Comparative investigations on the uptake of basic substances into the human keratinocyte cell line HaCaT--a model for the uptake of xenobiotics into the keratinocytes of the hair follicle

The human cell line HaCaT was used to study drug uptake by keratinocytes as an in-vitro model to elucidate drug incorporation into anagen hair follicle. The basic drugs under investigation were taken up very rapidly resulting in a concentration plateau in the keratinocytes which was dependent on the drug concentration in the cell culture medium. The results obtained for HaCaT clearly demonstrated the existence of a partition-equilibrium between the extracellular and intracellular drug concentrations. Only small amounts of the offered drugs were taken up and remarkable differences were observed showing a decreasing uptake for imipramine > haloperidol > cocaine/benzoylecgonine. Total protein content in the culture medium was 3.5 +/- 0.3 mg/mL and the protein binding of the drugs to the foetal serum proteins was found to be negligible in the experiments. Overall, the in vitro findings were consistent with previous observations for in vivo drug incorporation into hair. In particular, an explanation was found for the correlation between the AUC-value and hair concentration observed in animal studies as well as for the generally low drug concentrations in non-pigmented hair.