Differential uptake of chloroquine by human keratinocytes and melanocytes in culture

The antimalarial drug chloroquine has a high affinity for melanin and accumulates in melanin-rich compartments such as those of the eye. Chloroquine is also deposited in cutaneous tissue, but whether the drug distribution is restricted to melanin-producing cells of the skin is not known. In the present study, the uptake of chloroquine by normal human epidermal keratinocytes was compared with that by melanocytes. Selectively cultivated cells were incubated at drug concentrations ranging between 0 and 10000 ng/ml for periods of up to 48 h. Chloroquine was quantified in cells and medium using high performance liquid chromatography and fluorometric detection. In both types of cells there was a rapid uptake of chloroquine within the first 2 h, followed by a slower uptake for 2-6 h until a steady-state condition was reached. Dose dependency was linear, with no sign of saturation, and approximately ten times higher drug concentrations were attained in melanocytes as compared with keratinocytes. No formation of desethylchloroquine, the major systemic metabolite, was detected in either cell type. The observed affinity of chloroquine for normal epidermal melanocytes in vitro suggests that the density and melanogenic activity of skin pigment cells may influence the cutaneous drug disposition of chloroquine.