Liposome circulation time and tumor targeting: implications for cancer chemotherapy

The pharmacokinetics and biodistribution of liposome-encapsulated drugs are controlled by the interplay of two variables: the rate of plasma clearance of the liposome carrier, and the stability of the liposome-drug association in circulation. Inhibition of the rapid uptake of liposomes by the reticuloendothelial system and reduction of the rate of drug leakage have resulted in long-circulating liposomal drug systems with valuable pharmacologic properties. These carrier systems show an improved extravasation profile with enhanced localization in tumors and possibly in other tissues, such as skin. An anticancer drug, doxorubicin, encapsulated in polyethyleneglycol-coated, long-circulating liposomes, shows a unique pharmacokinetic/toxicity pattern and promising antitumor activity in initial clinical studies.