title: Evaluation of brain-targeting for the nasal delivery of estradiol by the microdialysis method.
abstract: The uptake of estradiol into the cerebrospinal fluid (CSF) after intranasal and intravenous administration in rats was investigated to study whether direct nose-CSF transport of estradiol exits or not. Animals received 0.48 mg kg(-1) estradiol randomly methylated beta-cyclodextrin (RAMEB) inclusion complex intranasally and intravenously. Following nasal delivery, estradiol reached a C(max) value (mean+/-S.D.) in plasma (26.70+/-11.37 ng ml(-1)) and CSF (54.76+/-32.84 ng ml(-1)) after 20 min in each case, while after intravenous infusion, estradiol reached a C(max) value in plasma (170.08+/-64.67 ng ml(-1)) and CSF (26.48+/-11.34 ng ml(-1)) at 5 min and 60 min, respectively. The AUC(CSF)/AUC(plasma) ratio (1.60+/-0.67) after intranasal delivery differed significantly from the ratio (0.61+/-0.16) observed after intravenous infusion (P<0.05). All these results indicate that estradiol is transported into CSF via olfactory neurons, and, hence, there is a direct transport route from the nasal cavity into the CSF for estradiol.
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
authors.forename: Haibing
authors.initials: H
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Leng
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008297:Male; D017551:Microdialysis; D009296:Nasal Cavity / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004958:Estradiol