Biodistribution of clodronate and liposomes used in the liposome mediated macrophage 'suicide' approach

Clodronate (Cl(2)MBP; dichloromethylene-bisphosphonate)-containing liposomes are used to investigate the role of macrophages in immune and non-immune defense mechanisms by elimination of these macrophages followed by functional studies. The present studies characterize such liposomes in terms of the leakage of clodronate and the biodistribution of both the encapsulated drug and the liposomal carrier. The distribution of liposomes was studied using a radioactively labelled lipid phase marker (In-111-DTPA-SA) and the distribution of the encapsulated drug was examined following injection of radioactively labelled clodronate (Tc-99m-Cl(2)MBP). Furthermore, the biodistribution of variously composed multilamellar liposomes (EPC/Chol molar ratio 7:1.3 or 7:7; EPC/Chol/PS 7:1.3:1 or 7:7:1; EPC/Chol/M 7:2:1; EPC/Chol/MPE 7:2:1) after intravenous injection was investigated. The findings suggest that only one third of the originally entrapped clodronate was still encapsulated in the liposomes at the time of ingestion by the macrophages in the liver and spleen after intravenous injection of the clodronate containing liposomes. 3 h after injection no clodronate could be detected in the circulation.