LIPOSOME-COMPLEMENT INTERACTIONS IN RAT SERUM - IMPLICATIONS FOR LIPOSOME SURVIVAL STUDIES

Serum complement opsonizes particles such as bacteria for clearance by the reticuloendothelial system. Complement has been reported to inter act with liposomes and therefore may mediate the reticuloendothelial s ystem clearance of liposomes. This study has used a rat serum model to define some of the characteristics of liposomes which modulate their ability to activate complement. Using functional hemolytic assays and C3/C3b crossed immunoelectrophoresis, we have demonstrated that liposo mes activated rat complement in a dose-dependent manner with higher co ncentrations of liposomes activating higher levels of complement. The detection of complement activation required the inclusion of phospholi pids bearing a net charge. Complement activation occurred via the clas sical pathway; no alternative pathway activation was detected. The pre sence of cholesterol contributed to complement activation in a dose-de pendent manner. Phospholipid fatty acyl chain length did not influence complement activation while the introduction of unsaturated acyl chai ns markedly decreased levels of complement activation. Liposome size a lso influenced complement activation with 400 nm unilamellar vesicles more effectively activating complement than 50 nm vesicles for equival ent amounts of exposed lipid. These studies demonstrate that the compo sition of the liposome greatly affects the in vitro activation of rat serum complement and suggest that the biological half-life of liposome s in the circulation of rats may be altered by changing the liposome c omposition to reduce complement activation.