POLY(ETHYLENE GLYCOL)-COATED ANTI-CARDIAC MYOSIN IMMUNOLIPOSOMES - FACTORS INFLUENCING TARGETED ACCUMULATION IN THE INFARCTED MYOCARDIUM

Biodistribution and infarct accumulation of different liposome prepara tions in rabbits with experimental myocardial infarction have been inv estigated. The influence of such parameters as liposome size, and pres ence or absence of poly(ethylene glycol) (PEG) and infarct-specific an timyosin antibody (AM) on liposome behavior in vivo was studied. All t hree variables were shown to affect liposome biodistribution, liposome size being the least significant variable. Statistical analysis of th e data obtained demonstrated that of all variables, PEG coating expres ses the strongest influence on the liposome blood clearance, significa ntly (P = 0.0001) increasing the mean level of blood radioactivity und er all circumstances. Infarct accumulation depended upon the presence of both PEG (P = 0.0013) and AM (P = 0.005). The infarct-to-normal rat io was affected by the presence of AM (P = 0.0002), but the extent of the effect depended also on the presence of PEG (P = 0.01). Two differ ing mechanisms can be seen in infarct accumulation of PEG-liposomes (s low accumulation via the impaired filtration) and AM-liposomes (specif ic binding of immunoliposomes with the exposed antigen), Both mechanis ms are supplementary in case of liposomes carrying PEG and AM at the s ame time, An optimization strategy is suggested for using liposomes as carriers for diagnostic (a high target-to-nontarget ratio is required ) and therapeutic (a high absolute accumulation in the target is requi red) agents.