Encapsulation of doxorubicin in liposomes containing phospatidylethanol. Part III: Effect on the toxicity and accumulation of antibiotic in myocardium

Abstract

The toxicity of sterically stabilized doxorubicin-containing “solid” liposomes comprising a mixture of distearoyl analogs of phospatidylcholine and phosphatidylethanol (in a 3: 2 molar ratio) was evaluated. Upon infusion of the ordinary and liposomal doxorubicin in a total dose of 12 mg/kg, the early loss of mice with implanted ascitic Ehrlich’s carcinoma was 100 and 50%, respectively, and the average lifetime of the animals treated with liposomal doxorubicin was 1.6 times longer. In comparison to the ordinary doxorubicin, administration of the liposomal preparation resulted in a lower drop of the body weight (10%) and a smaller decrease in leukocyte number (12%). The results of fluorimetric measurements showed that the accumulation of antibiotic in the cardiac muscle 15–180 min after infusion of the liposomal doxorubicin was 30–57% lower than that upon infusion of the ordinary preparation.