title: The design and evaluation of a novel targeted drug delivery system using cationic emulsion-antibody conjugates.
abstract: In an attempt to design a targeted drug delivery system to tumors' over-expressing H-ferritin specifically recognized by a monoclonal antibody, AMB8LK, a cationic emulsion - AMB8LK conjugate was prepared. A novel cross-linker molecule bearing maleimide group was synthesized and added to cationic emulsion formulation for AMB8LK Fab' fragment covalent coupling. NMR spectroscopy confirmed the cross-linker synthesis and the preservation of the active maleimide function. SDS gel-electrophoresis results corroborated the formation of the Fab' fragment. Different densities of Fab' fragments (10-200 Fab'/oil droplet) were conjugated to emulsion droplet interface and no changes in the physico-chemical properties were observed ( approximately 120 nm size and zeta potential of approximately +30 mV). The coupling efficiency ranged from 55% to 70% and was visualized by TEM showing gold particles attached to the droplet interface. Cell culture studies demonstrated specific binding to cells as confirmed by the occurrence of the marked reduction in binding when free AMB8LK Mab was incubated before adding the AMB8LK-emulsion conjugate to the cells. The coupling of AMB8LK Fab' fragment to the cationic emulsion increased the cells uptake by 50% as compared to non-conjugated respective cationic emulsion. Appropriate conditions were, thus, identified for coupling AMB8LK Fab' fragment to cationic emulsion without altering the specificity and affinity of the Mab fragment to the tumor antigen.
authors.affiliation: Pharmaceutics Department, The School of Pharmacy, The Hebrew University of Jerusalem, POB 12065, Jerusalem 91120, Israel.
authors.forename: Danny
authors.initials: D
authors.lastname: Goldstein
authors.forename: Taher
authors.initials: T
authors.lastname: Nassar
authors.forename: Gregory
authors.initials: G
authors.lastname: Lambert
authors.forename: Jean
authors.initials: J
authors.lastname: Kadouche
authors.forename: Simon
authors.initials: S
authors.lastname: Benita
mesh_terms: D000588:Amines; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry; D000912:Antibodies, Neoplasm / Q000008:administration & dosage* / Q000737:chemistry; D002412:Cations / Q000737:chemistry; D045744:Cell Line, Tumor; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003432:Cross-Linking Reagents; D016572:Cyclosporine / Q000008:administration & dosage; D016503:Drug Delivery Systems; D015195:Drug Design; D004591:Electrophoresis, Polyacrylamide Gel; D004655:Emulsions; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007700:Kinetics; D008301:Maleimides; D010316:Particle Size; D012995:Solubility
chemical_list: D000588:Amines; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D002412:Cations; D003432:Cross-Linking Reagents; D004655:Emulsions; D007140:Immunoglobulin Fab Fragments; D007166:Immunosuppressive Agents; D008301:Maleimides; C025285:N-(4-carboxycyclohexylmethyl)maleimide N-hydroxysuccinimide ester; D016572:Cyclosporine; C009317:stearylamine