N-三甲基壳聚糖及羧甲基壳聚糖对苯甲酸利扎曲普坦鼻腔给药脑靶向性促进作用的比较研究

Comparison of the Absorption Enhancement of N-Trimethyl Chitosan and Carboxymethyl Chitosan for Rizatriptan Benzoate Nasal Administration

目的:对季胺化程度为60%的N-三甲基壳聚糖(TMC60)及羧甲基壳聚糖(CMCS)作为鼻腔给药系统吸收促进剂对苯甲酸利扎曲普坦(RB)脑靶向性促进作用进行比较。方法:SD大鼠随机分为4组其中3组分别给予同剂量的RB滴鼻剂、RB-TMC60滴鼻剂、RB-CMCS滴鼻剂第4组静脉给予同剂量的RB注射液。在预定时间点对大鼠血浆及脑组织中RB浓度进行检测,采用DAS2.0软件处理得到药动学参数,并用经鼻给药脑靶向效率(DTE)及脑靶向潜力(DTP)评价脑靶向性。结果:与RB滴鼻剂相比,TMC60及CMCS均可显著增加RB经鼻吸收入脑的药量(P<0.05),且TMC60显著提高RB在血中的药量(P<0.05);与静脉给药相比,RB滴鼻剂、RB-TMC60滴鼻剂、RB-CMCS滴鼻剂的DTE%分别为160%210%,182%,DTP%分别为37%,52%,45%,说明3种RB滴鼻剂均有一定增加脑靶向性的作用,且TMC60的脑靶向促进作用最佳(P<0.05)。结论:与CMCS相比,TMC60对RB鼻腔给药脑靶向促进作用更加显著。

Objective:To compare the brain targeting enhancement of N-trimethyl chitosan with quaternization degree of 60%(TMC60)and carboxymethyl chitosan(CMCS)used as the absorption enhancers for rizatriptan benzoate(RB)nasal administration.Methods:SD rats were randomly divided into four groups,the former three groups were respectively given RB nasal drops,RB-TMC60 nasal drops and RB-CMCS nasal drops,and the forth 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.The data were analyzed by DAS2.0 software,and the drug targeting efficiency(DTE)and the drug targeting potential(DTP)were used to evaluate the brain targeting.Results:Compared with RB nasal drop,TMC60 and CMCS both could significantly enhance RB brain absorption through nose(P<0.05),and TMC60 could notably increase RB plasma concentration as well(P<0.05).Compared with intravenous injection,DTE%of RB nasal drop,RB-TMC nasal drop and RB-CMCS nasal drop was 160%,210%and 182%,and DTP%was 37%,52%and 45%,respectively,suggesting the three RB nasal drops all could enhance brain targeting ability,and among them,the brain targeting enhancement of TMC60 was the best(P<0.05).Conclusion:Compared with CMCS,TMC60 shows better brain targeting enhancement for RB nasal administration.