Enhancement of blood-brain barrier permeability by sodium caprate.
We examined the effect of sodium caprate on the integrity of the tight junctions of brain capillary endothelial cells, using a modified in-situ brain perfusion technique. Model hydrophilic compounds used were [3H]mannitol, [14C]sucrose, [3H]PEG900, [3H]PEG4000, FITC-dextran 4000, FITC-dextran 20000 and FITC-dextran 70000. The brain distribution volume of [14C]sucrose was significantly increased by sodium caprate in a concentration-dependent manner. The effective minimum concentration was 10mM. Furthermore, the effects of sodium caprate on the distribution volumes of hydrophilic compounds, [3H]mannitol, [14C]sucrose, [3H]PEG900, [3H]PEG4000, FITC-dextran 4000, FITC-dextran 20000 and FITC-dextran 70000, showed a molecular weight dependence. A plot of apparent permeation clearance against diffusion coefficient values suggested that 20 mM sodium caprate induced pores so large that the above compounds could pass through the blood-brain barrier with negligible friction within the pore. Our results showed that intracarotid sodium caprate perfusion could enhance the permeation of hydrophilic compounds through the blood-brain barrier.
Ohnishi
T
T
Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachiouji, Japan.
Aida
K
K
Awazu
S
S
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D003652:Decanoic Acids / Q000494:pharmacology*; D003911:Dextrans / Q000493:pharmacokinetics*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016014:Linear Models; D008297:Male; D008353:Mannitol / Q000493:pharmacokinetics*; D008970:Molecular Weight; D010477:Perfusion; D010539:Permeability / Q000187:drug effects; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013395:Sucrose / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D003652:Decanoic Acids; D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D008353:Mannitol; D011092:Polyethylene Glycols; C031071:decanoic acid; D013395:Sucrose; D016650:Fluorescein-5-isothiocyanate