Liposomal cancer chemotherapy: current clinical applications and future prospects

Liposomes were discovered in 1965 [1] and their potential as vehicles for the delivery of cytotoxic drugs to rumours was rapidly appreciated [2-4]. Liposome-encapsulated cytotoxic drugs have a number of potential advantages over the corresponding unencapsulated agents (reviewed in [5]). The liposome prolongs the half-life of the drug in the circulation and alters its biodistribution pattern such that: drug deposition is increased in tumour tissue and decreased in certain dose-limiting normal tissues. In effect, a drug that is stably encapsulated within a liposomal matrix displays the pharmacokinetic profile of the liposome rather than that of the parental unencapsulated agent. This has been seen as a means of achieving a significant increase 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. Localisation of liposomes to rumours relies on their prolonged residence in the circulation in order to increase the number of passes made through the tumour'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 extravasation and retention of liposomes within the tumour interstitium Since the original description of liposomes, there has been a rather protracted period of preclinical development thar has yielded a number of liposomal preparation that are now entering clinical trials. In the interests of brevity and clarity, the extensive literature dealing with that period of definition and optimisation of liposome formulations will not be considered in detail here since it has been described elsewhere [5] Instead, this review 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 liposome research is likely to have an impact on clinical practice in the future.