Poly(ethylene glycol)-coated anti-cardiac myosin immunoliposomes: factors influencing targeted accumulation in the infarcted myocardium.
Biodistribution and infarct accumulation of different liposome preparations in rabbits with experimental myocardial infarction have been investigated. The influence of such parameters as liposome size, and presence or absence of poly(ethylene glycol) (PEG) and infarct-specific antimyosin antibody (AM) on liposome behavior in vivo was studied. All three variables were shown to affect liposome biodistribution, liposome size being the least significant variable. Statistical analysis of the data obtained demonstrated that of all variables, PEG coating expresses the strongest influence on the liposome blood clearance, significantly (P=0.0001) increasing the mean level of blood radioactivity under all circumstances. Infarct accumulation depended upon the presence of both PEG (P=0.0013) and AM (P=0.005). The infarct-to-normal ratio 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 differing mechanisms can be seen in infarct accumulation of PEG-liposomes (slow accumulation via the impaired filtration) and AM-liposomes (specific binding of immunoliposomes with the exposed antigen). Both mechanisms are supplementary in case of liposomes carrying PEG and AM at the same 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 required) agents.
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Center for Imaging and Pharmaceutical Research, Massachusetts General Hospital, Charlestown, 02129, USA.
Narula
J
J
Halpern
E
E
Khaw
B A
BA
D000818:Animals; D004337:Drug Carriers; D008081:Liposomes / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D009203:Myocardial Infarction / Q000378:metabolism*; D009218:Myosins / Q000276:immunology*; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011817:Rabbits; D014018:Tissue Distribution
D004337:Drug Carriers; D008081:Liposomes; D011092:Polyethylene Glycols; D009218:Myosins