Organ-Specific Targeting of Synthetic and Natural Drug Carriers

In the past few years, many attempts have been directed toward targeting intravenously injected colloidal and cellular carriers (including liposomes, lipoproteins and microspheres, and lymphocytes) selectively to various macrophages, hepatocytes, bone marrow endothelium, pulmonary endothelium, liver endothelial cells, and to the sites of transplanted tumors in various animal models. These studies are based on two principles: opsonization and receptor-mediated targeting. This chapter concentrates on the intravenous route of administration to illustrate opportunities and challenges in targeting colloidal carriers within and outside the vascular compartment. Organ- and cellular-specific targeting can also be achieved with lipoproteins. Some organs tend to accumulate specific classes of lipoproteins. For example, in rabbits and marmosets, bone marrow is a major site of lipoprotein uptake. Uptake in marrow occurs by perisinusoidal macrophages and is restricted to triglyceride-rich lipoproteins (chylomicrons, chylomicron remnants, and VLDL, but not β-VLDL or apoE-HDL). Hepatic uptake of lipoproteins is not as specific as the bone marrow because it has the ability to remove a variety of both triglyceriderich and cholesterol-rich lipoproteins. Addition of apoE to remnant chylomicrons results in an increase in clearance rate by the liver and not by the bone marrow. In contrast to rabbits and marmosets, chylomicron clearance by the bone marrow of rats, guinea pigs, and dogs is much less and the spleen removes a large fraction of chylomicrons.