9-硝基喜树碱口服自微乳化系统的制备与体外评价  

Preparation of 9-nitrocamptothecin self-emulsification microemulsion and in vitro cytotoxicity evaluation

作　　者：吕娟丽[1] 刘振华[2] 王坚成[1] 张强[1] 

机构地区：[1]北京大学药学院药剂系,北京100083 [2]武警总医院药剂科,北京100039

出　　处：《中国新药杂志》2008年第10期861-865,共5页Chinese Journal of New Drugs

基　　金：国家自然科学基金资助项目(30430760)

摘　　要：目的:制备9-硝基喜树碱(9-NC)口服自微乳给药系统(SMEDDS),并考察其对肿瘤细胞生长抑制作用。方法:采用伪三元相图法优化微乳处方组成,稀释法评价了9-NC SMEDDS乳化性能,并考察了9-NC SMEDDS乳化后获得的微乳制剂(9-NCME)对4种肿瘤细胞的体外细胞毒活性。结果:由油酸乙酯,Tween 80,PEG400,无水乙醇组成的9-NC SMEDDS遇水可自发形成粒径<50 nm的稳定微乳(9-NCME)。体外细胞毒研究表明,与溶液剂组(9-NCSol)和混悬液组(9-NCSu)相比,微乳制剂(9-NCME)对肿瘤细胞MDA-MDB-231,MCF-7,SKOV3和SH5Y的IC50值显著减小(P<0.01)。结论:本研究中制备的9-NCSMEDDS具备良好的自乳化性能,并可增强9-NC的体外抗肿瘤活性。Objective：To prepare the oral self-microemulsifying drug delivery system of 9-nitrocamptothecin （9-NC SMEDDS） and evaluate its in vitro cytotoxicity. Methods：9-NC SMEDDS formulation was optimized in terms of droplet size and lack of drug precipitation following aqueous dilution, using a pseudo-ternary phase diagram. Physicochemical properties of 9-NC SMEDDS and its resulted microemulsion （9-NCME） were evaluated. The in vitro cytotoxicities of 9-NCME and other 9-NC preparations （solution and suspension） were evaluated by sulforhodamine B （SRB） assay respectively. Results：A stable O/W microemulsion was made up of ethyl oleate as oil phase, Tween 80 as emulsifier, PEG 400 and ethanol as co-emulsifier, and thereafter formed spherical particles with diameter 〈 50 nm after 20-fold dilution with water phase. The ICs0 of 9-NCME on four kinds of human cancer cells （ MDA-MB-231, MCF-7,SKOV3 ,SH5Y） significantly decreased （P 〈 0.01 ） as compared to that of 9-NC solution and 9-NC suspension. Conclusion ： It indicated that 9-NC SMEDDS formulation might be a potential therapeutic drug for oral administration and could improve antitumor activity.

关 键 词：9硝-基喜树碱 自微乳化给药系统 细胞毒 

分 类 号：R943.5[医药卫生—药剂学] R979.1[医药卫生—药学]