Fatty acid acylated Fab‐fragments of antibodies to neurospecific proteins as carriers for neuroleptic targeted delivery in brain

FEBS Letters

Zhirkov, Yurii A.²  Kabanov, Alexander V.¹  Chekhonin, Vladimir P.²  Morozov, Georgii V.² 

[1] All-Union Research Center of Molecular Diagnostics and Therapy, Simpheropolskii blvd. 8, Moscow 113149, USSR;V.P. Serbsky All-Union Research Institute for General and Forensic Psychiatry, Kropotkinskii per. 23, Moscow 119839,USSR

关键词: Drug targeting;    Stearoylated Fab-fragment;    Reversed micelle;    Neuroleptic;    Neurospecific antibody;    Aerosol OT;    AOT;    sodium bis(2-ethylhexyl)sulfosuccinate;    GFA;    acid gliofibrillar antigen;    α2-GP;    α2-glycoprotein;    trifluoperazine;    stelazine;    10-[3-(4-methylpiperazin-1-yl)-propyl]-2-(trifluoromethyl)-10H-phenothiazinc;    TNBS;    2;    4;    6-trinitrobenzenesulfonic acid;   

DOI  :  10.1016/0014-5793(91)80037-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 α₂-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.

【 授权许可】

Unknown