[A liposomal form of diamidine: reduced toxicity]

The cultures of Nuttalia eque mainly develop in the reticuloendothelial organs and so in treatment of nuttaliosis in horses and the Nuttalia carriers diamidine, an analog of imidocarb or imidozoline, was used encapsulated in liposomes. The liposomes were prepared with a modification of the phase inversion method (the lipids were dissolved in a mixture of freon-11 and chloroform). The content of the organic solvents in the preparation, as evidenced by gas liquid chromatography, was less than 0.2 per cent. The main fraction consisted of particles 1.5 to 2.5 microns in diameter. The tests on animals of various species revealed a significant decrease in the toxicity of diamidine when used encapsulated in liposomes as compared to the use of the free diamidine. The LD50 of the liposome encapsulated diamidine administered intravenously and intramuscularly was for albino mice 52 and 6000 mg/kg, respectively whereas that of the free diamidine was 0.8 and 84 mg/kg, respectively. In a dose of 10 mg/kg administered intramuscularly the free diamidine induced death in 100 per cent of the horses while in a dose of 10 mg/kg the liposome encapsulated diamidine was satisfactorily tolerated by the animals. The liposome encapsulated diamidine had no unfavourable effect on hepatic antitoxic and metabolic functions. One should hope that the low toxicity of the liposome-encapsulated diamidine will provide its higher chemotherapeutic index.