Targeting of Teniposide to the Mononuclear Phagocytic System (MPS) by Incorporation in Liposomes and Submicron Lipid Particles; An Autoradiographic Study in Mice

Abstract

Liposomes are concentrated in the mononuclear phagocytic system in vivo and may therefore be of value as carriers of drugs when treating diseases involving phagocytic cells. Teniposide (VM-26) is a potent and lipophilic cytotoxic drug. Teniposide was incorporated in large unilamellar liposomes (LUVs) consisting of egg phosphatidylcholine and dioleoyl phosphatidic acid and into the novel submicron lipid particles containing cholesteryl oleate, cholesteryl palmitate and soybean lecithin, in order to evaluate the drug targeting effect. Radiolabelled teniposide and lipids were used and the organ distribution in mice was studied with whole-body autoradiography 20 and 90 min post i.v. injection. When the commercial formulation of teniposide (Vumon) was administered, teniposide accumulated in the liver where the drug is metabolized. Biliary excretion was rapid and considerable already after 20 min. The liposomal formulation enhanced liver uptake of teniposide slightly. The distribution of radiolabelled phosphatidyl choline differed from that of teniposide indicating instability of the liposomes in circulation. Despite this, the splenic uptake of the drug was significantly enhanced by administration in liposomes. In the red pulp of the spleen the teniposide level was 23 times higher 90 min post injection, using the 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 enhance splenic and liver uptake and can be used to target teniposide to the MPS.

Key Words:

• Teniposide
• liposomes
• lipid particles
• drug targeting
• mononuclear phagocytic system
• autoradiography