ABSTRACT
The demonstration 17•18 early on in the 1970s that liposomes coated with cell-specific ligands (e.g., antibodies and asialoglycoproteins) can interact with and be internalized by alternative (other than macrophages) cells expressing appropriate receptors, both in vitro and in vivo, led to the concept17•18 of vesicle targeting and to novel avenues of liposome research and potential uses. Perhaps more encouraging also were indications19 that even plain liposomes could enhance the delivery of drugs to solid tumors in vivo. It was soon predicted, 18 however, that success in this area would not only require quantitative retention of entrapped drugs by vesicles (also needed for "passive" targeting to fixed macrophages) but also sufficiently long time for circulating (targeted) vesicles to encounter, and associate with, the target. Since vesicle behavior in vivo resulting from a given structural feature of the system must be closely related to the particular environment in which the system exists, knowledge of the influence of the biological milieu on both drug leakage and vesicle clearance rates appeared essential.
