title: Conjugation of anti-My9 antibody to stealth monensin liposomes and the effect of conjugated liposomes on the cytotoxicity of immunotoxin.
abstract: The carboxylic ionophore, monensin, was successfully entrapped in stealth liposomes by employing the pH-gradient method (interior pH of liposomes 9.5; exterior pH 5.0-5.9). A maximum of 14% of monensin could be entrapped in stealth liposomes by this method. The stealth liposomes could be successfully freeze-dried having mean particle size varying between 197 and 223 nm. The stealth liposomes were conjugated to anti-My9 monoclonal antibody (targeted against CD 33 antigen) by a disulfide linkage with almost full retention of immunoreactivity. The method of conjugation of liposomes with the antibody did not alter the particle size of liposomes and resulted in only 10% leakage of monensin. In-vitro cytotoxicity studies showed that antibody-conjugated monensin liposomes (3.5x10(-8) M monensin) potentiated the cytotoxicity of anti-My9 immunotoxin by a factor of 2070, in comparison to 360-fold potentiation observed with unconjugated monensin liposomes against human HL-60 promyelocytic leukemia cells. These results indicate that it is possible to enhance the in-vitro cytotoxicity of immunotoxin by several folds using antibody-conjugated monensin liposomes.
authors.affiliation: Division of Pharmaceutics, College of Pharmacy, Florida A&M University, Tallahassee, FL 32307, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sudhan Shaik
authors.forename: N
authors.initials: N
authors.lastname: Kanikkannan
authors.forename: M
authors.initials: M
authors.lastname: Singh
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry; D004220:Disulfides; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D019084:Fluorescent Antibody Technique, Indirect; D005612:Freeze Drying; D018922:HL-60 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000922:Immunotoxins / Q000008:administration & dosage* / Q000737:chemistry; D008081:Liposomes; D008985:Monensin / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size
chemical_list: D000911:Antibodies, Monoclonal; D000935:Antifungal Agents; D004220:Disulfides; D004337:Drug Carriers; D000922:Immunotoxins; D008081:Liposomes; D008985:Monensin