不同聚乙二醇相对分子质量对包载羟基喜树碱的PEG-PHDCA纳米囊泡 体外释放和体内药动学行为的影响  

Influence of PEG chain length on in vitro drug release and in vivo pharmacokinetics of hydroxycamptothecin(HCPT) loaded PEG-PHDCA niosomes

作　　者：施斌[1] 方超[1] 游美羡 裴元英[1] 

机构地区：[1]复旦大学药学院药剂学教研室,上海200032

出　　处：《中国药学杂志》2005年第21期1643-1646,共4页Chinese Pharmaceutical Journal

基　　金：上海市科技发展基金纳米专项(0243nm067)

摘　　要：目的探讨不同聚乙二醇(PEG)相对分子质量对包载羟基喜树碱的聚乙二醇化聚十六烷基氰基丙烯酸酯(PEG-PHDCA)纳米囊泡体内外行为的影响。方法采用薄膜分散-水化超声法制备了羟基喜树碱的PEG-PHDCA纳米囊泡,在研究该纳米囊泡的形态、粒径、载药量、包封率、冷冻干燥工艺后对其体外释药特征及体内药动学参数进行测定。结果纳米囊泡的载药量、体外释药、体内药动学行为等与不同PEG相对分子质量有关。随着PEG相对分子质量从2000上升到10000,囊泡的载药量从3.04%下降到1.99%;体外释药符合Higuchi方程,随PEG相对分子质量的上升,囊泡的释药速率加快;在SD大鼠的药动学实验中,血药浓度-时间曲线符合二室开放药动学模型,PEG相对分子质量为2000,5000,10000的PEG-PHDCA纳米囊泡可分别将HCPT的血浆半衰期从0.72h延长到7.17,11.46,6.39h(P<0.001),AUC分别为HCPF的8.40,24.50,6.24倍(P<0.001)。结论在本实验范围内,PEG相对分子质量为5000的PEG-PHDCA载药纳米囊泡体外具有一定的缓释作用,体内具有最佳的长循环效果。OBJECTIVE To investigate the influence of PEG chain length on in vitro and in vivo behaviors of Hydroxycamptothecin （HCPT） loaded PEG-PHDCA niosomes.METHODS PEG-PHDCA niosomes were prepared by film-dispersion and hydration-sonication method and lyophilized. The niosomes were further characterized in terms of structure, particle size, drug loading coeffiecint, drug encapsulation rate, in vitro drug release and in vivo pharmacokinetics. RESULTS The parameters of drug loading coeffiecint, in vitro drug release and in vivo Pharmacokinetics were proved to be related to PEG chain length. When PEG MW increased from 2 000 to 10 000, the drug loading coefficient decreased from 3.04 % to 1.99 %. The in vitro drug release was fitted well by Higuchi equation and the drug release was accelerated with the PEG chain length. The plasma concentration-time curve of HCPT was fitted by a two compartment open model. The niosomes of PEGPHDCA with PEG chain length of 2 000, 5 000 and 10 000 prolonged the half life of HCPT in plasma from 0.72 h to 7.17, 11.46 and 6.39 h （ P 〈 0.001 ）, respectively; while AUCs were 8.40, 24.50 and 6.24-fold of that of HCPT（ P 〈 0.001 ）, respectively. CONCLUSION PEG5000-PHDCA niosomes show a sustained release pattern in vitro and best stability effect in vivo.

关 键 词：薄膜分散-水化超声法 羟基喜树碱 长循环 药动学 

分 类 号：R943.4[医药卫生—药剂学]