Passive and semi-active targeting of bone marrow and leukemia cells using anionic low cholesterol liposomes

Historically, the use of liposomes to enhance delivery of anticancer agents to cancer cells has focused primarily on solid tumors, which are characterized by rapid angiogenesis resulting in a poorly formed hypervasculature with abnormal vessel walls. The leaky vasculature in combination with poor lymphatic drainage has been demonstrated to lead to the accumulation of liposomes via the enhanced permeation and retention effect. However, only very limited information exists on the disposition of such delivery systems in the bone marrow compartment, the primary site of tumor cell origination and growth for many hematological malignancies. In this review we discuss the biological properties of anionic low-cholesterol liposome formulations and their potential for passively accumulating within the bone marrow and being selectively engulfed by leukemia cells compared to normal bone marrow cells. The therapeutic implications for preferential bone marrow delivery as well as the potential routes for the internalization of drug-encapsulated liposomes into cells in the absence of a targeting ligand are reviewed.