Liposomes for specific depletion of macrophages from organs and tissues

Abstract

A liposome mediated macrophage "suicide" approach has been developed, based on the liposome mediated internalization of the small hydrophilic molecule clodronate in macrophages J Leukoc Biol 62:702, 1997. 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 and specificity 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.