Encapsulation of doxorubicin in liposomes containing phosphatidylethanol. Part 2: Physicochemical characterization and antitumor activity of “solid” liposomes

Abstract

Doxorubicin has been encapsulated into "solid" liposomes composed of a mixture of distearoyl analogs of phosphatidylcholine and phosphatidylethanol (in a 3 : 2 molar ratio). The liposomes are sterically stabilized by incorporating a conjugate of dipalmitoylphosphatidylethanolamine with poly(ethylene glycol)-2000 in an amount of 5 wt % with respect to the total lipid content. The data of differential scanning microcalorimetry method show that the lipid bilayer of the doxorubicin-containing liposomes occurs in a gel-like ("solid") state up to a temperature of 47°C. Estimated in terms of inhibition of the growth of solid and ascitic Ehrlich's carcinoma in mice, the antitumor effect of such liposomes is equal to that of ordinary doxorubicin, whereas sterically non-stabilized "solid" liposomes are 1.5 times less active.