Liposome Targeting in Animal Models: Problems and Opportunities

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Abstract
A comparison has been made of the in vivo therapeutic efficacy of free doxorubicin, and doxorubicin entrapped in non-targeted or targeted long-circulating liposomes in several animal models of cancer. Models included both human and animal solid tumours, and human hematological cancers. Treatments were given either early or late in the tumour development. Solid tumours were implanted either subcutaneously or administered intravenously in pseudometastatic models. Targeting was via whole antibodies against surface epitopes on the cancer cells. In some cases the antibodies were directed against internalizing receptors at the cell surface. A consideration of our experience to date with targeted therapy in animal models of cancer leads us to conclude that the best opportunities for ligand-mediated targeting occur when the targeted liposomal drugs have ready access to the target cell population, e.g. early in the course of the disease when the target cells are present as single cells or small groups of cells, or when the target cells are present as single cells within a readily accessible compartment such as the vasculature. Targeting to internalizing receptors appears to offer some advantages over therapy targeted to non-internalizing receptors at the cell surface.