苯甲酸利扎曲普坦鼻用温度-离子敏感型原位凝胶脑靶向性研究

Brain Targeting Ability of Thermo-ion Sensitive In-situ Gels of Rizatriptan Benzoate for Intranasal Administration

目的:对苯甲酸利扎曲普坦(RB)鼻用温度-离子敏感型原位凝胶的脑靶向性进行研究。方法:SD大鼠随机分为3组,其中两组分别给予同剂量的RB滴鼻剂、RB鼻用温度-离子敏感型原位凝胶,第3组静脉给予同剂量的RB注射液。在预定时间点测定各组大鼠血浆中及脑组织中RB浓度,绘制药时曲线,采用DAS2.0软件处理得到主要药动学参数,并用脑靶向性指数(BTI)评价两种RB鼻用制剂的脑靶向性。结果:RB滴鼻剂的BTI为1.71,RB鼻用温度-离子敏感型原位凝胶的BTI为2.12,均显示有一定的脑靶向性,且原位凝胶的脑靶向性更为显著,同时原位凝胶的达峰时间及半衰期均延长,显示明显的缓释性及长效性。结论:RB鼻用温度-离子敏感型原位凝胶具有较好的脑组织靶向性。

Objective: To explore the brain targeting of rizatriptan benzoate(RB) nasal temperature-ionic sensitive in-situ gel.Methods: SD rats were randomly divided into three groups.Among them,two groups were respectively given RB nasal drops and RB nasal temperature-ionic sensitive in-situ gel,and the third group was treated with RB injection via femoral vein with the same dosage.The RB concentrations in plasma and brain of rats were determined at the predetermined time points,and the drug concentration-time curves were drawn.The data were analyzed by DAS 2.0 software,and brain targeting index(BTI) was used to evaluate the brain targeting of the two RB nasal preparations.Results: BTI of RB nasal drops was 1.71,and that of RB nasal temperature-ionic sensitive in-situ gel was 2.12.The two RB nasal preparations both showed brain targeting ability,and that of in-situ gel was more obvious.Meanwhile,tmaxand t1/2 of the in-situ gel were both prolonged,suggesting its sustained and prolonged drug release properties.Conclusion: RB nasal temperature-ionic sensitive in-situ gel exhibits promising brain targeting ability.