Liposomes for targeting of antigens and drugs: immunoadjuvant activity and liposome-mediated depletion of macrophages.
Liposomes have proven their use as a tool in various immunological studies. In our own studies, both their application as antigen carriers and as drug carriers appeared to be useful. Immune responses were elicited against free soluble protein antigens and against the same antigens in a liposome-associated (particulate) form, in order to compare both types of response. Since we were especially interested in the role of splenic macrophages in both types of response, we developed a liposome-mediated macrophage suicide approach, based on the liposome-mediated internalization of the small hydrophilic molecule clodronate in macrophages. This molecule has a very short half life when released in the circulation, but does not easily cross phospholipid bilayers of liposomes or cell membranes. As a consequence, once ingested by a macrophage in a liposome-encapsulated form, it will be accumulated within the cell as soon as the liposomes are digested with the help of its lysosomal phospholipases. At a certain intracellular clodronate concentration, the macrophage is eliminated by apoptosis. Given the fact that neither the liposomal phospholipids chosen nor clodronate are toxic to other (non-phagocytic) cells, this method has proven its efficacy for depletion of macrophage subsets in various organs. In several cases, organ-specific depletion can be obtained by choosing the right administration route for the clodronate liposomes.
van Rooijen
Nico
N
Department of Molecular Cell Biology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. nvanrooijen@ClodronateLiposomes.org
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000941:Antigens / Q000276:immunology*; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology; D016503:Drug Delivery Systems; D008081:Liposomes; D008264:Macrophages / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000941:Antigens; D008081:Liposomes; D004002:Clodronic Acid