BIODISTRIBUTION AND IMMUNOTARGETABILITY OF GANGLIOSIDE-STABILIZED DIOLEOYLPHOSPHATIDYLETHANOLAMINE LIPOSOMES

The biodistribution and immunotargetability of liposomes composed primarily of dioleoylphosphatidylethanolamine (DOPE) or dioleoylphosphatidylcholine (DOPC) in mice injected via the tail vein were examined and compared. The ganglioside G(M1) (7 mol%) prolonged the circulation of DOPC but not DOPE liposomes. Gangliosides G(D1a) and G(T1b) (7 mol%) also increased the amount of DOPC liposomes remaining in circulation, and to a similar extent as G(M1), at 15 min post injection. However, these liposomes were cleared from the circulation by 2.5 h. Monoclonal antibody 34A, which specifically binds to a surface glycoprotein (gp 112) of the pulmonary endothelial cell surface, was coupled with N-glutarylphosphatidylethanolamine and incorporated into liposomes by a dialysis procedure. These 34A-immunoliposomes, composed of DOPE and G(M1) (7 mol%), but not the antibody-free liposomes, accumulated efficiently (almost-equal-to 24% of the injected dose) in the lungs. Inclusion of cholesterol (31 mol%) enhanced the lung accumulation of both DOPE/G(M1) immunoliposomes and DOPC/G(M1) immunoliposomes to 33% and 51% of the injected dose, respectively. The transient increase in DOPC liposome circulation provided by G(D1a) and G(T1b) was sufficient to enhance DOPC immunoliposome binding, where 44% and 43% of the injected dose of DOPC/Chol/G(D1a) and DOPC/Chol/G(T1b) immunoliposomes accumulated in lung at 15 min after injection, respectively. In general, cholesterol-containing DOPC liposomes were more targetable than DOPE liposomes, and the degree to which these liposomes avoid RES uptake influences their targetability. The results presented here are relevant to the design of targetable drug delivery vehicles.