, 4-hydroxytamoxifen and EPA delivered across full-thickness skin have a major inhibitory effect on the growth of MCF-7 breast cancer cells.