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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。
Objective To study the preparation process and oral pharmacokinetics of CyA-sensitive pH-sensitive nanoparticles. Methods CyApH-sensitive nanoparticles were prepared by modified emulsified solvent diffusion (QESD) technique. The rats were intragastrically administrated and the whole blood concentration was determined by HPLC. The relative bioavailability was calculated. Results The pharmacokinetics of CyA in rats were determined by 3P87 program and the relative bioavailability of CyA E100, CyA L100, CyA L100 55 and CyA S100 nanoparticles was compared with Neoral microemulsion Respectively 94.8%, 115.2%, 113.6% and 132.5%. Conclusions CyA S100 nanoparticles can significantly improve the bioavailability of CyA (P <0.05) by statistical analysis. However, no significant difference was observed between CyA L100 55 nanoparticles, CyA L100 nanoparticles and CyA E100 nanoparticles compared with Neoral microemulsion. The experimental results show that pH-sensitive nanoparticles are expected to be effective carriers for the oral absorption of proteins, peptides and poorly soluble drugs.