摘要
目的研究盐酸阿霉素壳聚糖纳米粒(adriamycinhydrochloride chitosan nanoparticles,ADM-CS-NPs)大鼠鼻腔给药后的脑内药动学特征。方法以壳聚糖为载体材料,采用离子交联法制备ADM-CS-NPs。以清醒自由活动大鼠为实验动物模型,采用脑微透析取样技术,连续收集ADM-CS-NPs及阿霉素溶液经鼻腔给药与静脉注射给药后大鼠海马部位透析液,HPLC法测定药物浓度,分析数据计算药动学参数。结果 ADM-CS-NPs经大鼠鼻腔和尾静脉注射给药(给药剂量为1.45 mg.kg-1ADM)后,Tmax分别为(300.00±26.12)和(180.00±19.11)min,Cmax分别为(93.00±8.53)和(19.11±1.91)mg·L-1,AUC0→11h分别为(17809.05±650.24)和(5159.97±120.59)mg·h·L-1,MRT分别为(390.49±6.87)和(281.53±4.99)min;ADM-Sol经大鼠鼻腔和尾静脉注射给药后,Tmax分别为(20.00±2.91)和(20.00±2.00)min,Cmax分别为(90.00±7.31)和(10.70±0.96)mg·L-1,AUC0→11h分别为(4736.70±53.40)和(312.68±4.99)mg·h·L-1,MRT分别为(73.43±2.37)和(23.39±1.32)min。结论 ADM-CS-NPs鼻腔给药可增加药物脑内浓度,有效实现脑内递药,同时由于纳米粒的缓释作用,可延长脑内有效药物浓度的持续时间,发挥长效作用。
Aim To investigate the brain pharmacokinetics of adriamycin hydrochloride chitosan nanoparticles(ADM-CS-NPs) via intranasal administration in rats.Methods ADM-CS-NPs were prepared by ion-facilitated gelation process.Hippocampus dialysate samples were continuously collected by brain microdialysis technique in awake freely-moving rats via intranasal or intravenous administration.The drug concentration in dialysates were detected by HPLC after administration of ADM-CS-NPs and adriamycin hydrochloride solution(ADM-Sol)(i.v.or i.n.).The pharmacokinetic parameters were calculated and statistically analyzed.Results The pharmacokinetic parameters of ADM-CS-NPs via i.n.and i.v.administration were as follows: Tmax were(300.00±26.12) and(180.00±19.11) min,Cmax were(93.00±8.53) and(19.11±1.91) mg·L-1,AUC0→11h were(17809.05±650.24) and(5159.97±120.59) mg·h·L-1,MRT were(390.49±6.87) and(281.53±4.99) min,respectively.The pharmacokinetic parameters of ADM-Sol via i.n.and i.v.administration were as follows: Tmax were(20.00±2.91) and (20.00±2.00) min,Cmax were(90.00±7.31) and(10.70±0.96) mg·L-1,AUC0→11h were(4736.70±53.40) and(312.68±4.99) mg·h·L-1,MRT were(73.43±2.37) and(23.39±1.32) min,respectively.Conclusion i.n.administration of ADM-CS-NPs both increases the drug concentration and prolongs the drug retention time in cerebral fluids,resulting in more effective brain delivery of ADM compared with i.v.administration.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2012年第7期994-999,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 30371781
30772793)
国家教育部博士点基金资助项目(No 20080344001)
关键词
盐酸阿霉素
壳聚糖
纳米粒
鼻腔给药
微透析
脑内药动学
大鼠
adriamycin hydrochloride; chitosan; nanoparticles; intranasal administration; microdialysis; brain pharmacokinetics; rats