Tissue distribution of liposomes exhibiting long half-lives in the circulation after intravenous injection.

The previously established direct relationship between long half-life of uncharged small unilamellar liposomes in the circulation of injected animals and reduced permeability to entrapped solutes in the presence of blood plasma was investigated further. It was found that vesicle size and surface charge override state of membrane permeability in determining rates of vesicle clearance. Thus, half-lives of liposomes that were practically impermeable in plasma were much shorter for larger vesicles or vesicles with a negative charge on their surface. 111In-labelled bleomycin-containing small unilamellar liposomes with long half-lives accumulated in the liver after injection to a much lesser extent (e.g., 26%) than similar liposomes (55% of the dose) exhibiting a shorter half-life. Much of the injected long-lived liposomes (about 35%) were recovered in the carcass of the animals. Scanning of the carcasses revealed quantitative accumulation of radioactivity in the bones, presumably the phagocytic cells of the bone marrow. Long-lived liposomes appear suitable for drug delivery to, or imaging of the bone marrow.