Tissue Specific Serum Opsonins and Phagocytosis of Liposomes

Abstract

Blood clearance of intravenously injected colloidal particles such as drug carriers, liposomes, nanoparticles, microspheres etc. occurs mainly in the liver, spleen and bone-marrow by phagocytes lining blood sinuses and of these sites hepatic clearance by Kupffer cells predominates. The natural homing of drug-carriers such as liposomes to elements of the reticuloendothelial system (RES) provides the advantage of specific targeting of drugs and inmunomodulators to macrophages (Alving, 1982; Poste et al, 1979). However, it limits the prospect of delivery of drugs to cells other than phagocytic cells of liver, spleen and bone-marrow and thus the RES proves to be a major obstacle in the targeting of liposomes to other cell types and tissues. Attempts to divert liposomes away from the RES have been made by ‘blockading’ the phagocytic uptake mechanisms by pretreating animals with substances such as carbon particles or dextran sulphate (Souhami et al, 1981; Preise et al, 1981) or by saturating macrophages by predosing animals with empty liposomes followed by the ‘test’ liposomes (Abra et al, 1980; Dave and Patel, 1986). These manipulations have limited benefits in prolonging circulating half-life and alteration of tissue distribution, particularly among the RES organs. The half-life of liposomes in the circulation can also be prolonged by altering the lipid composition of liposomes (Gregoriadis and Senior, 1980; Senior and Gregoriadis, 1982; Gabizon and Papahadjopoulos, 1988; Allen et al, 1989). For example, liposomes containing cholesterol and prepared from sphingomyelin or saturated phospholipids such as dimyristoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine or distearoyl phosphatidylcholine have an extremely long half-life in the circulation (Gregoriadis and Senior, 1980; Senior and Gregoriadis, 1982). Similarly, inclusion of certain gangliosides or phosphatidylinositol which gives the liposomal surface a negative charge and increased hydrophilicity prolong the circulating half-life of liposomes with a concomitant decrease in liver and spleen uptake (Gabizon and Papahadjopoulos, 1988; Allen et al, 1989).