Liposomal cancer chemotherapy: current clinical applications and future prospects

Liposomes were discovered in 1965 [1] and their potential as vehicles for t he delivery of cytotoxic drugs to rumours was rapidly appreciated [2-4]. Li posome-encapsulated cytotoxic drugs have a number of potential advantages o ver the corresponding unencapsulated agents (reviewed in [5]). The liposome prolongs the half-life of the drug in the circulation and alters its biodi stribution pattern such that: drug deposition is increased in tumour tissue and decreased in certain dose-limiting normal tissues. In effect, a drug t hat is stably encapsulated within a liposomal matrix displays the pharmacok inetic profile of the liposome rather than that of the parental unencapsula ted agent. This has been seen as a means of achieving a significant increas e in the area under the curve in the circulation and in the tumour. Such a result mimics the effect of administering cytotoxic agents as continuous iv . infusions, without the inconvenience of the devices that are required for such delivery or the toxicity associated with systemic drug exposure. Loca lisation of liposomes to rumours relies on their prolonged residence in the circulation in order to increase the number of passes made through the tum our's vascular network. The blood vessels in a tumour are leaky as a result of structural and functional anomalies. This leakiness and the co-existing lack of a fully functional system of lymphatic drainage account for the ex travasation and retention of liposomes within the tumour interstitium Since the original description of liposomes, there has been a rather protra cted period of preclinical development thar has yielded a number of liposom al preparation that are now entering clinical trials. In the interests of b revity and clarity, the extensive literature dealing with that period of de finition and optimisation of liposome formulations will not be considered i n detail here since it has been described elsewhere [5] Instead, this revie w shall confine itself to a description of the current status of liposomal cytotoxic drugs that have entered clinical trials in patients with cancer. In addition, an attempt will be made to identify the areas in which liposom e research is likely to have an impact on clinical practice in the future.