DEVELOPMENT OF LIPOSOMAL ANTHRACYCLINES - FROM BASICS TO CLINICAL-APPLICATIONS

The pharmacokinetics of liposome-encapsulated drugs are controlled by the interplay of two variables: the rate of plasma clearance of the li posome carrier, and the stability of the liposome-drug association in the blood stream. The pharmacokinetic properties of the liposomal drug , the vesicle size of the liposome carrier and the vascular permeabili ty of individual tissues will determine the extravasation and biodistr ibution profile. The pharmacokinetics of polyethylene-glycol-(PEG)-lip osomal doxorubicin are characterized by an extremely long circulating half-life, slow plasma clearance and reduced volume of distribution co mpared to free doxorubicin. These carrier systems show an improved ext ravasation profile with enhanced localization in tumors and superior t herapeutic efficacy in comparison to doxorubicin in free form. These p roperties are the result of an optimized liposome composition and of a special drug-loading method which produces stable and long-circulatin g carriers. In clinical studies, doxorubicin encapsulated in PEG-coate d liposomes shows a unique pharmacokinetic-toxicity profile and promis ing antitumor activity. (C) 1998 Elsevier Science B.V.