环孢素A纳米粒在小鼠体内的药动学及组织分布  

Pharmacokinetics and Biodistribution of Cyclosporine A Nanoparticles in Mice

作　　者：房志刚[1] 陈亚根[1] 张健康[1] 魏妙[1] 张学农[1,2] 

机构地区：[1]苏州大学药学院,苏州市215123 [2]苏州利元医药科技有限公司,苏州市215002

出　　处：《中国药房》2010年第9期796-799,共4页China Pharmacy

基　　金：国家科技支撑计划课题资助项目(2006BAI09B00);国家科技部科技型中小企业技术创新基金(07C26223201333);江苏省卫生厅招标课题(H200630);国家大学生创新实践课题(57315420)

摘　　要：目的:研究环孢素A纳米粒(CyA-NP)在小鼠体内组织分布,并与市售新山地明微乳制剂(Neoral)的组织分布特征进行比较。方法:取小鼠120只,随机分为20组,每组6只,前10组小鼠按25mg·kg-1的剂量灌胃给予Neoral溶液,后10组灌胃给予等剂量的CyA-NP溶液,于给药后不同时间摘眼球取血及制备各组织样品,各样品中的药物采用液-液萃取法提取,建立高效液相色谱(HPLC)法测定血液及各组织中不同时间的药物浓度,以各组织药动学参数和靶向参数为评价指标,对2种制剂在小鼠体内的分布特征和靶向性进行评价。结果:血药浓度测定方法的回收率均大于72%,日内、日间精密度良好;2种制剂在小鼠体内均符合口服吸收二室模型;与Neoral比较,CyA-NP给药后CyA在血液及各组织中药物浓度较快达到峰值,相对生物利用度为162.5%;在体内药物浓度分布趋势为肝>心>肾>脾>肺,在肝中无蓄积。结论:与Neoral比较,CyA-NP体内分布迅速,组织分布广泛,促进了药物口服吸收,改变了CyA在体内的组织分布,有助于提高临床用药水平,对局部脏器移植有更好的疗效。OBJECTIVE： To study in vivo biodistribution behavior and targeting performance of cyclosporine A nanoparticles （CyA-NP） in mice and to compared it with Neoral. METHODS： 120 mice were randomized into 20 groups with 6 per group. 10 groups were administrated with 25 mg.kg^-1 Neoral via i.g. gtt. Other 10 groups were given 25 mg.kg^-1 CyA-NP via i.g. gtt. The liquid-liquid extraction method was used in biological samples extraction. The HPLC method was established to determine the concentration of CyA in blood and tissues of the mice at different time points. The tissues distribution and targeting efficiency were evaluated with pharmacokinetic parameters and targeting parameters as evaluation index. RESULTS： The recovery was over 72%, and the intra-day and inter--day RSD were less than 15%. The concentration-time data of Neoral and CyA-NP were fitted with two-compartment model in mice. Compared with Neoral, the relative bioavailability of CyA-NP was 162.5% and reached the concentration peak earlier. The descending sequence of CyA-NP levels in tissues was liver, heart, kidney, spleen and lung. It didn＇ t accumulate in liver. CONCLUSION： As compared with Neoral, CyA-NP deliver quickly and extensively to promote absorption of oral drug and change the distribution of CyA in tissue. It is helpful to improve clinical efficacy of CyA in partial organ transplantation.

关 键 词：环孢素A 纳米粒 新山地明 小鼠 组织分布 靶向性 

分 类 号：R979.5[医药卫生—药品] R969.1[医药卫生—药学]