Richard Kirsh

[15] Liposome-mediated macrophage activities

Publisher Summary This chapter discusses the relevant methodology for evaluating liposome behaviour in vivo with particular emphasis on the elevation of liposome-encapsulated biological response modifier (BRM) to augment macrophage-mediated host defences against neoplastic and infectious diseases. Liposome-encapsulated antifungal drugs might reasonably be expected to have limited success in treatment of infections with the more common opportunistic fungi, where the organisms grow extracellularly. However, selective delivery of antifungal agents to macrophages may still be therapeutically useful. Phagocytic uptake of fungi by macrophages that contain drug would be expected to enhance intracellular destruction of the phagocytosed organisms. In addition, macrophages that have phagocytosed liposomes, containing drug might act as a mobile slow-release depot. For example, macrophages that endocytosed liposomes containing antifungal drugs, while in the circulation may migrate to the site of infection and release drugs locally over a prolonged period.

Stimulation of host resistance to metastatic tumors by macrophage activating agents encapsulated in liposomes.

The disappointing results obtained in experimental and clinical efforts to devise effective, specific, active immunotherapy procedures for the treatment of cancer have stimulated renewed interest in mechanisms of non-specific “natural” antitumor surveillance mediated by macrophages and natural killer cells. A significant effort is now underway in many laboratories to develop effective biological response modifier (BRM) agents that can stimulate the antitumor activities of these cells. Liposomes offer a useful carrier system for delivering BRM agents to macrophages in vivo. When injected i.v. the majority of liposomes are taken up by phagocytic reticuloendothelial cells in the liver and spleen, and by circulating monocytes (reviewed in 6). The passive localization of liposomes into mononuclear phagocytes is frustrating to investigators who wish to target liposomes to other cell types in the body, including tumor cells, but provides a highly effective mechanism for “targeting”, albeit passively, of liposome-encapsul-ated materials to macrophages. We have exploited this pathway to deliver natural and synthetic molecules with macrophage activating activity to macrophages in situ.