中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (8): 1392-1396.doi: 10.3969/j.issn.1673-8225.2010.08.015

• 材料生物相容性 material biocompatibility • 上一篇    下一篇

紫杉醇-聚氰基丙烯酸二乙酯纳米胶束载体材料的可接受效应

武  莉,杨  菁,刘天军,宋存先   

  1. 中国医学科学院,北京协和医学院,生物医学工程研究所天津生物医学材料重点实验室,天津市  300192
  • 出版日期:2010-02-19 发布日期:2010-02-19
  • 通讯作者: 刘天军,博士,研究员,中国医学科学院,北京协和医学院,生物医学工程研究所天津生物医学材料重点实验室,天津市 300192
  • 作者简介:武 莉,女,1970年生,河北省兴隆县人,汉族,天津师范大学毕业,主管技师,主要从事医用生物材料研究。 wuli.7777@yahoo.com.cn
  • 基金资助:

    国家高技术研究发展计划(十一五“863”计划):检测肿瘤标志物纳米诊断试剂盒的临床试验研究(2007AA021808);国家自然科学基金资助项目:新型主动靶向双功能纳米控释系统以及用于防治血管再狭窄的研究(300800225);天津市自然科学基金资助项目:心血管再狭窄靶向紫杉醇纳米胶束的制备及靶向性能研究(08JCYBJC11200)。

Acceptability of Taxol-poly (alkyl-cyanoacrylates) micell material

Wu Li, Yang Jing, Liu Tian-jun, Song Cun-xian   

  1. Tianjin Biomedical Material Key Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin  300192, China
  • Online:2010-02-19 Published:2010-02-19
  • Contact: Liu Tian-jun, Doctor, Researcher, Tianjin Biomedical Material Key Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China
  • About author:Wu Li, Chief technician, Tianjin Biomedical Material Key Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China wuli.7777@yahoo.com.cn
  • Supported by:

    the National High Technology Research and Development Program of China (“863” Project), No. 2007AA021808*; National Natural Science Foundation of China, No. 300800225*; Natural Science Foundation of Tianjin, No. 08JCYBJC11200*

摘要:

背景:目前研究使用的聚氰基丙烯酸烷基酯,在降解过程中生成了醛类化合物,易导致一定程度的毒性与刺激作用。课题组在氰基丙烯酸酯单体中引入乙二醇取代基,合成一种新的与人体细胞结构更相容的纳米胶束载体材料—聚氰基丙烯酸乙二酯聚合物,作为脂溶性药物载体具有光明的应用前景。
目的:以聚氰基丙烯酸乙二酯聚合物为载体,制备紫杉醇-聚氰基丙烯酸二乙酯纳米胶束,验证其用于小鼠乳腺癌治疗的可接受性。
方法:超声乳化法制备不同粒径紫杉醇-聚氰基丙烯酸二乙酯纳米胶束并进行表征;建立BablC小鼠乳腺癌动物模型,分为生理盐水组和空白纳米胶束组,紫素阳性对照组,高、中、低3个紫杉醇-聚氰基丙烯酸纳米胶束剂量治疗组。对瘤体进行局部注射给药,检测紫杉醇-聚氰基丙烯酸二乙酯纳米胶束对肿瘤的抑制效果。
结果与结论:紫杉醇-聚氰基丙烯酸二乙酯纳米胶束平均粒径70 nm,药物含量为19.89%,药物体外释放能够持续达到2周以上时间。动物实验表明,在相当紫杉醇总量为30,60,90 mg/kg的3种剂量下,紫杉醇-聚氰基丙烯酸二乙酯纳米胶束给药组与生理盐水组相比具有明显的抑瘤效果(P < 0.001),抑瘤率分别为68.49%,77.03%和81.87%。提示紫杉醇-聚氰基丙烯酸二乙酯纳米胶束作为小鼠乳腺癌治疗的缓释制剂治疗效果显著,具有良好的可接受性。

关键词: 紫杉醇, 聚氰基丙烯酸二乙酯, 纳米胶束, 乳腺癌动物模型, 缓释制剂, 药物控释系统及其载体材料

Abstract:

BACKGROUND: Currently used poly (alkyl-cyanoacrylates) (PACA) produces aldehyde compound in its degradation, which is easily results in toxicity and stimulation to the body. Here, a novel Taxol-PACA micell material was synthesized, which has broad application as a kind of liposolubility drug delivery carrier.
OBJECTIVE: To verify the therapeutic efficacy of Paclitaxel-PECA micells for mouse breast cancer.
METHODS: Paclitaxel drug delivery micells were prepared by a multi-emulsification technique and were characterized for size, drug loading capacity, and in vitro release. Bablc breast cancer model mice were randomly divided into the physiological saline, vacant control, paclitaxel positive control, and Paclitaxel-PECA micells with low-dose, medium-dose, and high-dose groups. Paclitaxel and Paclitaxel-PECA micells were injected into the location of mouse breast cancer, and then the tumor inhibit rates were detected.  
RESULTS AND CONCLUSION: The mean diameter of Paclitaxel-PECA micells was 70 nm, with 19.89% loading amount of Paclitaxel. In vitro, micells maintained sustained release of Paclitaxel for 2 weeks. Compared with the physiological saline group, the Paclitaxel-PECA micells group exhibited superior tumor inhibit effects with doses of 30, 60, and 90 mg/kg (P < 0.001), which was 68.49%, 77.03% and 81.87%, respectively. The results suggested that Paclitaxel-PECA micells material has excellent acceptability as sustained-release preparation for treating mouse breast cancer.

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