A Fickian diffusion transport process with features of transport catalysis. Doxorubicin transport in human red blood cells.

Abstract

The transport of the antineoplastic drug doxorubicin (Adriamycin) in human red blood cells was investigated by measuring the net efflux from loaded cells. Previous data indicated that doxorubicin transport was a Fickian diffusion transport process of the electrically neutral molecule through the lipid domain of the cell membrane. Doxorubicin transport showed saturation kinetics and a concentration-dependent temperature dependence with nonlinear Arrhenius plots. The 2 phenomena were related to the doxorubicin partition coefficient between 1-octanol and a water phase. This relationship indicated that the 2 phenomena were caused by changes in the physicochemical proterties of doxorubicin in the aqueous phase and not by interaction of doxorubicin with cell membrane components. The physicochemical properties of doxorubicin varied with concentration and temperature because of the ability of doxorubicin to form polymers by self-association in aqueous solution like other planar aromatic molecules through pi-electron orbital interaction. Doxorubicin transport across cell membranes may take place by simple Fickian diffusion.