Liposome technology and the development of Myocet™ (liposomal doxorubicin citrate)

Liposomes are phospholipid membrane vesicles that can act as carriers for drugsin order to target them to specific tissues. Encapsulation within a liposome can confer benefits such as longer circulation times, higher stability and reduced toxicity due to targeting of the active drug. Important features that can alter the biodistribution or pharmacokinetics of loaded liposomes include the liposome size, lipid-to-drug ratio, surface characterization (e.g. pegylation) and the method of loading. Myocet was developed in order to target doxorubicin to tumour sites while sparing healthy tissues; in particular the heart. The Myocet loading technique involves a pH gradient and a citrate complex, which allows a very high drug-to-lipid ratioand the use of small liposomes that can accumulate in the tumour through the leaky vasculature that supplies them. Preclinical studies indicate that Myocet accumulation in tumour tissue is more persistent and pervasive than that of conventional doxorubicin. In addition, Myocet is targeted away from the heart, leading to reduced cardiotoxicity without compromising antitumour efficacy.