AIM: To determine the uptake extent of Huperzine A (Hup A) into the brain after intranasal administration of Hup A in situ gel to rats, and to compare the pharmacokinetic parameters between intranasal administration and iv and po. METHODS: Hup A was administered to male Sprague-Dawley rats via nasal, iv and oral routes at the dose of 166.7, 166.7, and 500 mug/kg, respectively. Blood and brain tissue samples including the cerebrum, hippocampus, cerebellum and olfactory bulb were collected, and the concentrations of Hup A in the samples were assayed by HPLC. The area under the concentration-time curve (AUC(0-->6 h)) and the ratio of the AUC(brain) to the AUC(plasma) (drug targeting efficiency, DTE) were calculated to evaluate the brain targeting efficiency of the drug via 3 administration routes. RESULTS: The AUC(0-->6 h) of the drug in the cerebrum, hippocampus, cerebellum, left olfactory bulb and right olfactory bulb after intranasal administration of the Hup A in situ gel were 1.5, 1.3, 1.0, 1.2, and 1.0 times of those after iv administration of the injection, and 2.7, 2.2, 1.9, 3.1, and 2.6 times of those after administration of the oral formulation. The AUC (brain0-->6 h)/AUC(plasma0-->6 h) of Hup A in the cerebrum, hippocampus and left olfactory bulb following the intranasal administration dose were significantly higher (P<0.05) than the iv dose. CONCLUSION: Intranasal delivery showed a viable, non-invasive strategy for delivering the drug into brain.
AIM: To determine the uptake extent of Huperzine A (Hup A) into the brain after intranasal administration of Hup A in situ gel to rats, and to compare the pharmacokinetic parameters between intranasal administration and iv and po. METHODS: Hup A was administered to male Sprague-Dawley rats via nasal, iv and oral routes at the dose of 166.7, 166.7, and 500 mug/kg, respectively. Blood and brain tissue samples including the cerebrum, hippocampus, cerebellum and olfactory bulb were collected, and the concentrations of Hup A in the samples were assayed by HPLC. The area under the concentration-time curve (AUC(0-->6 h)) and the ratio of the AUC(brain) to the AUC(plasma) (drug targeting efficiency, DTE) were calculated to evaluate the brain targeting efficiency of the drug via 3 administration routes. RESULTS: The AUC(0-->6 h) of the drug in the cerebrum, hippocampus, cerebellum, left olfactory bulb and right olfactory bulb after intranasal administration of the Hup A in situ gel were 1.5, 1.3, 1.0, 1.2, and 1.0 times of those after iv administration of the injection, and 2.7, 2.2, 1.9, 3.1, and 2.6 times of those after administration of the oral formulation. The AUC (brain0-->6 h)/AUC(plasma0-->6 h) of Hup A in the cerebrum, hippocampus and left olfactory bulb following the intranasal administration dose were significantly higher (P<0.05) than the iv dose. CONCLUSION: Intranasal delivery showed a viable, non-invasive strategy for delivering the drug into brain.
Authors: Jun Chen; Hongna Pan; Cynthia Chen; Wei Wu; Kevin Iskandar; Jeffrey He; Tetsade Piermartiri; David M Jacobowitz; Qian-Sheng Yu; John H McDonough; Nigel H Greig; Ann M Marini Journal: PLoS One Date: 2014-06-23 Impact factor: 3.240