ABSTRACT
Using two rat monoclonal antibodies, (34A, 201B) which specifically bind to a surface glycoprotein of the pulmonary endothelial cells, we have demonstrated that i.v. injected immunoliposomes containing these antibodies accumulate efficiently in the lung of mice. The accumulation of immunoliposomes at the target site is immunospecific because immunoliposomes, bearing nonspecific antibody or liposomes without antibody, do not accumulate at the target. Furthermore, lung accumulation of specific immunoliposomes can be completely blocked by a preinjection of excess free antibody. The level of lung accumulation increases significantly as the antibody to lipid ratio of the immunoliposomes increases. Approximately 60% of injected dose is accumulated in the lung, with an average of 935 antibody molecules per liposome. The rest of the liposomes are taken up primarily by the liver and spleen. Amphiphiles such as ganglioside GM1, which decrease the affinity of liposomes to the liver and prolong the circulation time of liposomes in the blood, enhance the binding of immunoliposomes to the lung target. However, not all amphiphiles which prolong the circulation time of liposomes can enhance the binding of immunoliposomes to the lung target. Amphiphiles, such as polyethyleneglycol-5000 which significantly increase the circulation time of liposomes, actually decrease the binding of immunoliposomes to the lung target. This is probably because the long polyethyleneglycol chains on the liposome surface present a strong steric barrier which prevents the immunoliposomes from approaching the target cells closely. Shorter polyethyleneglycol chains, with less steric barrier activity, supported the target binding of immunoliposomes in a manner similar to that of GM1. These studies offer some important insights into the potential of target-specific drug delivery by immunoliposomes.
