Liposome targeting following intravenous administration: Defining expectations and a need for improved methodology

The prospects for developing improved liposome based anti-cancer drug formulations are great, particularly when considering the potential role of lipid-based formulations for delivery of biopharmaceuticals. It is important however, to pursue improved formulations with an expectation of what the improvements are designed to achieve and an understanding of the pharmaceutical issues involved in development of such a drug. Our efforts in this area have focused on the important role of liposome extravasation in defining therapeutic activity of intravenously administered liposomal anticancer drugs. We have developed targeting strategies based on two key assumptions. First, cell specific targeting is an attribute required after the passive extravasation of a drug-loaded carrier. Accordingly, if targeting is to be of potential therapeutic value it is important that the targeting features do not Interfere with the tendency of the carrier to move from the blood compartment to an extravascular site. Second, it is critical to demonstrate that liposomes that have extravasated are available for targeting. As part of this effort we have identified a need to develop simple, pharmaceutically viable, procedures for the preparation of stable protein conjugated liposomes.