Delivery Of ～(125)Ⅰ-cobrotoxin After Intranasal Administration To The Brain: A Microdialysis Study In Freely-moving Rats

In order to determine the contribution of intranasal (i.n.) administration to the uptake of large molecular weight (MW) substances into central nervous system (CNS), concentration in brain of the centrally acting polypeptide cobrotoxin (NT- I ) versus time profiles, radiolabeled with sodium 1251-Iodide, were studied using dual-probe microdialysis in awake free-moving rats. ¹²⁵I- NT- I was administered at the same dose of 105 μ g/kg intravenously and intranasally, with borneol, menthol, borneol/menthol eutectic mixture ( + BMEM) and borneol/ salicylic acid eutectic mixture ( + BSEM) as absorption enhancers, respectively, and without, in the same set of rat (n=24). After application, the dialysates sampled simultaneously from right olfactory bulb and cerebellar nuclei were measured in a gamma-counter for radioactivity, and the concentration of NT- I was recalculated by in vivo recovery of microdialysis probes. The results showed that the area under the curve (AUC) value in cerebeliar nuclei (2283.51 ±34.54 min ng/ml) following i.n. administration (+ BMEM) were significantly larger than those (AUColfactory= 1141.92 ± 26.42 min ng/ml; AUCcerebellar=1364.62 ±19.35 min ng/ml) after intravenous (i.v.) bolus. A prolonged time values to peak concentration after i.n. application (+BMEM) were observed compared with those following i.v. administration and with those from other i.n. administration group. Also, following i.n. application (+BMEM) the measured...