超临界流体技术制备5_氟尿嘧啶_吲哚美辛_聚乳酸缓释微球_张严之

复合材料学报第28卷 第1期 2月 2011年A cta M ateriae Co mpo sitae Sinica

V ol 28

N o 1

F ebr uar y

2011

文章编号:1000-3851(2011)01-0021-05

收到初稿日期:2010-02-04;收到修改稿日期:2010-05-05

通讯作者:尹光福,教授,研究方向:生物医学材料 E mail:yin gf@s

超临界流体技术制备5 氟尿嘧啶吲哚美辛

聚乳酸缓释微球

张严之,李奎锋,黄 婷,黄 锐,康云清,尹光福

*

(四川大学材料科学与工程学院,成都610064)

摘 要: 为了考察药物5 氟尿嘧啶(5 F u)与吲哚美辛(ID M C)的协同作用,采用超临界流体强制分散溶液技术(SEDS),以二氯甲烷/二甲亚砜为共溶剂,制备了复合5 F u 和ID M C 的L 聚乳酸(PL L A)微球。利用单因素法探索了制备复合微球的最佳外部条件,通过表面形貌、载药量、粒径分布、释放性能的检测和体外细胞实验来表征微球的各项性能。结果表明:当共溶剂二氯甲烷/二甲亚砜比例为30 1时,制备该微球的优化条件为39 、14M Pa;微球形貌呈类球形,粒径分布在0.5~5 m;复合IDM C 后微球具有更优良的缓释效果;载药微球对A549细胞系增殖有明显的抑制作用,但与复合IDM C 前后微球共培养的2组细胞的相对生长速率(RGR)无显著性差异。

关键词: 超临界流体技术;5 氟尿嘧啶;吲哚美辛;聚乳酸;微球中图分类号: R318.08 文献标志码: A

Preparation of 5 fluorouracil indomethacin poly(L lactide)microspheres

using a novel supercritical flu id technique

ZH ANG Yanzhi,LI Kuifeng ,H U ANG T ing ,H U ANG Rui,KANG Yunqing,YIN Guangfu

*

(Colleg e o f M ater ials Science and Eng ineer ing,Sichuan U niver sity,Chengdu 610064,China )

Abstract: T o investig ate the sy ner gistic effect o f t he dr ug 5 fluor ouracil(5 F u)and indo methacin(IDM C),the micro spheres of poly (L lactide)w it h IDM C and 5 F u w ere pr epar ed by the technique of so lutio n enhanced dispersio n by supercritical CO 2(SED S),using dichlor omethane/dimet hy l sulfox ide as a cosolvent system.A single facto r met ho d w as used to ex plor e the best ex ternal conditio ns.T he mo rpholo gy ,drug loading,par ticle size distr ibut ion and r elease pr ofiles of 5 Fu -IDM C -PL L A microspher es were character ized,and the in v itr o cell cultur e was designed and perfo rmed.T he results indicat e that 39 ,14M Pa is the pr eferable condition fo r the micro spheres prepa ratio n w hen the r at io o f the cosolvent is 30 1.T he micro spheres ex hibite a g oo d spherical morpholog y,a part icle size distr ibution bet ween 0.5~5 m,w hich possess a sustained r elease pro per ty and enhanced after composit ed with IDM C.T he in vitro cell culture ex periment sho w that the drug lo aded microspheres significantly inhibite the prolifer ation of A549cell line,but the relative g row th r ate (RG R)of the tw o g roup o f cells cultur ed w ith the micro spheres before and aft er composition IDM C have no signif icant differ ence.Keywords: supercritical fluid technique;5 fluo rouracil;indomethacin;poly(L lactide);micro spheres

缓控释体系具有减少给药频率、减少剂量、降低不良反应等优越性,已引起人们的广泛研究兴趣。用超临界流体强制分散溶液技术(SEDS)制备复合微球,与传统的方法相比,具有溶剂残留量低、条件温和、周期短等优势[1-4]

。5 氟尿嘧啶(5 fluoro uracil,5 Fu)是一种临床常用抗代谢类广谱抗肿瘤药物,将其制成聚合物缓释微球,可减少给

药次数,提高利用效率,减少毒副作用。吲哚美辛(Indo methacin,IDM C)临床上用作解热镇痛及抗炎抗风湿类非甾体类消炎药,研究表明,IDMC 能显著增强5 Fu 抗肿瘤作用[5-6]。L 聚乳酸(PL LA)作为无毒、可生物降解的聚合物,已被美国FDA 批准用作药物缓、控释制剂的载体。本研究中采用SEDS 技术,以PLLA 为载体材料,二氯甲