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Targeted accumulation of polyethylene glycol‐coated immunoliposomes in infarcted rabbit myocardium
Author(s) -
Torchilin V. P.,
Klibanov A. L.,
Huang L.,
O'Donnell S.,
Nossiff N. D.,
Khaw B. A.
Publication year - 1992
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.6.9.1612296
Subject(s) - liposome , polyethylene glycol , peg ratio , in vivo , monoclonal antibody , drug carrier , chemistry , microbiology and biotechnology , pharmacology , medicine , antibody , biochemistry , immunology , drug , biology , finance , economics
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, 111 In‐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.; Klibanov, A. L.; Huang, L.; O'Donnell, S.; Nossiff, N. D.; Khaw, B. A. Targeted accumulation of polyethylene glycolcoated immunoliposomes in infarcted rabbit myocardium. FASEB J. 6: 2716‐2719; 1992.