Intranasal mucoadhesive microemulsion of tacrine to improve brain targeting
Intranasal mucoadhesive microemulsion of tacrine to improve brain targeting
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DOI：
10.1097/wad.0b013e318157205b
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发表时间：
2008-04-01
影响因子：
2.1
通讯作者：
Misra, Ambikanandan R.
中科院分区：
文献类型：
--
作者：
Jogani, Viral V.;Shah, Pranav J.;Misra, Ambikanandan R.
本研究的目的是制备和表征他克林微乳/粘附性微乳(TME/TMME)，评价其对脑靶向和改善记忆障碍小鼠的药代动力学和药效学性能。采用滴定法制备了TME并对其进行了表征。以~(99m)Tc为标志物，评价他克林溶液和制剂在静脉和鼻腔给药后的生物分布。根据这些数据，计算了药物动力学参数、药物靶向效率和直接经鼻到脑的药物转运。为了确定药物在兔脑内的定位，进行了伽玛核素扫描。鼻腔给药的T-max值(60min)低于静脉给药(120min)，提示有选择性的鼻-脑转运。TMME鼻腔给药后他克林的脑生物利用度比他克林鼻腔溶液高2倍，说明TMME鼻腔给药后药物在脑内的分布范围更大。兔脑核素扫描也显示，鼻腔给药后，药物进入大脑的摄取率更高。结果表明，TMME鼻腔给药后，他克林进入小鼠脑内的速度快，进入小鼠脑内的范围更大，记忆丧失的恢复最快。因此，结果提示他克林鼻腔给药在治疗阿尔茨海默病患者中可能起到作用。
The aim of the investigation was to prepare and characterize microemulsion/mucoadhesive microemulsion of tacrine (TME/TMME), assess its pharmacokinetic and pharmacodynamic performances for brain targeting and for improvement in memory in scopolamine-induced amnesic mice. The TME was prepared by the titration method and characterized. Biodistribution of tacrine solution and formulations after intravenous and intranasal administrations were evaluated using Tc-99m as marker. From the data, the pharmacokinetic parameters, drug targeting efficiency, and direct nose-to-brain drug transport were calculated. To confirm drug localization in brain gamma scintigraphy in rabbits was performed. Lower T-max values (60 min) after intranasal compared with intravenous administration (120 min) suggested selective nose-to-brain transport. The brain bioavailability of tacrine after intranasal TMME compared with intranasal tacrine solution was found to be 2-fold higher indicating larger extent of distribution of the drug to brain with intranasal TMME. Rabbit brain scintigraphy also showed higher uptake of drug into the brain after intranasal administration. The results demonstrated rapid and larger extent of transport of tacrine into the mice brain and fastest regain of memory loss in scopolamine-induced amnesic mice after intranasal TMME. Hence, results are suggestive of possible role of intranasal tacrine delivery in treating Alzheimer's patients.