title: Uptake of fluorescein isothiocyanate-labelled dextran into the CSF after intranasal and intravenous administration to rats.
abstract: With the growing number of patients suffering from central nervous system (CNS) diseases a suitable approach for drug targeting to the brain becomes more and more important. In the present study, the contribution of the nose-CSF pathway to the uptake of the model drug fluorescein isothiocyanate-labelled dextran with a molecular weight of 3.0 kDa (FD3) into the CSF was determined in rats. FD3 was administered intranasally (489 microg/rat) and by intravenous infusion (24.4 microg/ml; 119 microg/rat) in the same set of animals (n=6). Blood samples were taken from the tail vein and CSF was sampled by cisternal puncture using a stereotaxic frame. The contribution of the olfactory pathway to the uptake of FD3 into the CSF was determined by comparing the AUCCSF/AUCplasma ratios after intranasal and after intravenous application of FD3 mimicking the blood levels after intranasal delivery. No significant difference was observed between the AUCCSF/AUCplasma ratios of FD3 after intranasal administration (1.33+/-0.40%) and intravenous infusion (1.03+/-0.56%). This indicates that in rats about 1% of the amount of FD3 in plasma reaches the CSF both after nasal and intravenous administration and that no direct transport of FD3 from the nose-CSF could be found.
authors.affiliation: Division of Pharmaceutical Technology and Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands.
authors.forename: Joke P M
authors.initials: JP
authors.lastname: in 't Veen
authors.forename: Mascha P
authors.initials: MP
authors.lastname: van den Berg
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Romeijn
authors.forename: J Coos
authors.initials: JC
authors.lastname: Verhoef
authors.forename: Frans W H M
authors.initials: FW
authors.lastname: Merkus
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D019540:Area Under Curve; D001812:Blood-Brain Barrier / Q000378:metabolism*; D003911:Dextrans / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid*; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D007262:Infusions, Intravenous; D008297:Male; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate