Targeted Liposomal Drug Delivery to Monocytes andMacrophages

As the role of monocytes and macrophages in a range of diseases including infectious disease, inflammatory diseases, cancer, and atherosclerosis is better understood, strategies to target these cell types are of growing importance both scientifically and therapeutically. As particulate carriers, liposomes naturally target cells of the mononuclear phagocytic system (MPS), particularly macrophages. Loading drugs into liposomes can therefore offer an efficient means of drug targeting to MPS cells. Physicochemical properties including size, charge, and lipid composition can have a very significant effect on the efficiency with which liposomes target MPS cells. Small, negatively charged liposomes appear to target macrophages most efficiently by interaction with scavenger receptors on the macrophage cell surface. MPS cells express a range of receptors including scavenger receptors, integrins, mannose receptors, and Fc-receptors that can be targeted by the addition of ligands to liposome surfaces. These ligands include peptides, antibodies, and lectins and have the advantages of increasing target specificity and avoiding the need for cationic lipids to trigger intracellular delivery. The goal for targeting monocytes/macrophages using liposomes includes not only drug delivery but also potentially a role in cell ablation and cell activation for the treatment of conditions including cancer, atherosclerosis, HIV, and chronic inflammation.