TARGETING OF TENIPOSIDE TO THE MONONUCLEAR PHAGOCYTIC SYSTEM (MPS) BYINCORPORATION IN LIPOSOMES AND SUBMICRON LIPID PARTICLES - AN AUTORADIOGRAPHIC STUDY IN MICE

Liposomes are concentrated in the mononuclear phagocytic system in viv o and may therefore be of value as carriers of drugs when treating dis eases involving phagocytic cells. Teniposide (VM-26) is a potent and l ipophilic cytotoxic drug. Teniposide was incorporated in large unilame llar liposomes (LUVs) consisting of egg phosphatidylcholine and dioleo yl phosphatidic acid and into the novel submicron lipid particles cont aining cholesteryl oleate, cholesteryl palmitate and soybean lecithin, in order to evaluate the drug targeting effect. Radiolabelled tenipos ide and lipids were used and the organ distribution in mice was studie d with whole-body autoradiography 20 and 90 min post i.v. injection, W hen the commercial formulation of teniposide (Vumon(R)) was administer ed, teniposide accumulated in the liver where the drug is metabolized. Biliary excretion was rapid and considerable already after 20 min. Th e liposomal formulation enhanced liver uptake of teniposide slightly. The distribution of radiolabelled phosphatidyl choline differed from t hat of teniposide indicating instability of the liposomes in circulati on. Despite this, the splenic uptake of the drug was significantly enh anced by administration in liposomes. In the red pulp of the spleen th e teniposide level was 23 times higher 90 min post injection, using th e liposomal formulation as compared to free drug. The submicron lipid particles were mainly accumulated in the liver and to a lesser extent in the spleen. The study shows that liposomes and lipid particles enha nce splenic and liver uptake and can be used to target teniposide to t he MPS.