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 β-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.
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