Immunotoxicity of multiple dosing regimens of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes

Abstract

We have shown that doxorubicin entrapped in cardiolipin liposomes retain antitumour efficacy in mice but had diminished cardiac uptake and cardiotoxicity. Such liposomes are preferentially taken up by spleen. In a previous study we showed that a single dose of liposomal doxorubicin is not more toxic than free doxorubicin with regard to immunologic parameters including generation of cytotoxicity for histocompatibility alloantigens and mitogenic responsiveness. In the present study, we have explored clinically relevant multiple dosing at weekly intervals, 2, 3, or 4 times. Again, despite splenic localization of liposomal doxorubicin, the depressive effect on these immunological parameters is not greater than the effect of free drug, and, in addition, the damage is repaired earlier.