Lipo¬somes as drug carriers to liver macro¬phages: fundamental and therapeutic as-pects

It is well established that after intravenous injection large-size liposomes are rapidly cleared from the blood and taken up by cells belonging to the reticulo-endothelial system (RES). Particularly, fixed macrophages in liver (Kupffer cells) and spleen are actively involved in the uptake of the vesicles.1–5 Uptake occurs by way of endocytosis followed by intralysosomal degradation of liposomal lipids and release of entrapped substances.5 The natural affinity of liposomes for macrophages has been exploited in the application of liposomes as a drug delivery system to this cell type. For example, liposomes have been used as carriers of antimicrobial agents in the treatment of intracellular infections such as experiental leishmaniasis,6 candidiasis7,8 or listeriosis.9 In these infections the microorganisms are lodged in the lysosomes of tissue macrophages, precisely the site where the liposomes end up after intravenous injection. Thus, encapsulation of relevant antibiotic drugs within liposomes results in an increased therapeutic index of these drugs when administered intravenously.