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。
Abstract
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
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Key words
cyclosporine A /
pH-sensitive nanoparticle /
freeze-drying powder /
relative bioavailability
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杨志强;潘萍;许洁;张学农;陈亚根;张健康;魏妙.
环孢素A-Eudragit S100纳米粒的制备及其体内外评价[J]. 中国药学杂志, 2008, 43(23): 1798-1803
YNG Zhi-qing;PN Ping;XU Jie;ZHNG Xue-nong;CHEN Y-gen;ZHNG Jin-kng;WEI Mio.
Study on Preparation of CyA-Eudragit S100-Nanoparticles and Its Characteristics in Vivo and in Vitro[J]. Chinese Pharmaceutical Journal, 2008, 43(23): 1798-1803
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参考文献
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脚注
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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)
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