Wang Xue-Qing, Dai Jun-Dong, Chen Zhen, Zhang Tao, Xia Gui-Min, Nagai T, Zhang Qiang
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100083, People's Republic of China.
J Control Release. 2004 Jul 7;97(3):421-9. doi: 10.1016/j.jconrel.2004.03.003.
The pH-sensitive cyclosporine A (CyA) nanoparticles were prepared by the solvent displacement method with enteric dissolved polymer of hydroxypropyl methylcellulose phthalate (HPMCP; including HP50 and HP55). The CyA nanoparticles were analyzed by HPLC for yield and encapsulation efficiency, dynamic light scattering for particle size and transmission electron microscopy (TEM) for morphology. The bioavailability of CyA-HP50 and CyA-HP55 nanoparticle colloids were evaluated in rats, compared with the current available CyA microemulsion (Neoral). The bioavailability of CyA-HP55 nanoparticle colloids with various suspending agents was also investigated. The results obtained demonstrated that the pH-sensitive CyA nanoparticles with a particle size of 50-60 nm and encapsulation efficiency over 95% could be reproducibly prepared. The bioavailability of CyA-HP50 and CyA-HP55 nanoparticle colloids calculated by the AUC(0-72) were 82.3% and 119.6%, similar to the reference of Neoral, while the bioavailability of CyA-HP55 nanoparticle colloids was found to be higher than that of CyA-HP50 nanoparticle colloids. The increase of mean residence time (MRT) and the decrease of elimination constant of the central compartment (K10) for both CyA-HP50 and CyA-HP55 nanoparticle colloids compared with the reference indicated significant sustained release of CyA from the nanoparticles. The effects of the suspending agents on the bioavailability of CyA-HP55 nanoparticles were observed, and the bioavailability decreased as the concentration of suspending agents or the viscosity of the nanoparticle colloids increased.
采用溶剂置换法，以肠溶溶解聚合物邻苯二甲酸羟丙基甲基纤维素（HPMCP，包括HP50和HP55）制备了pH敏感型环孢素A（CyA）纳米粒。通过高效液相色谱法分析CyA纳米粒的产率和包封率，通过动态光散射法分析粒径，通过透射电子显微镜（TEM）分析形态。在大鼠中评估了CyA-HP50和CyA-HP55纳米粒胶体的生物利用度，并与市售的CyA微乳剂（新山地明）进行比较。还研究了不同悬浮剂对CyA-HP55纳米粒胶体生物利用度的影响。结果表明，可重复性地制备出粒径为50-60nm、包封率超过95%的pH敏感型CyA纳米粒。通过AUC(0-72)计算得出，CyA-HP50和CyA-HP55纳米粒胶体的生物利用度分别为82.3%和119.6%，与新山地明参考值相似，而CyA-HP55纳米粒胶体的生物利用度高于CyA-HP50纳米粒胶体。与参考值相比，CyA-HP50和CyA-HP55纳米粒胶体的平均驻留时间（MRT）增加，中央室消除常数（K10）降低，表明CyA从纳米粒中有显著的缓释效果。观察到悬浮剂对CyA-HP55纳米粒生物利用度的影响，随着悬浮剂浓度或纳米粒胶体粘度的增加，生物利用度降低。
