title: Immunomicelles: targeted pharmaceutical carriers for poorly soluble drugs.
abstract: To prepare immunomicelles, new targeted carriers for poorly soluble pharmaceuticals, a procedure has been developed to chemically attach mAbs to reactive groups incorporated into the corona of polymeric micelles made of polyethylene glycol-phosphatidylethanolamine conjugates. Micelle-attached antibodies retained their ability to specifically interact with their antigens. Immunomicelles with attached antitumor mAb 2C5 effectively recognized and bound various cancer cells in vitro and showed an increased accumulation in experimental tumors in mice when compared with nontargeted micelles. Intravenous administration of tumor-specific 2C5 immunomicelles loaded with a sparingly soluble anticancer agent, taxol, into experimental mice bearing Lewis lung carcinoma resulted in an increased accumulation of taxol in the tumor compared with free taxol or taxol in nontargeted micelles and in enhanced tumor growth inhibition. This family of pharmaceutical carriers can be used for the solubilization and enhanced delivery of poorly soluble drugs to various pathological sites in the body.
authors.affiliation: Department of Pharmaceutical Sciences, Bouve College of Health Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA. v.torchilin@neu.edu
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Torchilin
authors.forename: Anatoly N
authors.initials: AN
authors.lastname: Lukyanov
authors.forename: Zhonggao
authors.initials: Z
authors.lastname: Gao
authors.forename: Brigitte
authors.initials: B
authors.lastname: Papahadjopoulos-Sternberg
mesh_terms: D000818:Animals; D000906:Antibodies; D001692:Biological Transport; D001943:Breast Neoplasms; D004337:Drug Carriers; D015195:Drug Design; D005260:Female; D005452:Fluoresceins; D005614:Freeze Fracturing; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D007700:Kinetics; D008175:Lung Neoplasms; D008223:Lymphoma; D008657:Metabolic Clearance Rate; D051379:Mice; D008823:Micelles; D008854:Microscopy, Electron; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D012995:Solubility; D014407:Tumor Cells, Cultured
chemical_list: D000906:Antibodies; D004337:Drug Carriers; D005452:Fluoresceins; D007205:Indium Radioisotopes; D008823:Micelles; D010714:Phosphatidylethanolamines; C067972:dioleoyl-N-(monomethoxypolyethylene glycol succinyl)phosphatidylethanolamine; C024098:6-carboxyfluorescein; D011092:Polyethylene Glycols