环孢素A-Eudragit S100纳米粒的制备及其体内外评价  

Study on Preparation of CyA-Eudragit S100-Nanoparticles and Its Characteristics in Vivo and in Vitro

作　　者：杨志强[1] 潘萍[1] 许洁[1] 张学农[1] 陈亚根[1] 张健康[1] 魏妙[1] 

机构地区：[1]苏州大学药学院,江苏苏州215123

出　　处：《中国药学杂志》2008年第23期1798-1803,共6页Chinese Pharmaceutical Journal

基　　金：江苏省科技厅社会发展项目资助(BS200522);江苏省高校高新技术产业发展项目资助(JHB05-46);江苏省卫生厅招标课题(编号:H200630);国家大学生创新实践课题(57315420)

摘　　要：目的制备环孢素A-Eudragit S100纳米粒,并考察相关特性;以新山地明(Neoral()为参比制剂,考察大鼠体内药动学及相对生物利用度。方法以溶剂-非溶剂法联合冷冻干燥技术制备环孢素A-Eudragit S100纳米粒(CyA-NP)胶体溶液及其冻干粉末(Fd-CyA-NP);动态透析法研究其体外释药动力学;以新山地明(Neoral)为对照,大鼠分别灌胃3种制剂后,HPLC测定全血中的CyA浓度,3P97程序计算药动学参数。结果CyA-NP和Fd-CyA-NP的平均粒径分别为(44.8±3.2)和(55.7±3.6)nm;包封率大于90%;电镜下呈均匀规则的圆球形;且2种制剂在pH>6.0的释放介质中释药速率明显增大,具有显著pH敏感性;3种制剂均符合二室模型,CyA-NP和Fd-CyA-NP的相对生物利用度分别为Neoral(的162.1%和130.1%。结论以pH敏感性材料Eudragit S100为载体有望开发成一种高效、低毒的环孢素A纳米制剂。OBJECTIVE To study the preparation and pharmaceutical characteristics of cyclosporine A-Eudragit S100- nanoparticles （CyA-NP） in vitro and in vivo by using Neoral as reference preparation. METHODS CyA-NP were prepared with quasi-emulsion solvent diffusion technique and freeze-drying technique. Dynamic dialyse method was used to study the release dynamics of the three kinds of nanoparticles in vitro. The bioavailability of CyA-NP and freeze-drying nanoparticles was determined by HPLC and its pharmacokinetics parameters were calculated by 3P97 program. RESULTS The particle sizes of CyA-NP and Fd-CyA-NP were （44. 8±3.2） and （55.7 ± 3.6） nm. The encapsulation efficiency of CyA was 90%. The drug-loaded nanoparicles were spherical observed by the transmission electric microscope. The release study in vitro showed evidently pH-sensitive when the medium pH were over 6.0. The relative bioavailability of CyA-NP and Fd-CyA-NP were 162. 1% and 130.1% compared with Neoral. CONCLUSION pH-sensitive Eudragit S100 was a potential carrier material in developing a high performance CyA nanometer system with low toxicity.

关 键 词：环孢素A pH敏感性纳米粒 冻干粉末 相对生物利用度 

分 类 号：R944[医药卫生—药剂学]