环孢素A pH敏感性纳米粒的制备与大鼠口服药代动力学  

Preparation of cyclosporine A pH sensitive nanoparticles and oral pharmacokinetics in rats

作　　者：戴俊东 [1] 王学清 [1] 张涛  孟萌 [1] 张烜 [1] 吕万良 [1] 张强 [1] 

机构地区：[1]北京大学,药学院,北京,100083 [2]华北制药集团,新药研发中心,河北,石家庄,050015

出　　处：《药学学报》2004年第12期1023-1027,共5页Acta Pharmaceutica Sinica

基　　金：863计划资助项目(2001AA218061)

摘　　要：目的　研究环孢素A(CyA)pH敏感性纳米粒的制备工艺与口服药代动力学性质。方法　采用改良的乳 化 溶剂扩散技术(QESD)制备CyApH敏感性纳米粒;经大鼠灌胃给药,HPLC法测定全血药物浓度,计算口服相对 生物利用度。结果　经3P87程序拟合,确定CyA在大鼠体内的药代动力学过程为二室模型;与Neoral微乳相比, CyA E100,CyA L100,CyA L100 55和CyA S100纳米粒的相对生物利用度分别为94.8%,115.2%,113.6%和 132.5%。结论　经统计分析,CyA S100纳米粒可以显著改善CyA的生物利用度(P<0.05),而CyA L100 55纳米 粒,CyA L100纳米粒和CyA E100纳米粒与Neoral微乳相比无显著性差异。实验结果表明,pH敏感性纳米粒有望成 为促进蛋白、多肽类药物及难溶性药物口服吸收的有效载体。Aim To study the preparation conditions and its oral pharmacokinetic characteristics of cyclosporine A (CyA) pH sensitive nanoparticles. Methods The CyA pH sensitive nanoparticles were prepared by the quasi-emulsion solvent diffusion technique (QESD). Male Sprague-Dawley (SD) rats weighing ( 250±20) g were selected and randomly divided into five groups. The bioavailability of CyA from nanoparticles and Neoral microemulsion were assessed at a dose of 15 mg·kg -1 by gavage. The concentration of CyA in whole blood samples was detected by HPLC to evaluate the relative bioavailability of CyA pH sensitive nanoparticles. Results The blood concentration profiles of CyA pH sensitive nanoparticles in rats fitted to two compartment models using 3P87 pharmacokinetic calculation program. Compared with the Neoral microemulsion,the relative bioavailability of CyA was 94.8%,115.2%,113.6% and 132.5% for CyA-E100,CyA-L100,CyA-L100-55 and CyA-S100 nanoparticles respectively. Conclusion CyA-S100 nanoparticles was shown to significantly improve the oral bioavailability of CyA compared with Neoral microemulsion ( P <0.05). While there were no significant differences between Neoral microemulsion and other CyA pH sensitive nanoparticles. With these results,the potential of pH-sensitive nanoparticles for the oral delivery of CyA was confirmed. Furthermore,this formulation approach can be used to improve the oral bioavailability of other poorly soluble and poorly absorbable drugs.

关 键 词：环孢素A pH敏感性纳米粒 口服生物利用度 优特奇 新山地明 

分 类 号：R943.4[医药卫生—药剂学] R969.1[医药卫生—药学]