Biodistribution of pH-sensitive immunoliposomes.

Liposomes composed of either dioleoylphosphatidylethanolamine and oleic acid (pH-sensitive) or dioleoylphosphatidylcholine and oleic acid (pH-insensitive) were injected into C3H and Balb/c mice in order to determine the tissue distribution of both the lipid and the aqueous content. The lipid component was monitored by use of [3H]cholestanyl ether and the aqueous content was monitored by use of encapsulated 125I-tyraminyl-inulin. The pH-insensitive liposomes injected into both types of mice were rapidly cleared from the blood stream followed by accumulation primarily in the liver, followed by the spleen. The presence of a monoclonal antibody on the liposome surface caused a slight acceleration in liver accumulation, though generally gave the same profile as the antibody-free liposomes. pH-sensitive liposomes were leaky upon exposure to the mouse plasma following injection. The lipid component, though, displayed a large amount (e.g., 50-70% in C3H mice) of accumulation in the lung for up to 6 h, followed by a subsequent appearance in the liver and spleen. The presence of monoclonal antibody had no effect on the tissue distribution profile. These results indicate that the pH-sensitive liposomes, although ineffective as an aqueous drug delivery agent, may be effective as a means of delivering lipophilic drugs to the lung.