Targeted accumulation of polyethylene glycol-coated immunoliposomes in infarcted rabbit myocardium.
The less than optimal accumulation of immunoliposome-associated reagents at target sites has often been attributed to the rapid in vivo clearance of immunoliposomes from the blood. In an attempt to overcome the drawback of rapid clearance and use the targeting potential of immunoliposomes, we have prepared long-circulating, 111In-labeled immunoliposomes. Targeting properties and enhanced circulation times were demonstrated in a rabbit model of acute experimental myocardial infarct. The specificity of liposomes for newly exposed intracellular cardiac myosin at the necrotic sites was achieved by incorporating monoclonal antimyosin antibody. Extended circulation times were achieved by cocoating the antimyosin-liposomes with polyethylene glycol (PEG). The half-life of the immunoliposomes was 40 min, which increased to 200 min with 4% mol PEG and to approximately 1000 min with 10% mol PEG. The degree of binding of modified immunoliposomes at the target sites was also dependent on the concentration of PEG incorporated at the liposome surface. This study demonstrates the accumulation of long-circulating targeted liposomes at the area of acute rabbit experimental myocardial infarction.
Torchilin
V P
VP
Department of Nuclear Medicine, Massachusetts General Hospital, East, Charlestown 02129.
Klibanov
A L
AL
Huang
L
L
O'Donnell
S
S
Nossiff
N D
ND
Khaw
B A
BA
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D004337:Drug Carriers / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D005069:Evaluation Studies as Topic; D007275:Injections, Intravenous; D008081:Liposomes / Q000493:pharmacokinetics; D008657:Metabolic Clearance Rate; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000276:immunology; D009218:Myosins / Q000276:immunology*; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011817:Rabbits
D000906:Antibodies; D004337:Drug Carriers; D008081:Liposomes; D011092:Polyethylene Glycols; D009218:Myosins