title: Fatty acid acylated Fab-fragments of antibodies to neurospecific proteins as carriers for neuroleptic targeted delivery in brain.
abstract: A method for targeted delivery of neuroleptics from blood in brain based on using Fab-fragments of antibodies to antigens of brain glia cells (acid gliofibrillar antigen and alpha 2-glycoprotein) is suggested. The essence of the technique is that the molecule of neuroleptic (trifluoperazine) is conjugated with Fab-fragments of these antibodies. The conjugate thus obtained is modified by stearoylchloride in the system of Aerosol OT reversed micelles in octane. The study of the distribution of 125I-labelled conjugates in the rat organism after intracordial introduction is performed. On the contrary to the nonmodified conjugates and conjugate, containing fatty acylated Fab-fragments of antibodies, nonspecific to the rat brain, the conjugate of trifluoperazine with stearoylated Fab-fragments of antibodies to neurospecific antigens accumulate in brain tissues. The drastic increase of the neuroleptic activity of trifluoperazine resulting from its coupling with stearoylated Fab-fragments of antiglial antibodies is observed.
authors.affiliation: V.P. Sebsky All-Union Research Institute for General and Forensic Psychiatry, Moscow, USSR.
authors.forename: V P
authors.initials: VP
authors.lastname: Chekhonin
authors.forename: A V
authors.initials: AV
authors.lastname: Kabanov
authors.forename: Y A
authors.initials: YA
authors.lastname: Zhirkov
authors.forename: G V
authors.initials: GV
authors.lastname: Morozov
mesh_terms: D000215:Acylation; D000510:Alpha-Globulins / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000276:immunology; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D004337:Drug Carriers; D005227:Fatty Acids; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D009419:Nerve Tissue Proteins / Q000276:immunology*; D009457:Neuroglia / Q000276:immunology; D051381:Rats; D014018:Tissue Distribution; D014268:Trifluoperazine / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000510:Alpha-Globulins; D000941:Antigens; D004337:Drug Carriers; D005227:Fatty Acids; D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins; D007140:Immunoglobulin Fab Fragments; D009419:Nerve Tissue Proteins; D014268:Trifluoperazine