中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (8): 1386-1391.doi: 10.3969/j.issn.1673-8225.2010.08.014

• 药物控释材料 drug delivery materials • 上一篇    下一篇

包裹多柔比星微球骨水泥的制备及其表征

张  辉1，薛忠林2，靳安民1，李  森1，叶建东3   

  1. 1南方医科大学珠江医院骨科，广东省广州市   510280；   2江门市中心医院脊柱骨科，广东省江门市 529000；3 华南理工大学材料与工程学院，广东省广州市   510640
  • 出版日期:2010-02-19 发布日期:2010-02-19
  • 作者简介:张 辉☆，男，1968年生，江西省信丰县人，汉族，2005年解放军第一军医大学毕业，博士，副主任医师，主要从事脊柱、脊髓的损伤与防治的研究。 zhanghuixf@163.com
  • 基金资助:

    广东省科技计划项目课题（2007B031003009）。

Preparation and characteristics of doxorubicin microspheres-coated bone cement

Zhang Hui1, Xue Zhong-lin2, Jin An-min1, Li Sen1, Ye Jian-dong3   

  1. 1 Department of Orthopaedics, Zhujiang Hospital, Southern Medical University, Guangzhou   510280, Guangdong Province, China; 2 Department of Spinal Orthopaedics, Jiangmen Central Hospital, Jiangmen   529000, Guangdong Province, China; 3 College of Material Science and Engineering, South China University of Technology, Guangzhou   510640, Guangdong Province, China
  • Online:2010-02-19 Published:2010-02-19
  • About author:Zhang Hui☆, Doctor, Associate chief physician, Department of Orthopaedics, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, Guangdong Province, China zhanghuixf@163.com
  • Supported by:

    Science and Technology Planning Project of Guangdong Province, No. 2007B03 1003009*

PDF

416

被引次数

6

摘要：

背景：不同材料的骨水泥其性能不同，治疗的效果也会有所不同。
目的：对比观察CPC、CPC/D、CPC/M/D 3种材料的性能，探讨包裹多柔比星微球骨水泥的制备方法。
方法：采用复乳溶剂挥发法制备多柔比星微球，将多柔比星药物微球与CPC粉末以3∶7的比例均匀混合，制备成柱状包裹药物微球骨水泥。实验分为3组：①CPC组材料中只有骨水泥，不含药物和药物微球。②CPC/D组含有多柔比星药物的骨水泥。③CPC/M/D组包裹有多柔比星药物微球的骨水泥。用扫描电镜在不同放大倍数下观察样本结构特征，测量微球的粒径。采用X射线衍射分析仪测试样品的化学成分。分别对3组骨水泥在25 ℃和37 ℃下凝结时间进行测定，并计算可注射性和孔隙率。将试件置于万能生物力学试验机上进行最大抗压强度的测定，记录标本样条的最大抗压强度和断裂强度。
结果与结论: PLGA微球(100~150 µm)表面光整圆滑,骨水泥与药物混合后的微结构变化不大，无法判断药物在骨水泥中的位置和特征性表现。载微球骨水泥(100~150 µm)的结构疏散，均匀分布于CPC粉末之间。3种样品的XRD谱线与标准的羟基磷灰石的XRD谱线一致，其主峰位于XRD谱线32°附近。加入药物和微球并没有新的相产生。3种骨水泥刚投入生理盐水中材料均无崩解，但24 h后包裹微球的骨水泥表面有明显溃散，材料不完整。CPC/M/D组凝结时间最长，CPC组凝结时间最短；37 ℃时，凝结时间较长；终凝时间较长，在CPC/M/D组可达45 min左右。加入药物微球的CPC/M/D组可注射性能最好。CPC/M/D组的孔隙率最大，CPC组最小。CPC中加入药物微球后，其孔隙率可显著增加达61.67%。CPC组屈服应力最大，CPC/M/D组最小。当多柔比星原药和药物微球加入磷酸钙骨水泥后，其强度会有所降低，但两者之间差异并不显著。结果证实包裹多柔比星微球骨水泥的制备方法可靠，产物具有理想的结构和良好的性能。

关键词: 磷酸钙骨水泥, 微球, 多柔比星, 制备, 表征, 生物活性骨水泥材料

Abstract:

BACKGROUND: Bone cement coated by different materials has various characteristics and causes varying therapeutic effects.
OBJECTIVE: By comparing characteristics of CPC, CPC/D, and CPC/M/D3 to investigate the preparation of doxorubicin microspheres-coated bone cement.
METHODS: Doxorubicin microspheres were prepared with multiple emulsion solvent volatilixation method. Doxorubicin microspheres were mixed with CPC as the ratio of 3:7 to prepare doxorubicin microspheres-coated bone cement. The samples were randomly divided into three groups: CPC group, containing bone cement alone; CPC/D group, containing doxorubicin; CPC/M/D group, containing doxorubicin microspheres. Scanning electron microscope at varying magnification was used to observe structural characteristics and measure the diameter of microspheres. X-ray diffraction was used to estimate the extent of CPC and CPC/M/D samples. The initial and final setting time of cement samples in the three different groups was measured at  25 ℃ and 37 ℃ respectively. The injectability and interval porosity of different samples were tested. The compressive strength of the specimens was measured using a universal material testing machine to record the maximal compressive strength and breaking strength.
RESULTS AND CONCLUSION: PLGA microspheres (100-150 µm) were globular and the surface was slick and sly. Microstructure of bone cement was not obviously changed following mixing with drugs, thus the location and characteristics of drugs in bone cement were not determined. Microspheres-coated bone cement (100-150 µm) was distributed among CPC powder. All the X-ray diffraction pattern of three different samples was in coincidence with standard X-ray diffraction pattern of hydroxyapatite, i.e., the major peak was located near 32°. Additional drugs and microspheres did not cause new phases. Obvious collapsing was not observed in the three samples following immediately adding in saline, but the collapsing appeared in both CPC/D and CPC/M/D samples after 24 hours. The setting-up time of CPC/M/D was the longest, but that of CPC was the shortest. On the other hand, the setting-up time was the longest at 37 ℃. The final setting-up time of CPC/M/D group was 45 minutes. The doxorubicin microspheres-coated bone cement showed the best property of injectability among the three kinds of cement. The interval porosity was the highest in the CPC/M/D group but the lowest in the CPC group. Interval porosity of doxorubicin microspheres-coated bone cement was up to 61.67%. The yield stress was the strongest in the CPC group but the weakest in the CPC/M/D group. Additionally, the yield stress of calcium phosphate cement dramatically decreased while doxrorubicin microspheres were coated. However, there was no significant difference between them. The preparation of doxorubicin microspheres-coated bone cement was reliable and the product had good structures and properties.

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