高等学校化学学报 ›› 2015, Vol. 36 ›› Issue (5): 1025.doi: 10.7503/cjcu20140992

• 高分子化学 • 上一篇    

双重载药多层海藻酸盐-壳聚糖缓释微球的制备及体外释放

杨军星1, 王琦1, 王媛媛1, 韩舒1, 姚佳伟1, 邵思奇1, 王敬龙1, 刘志辉1(), 郭玉鹏2   

  1. 1. 吉林大学口腔医院, 长春130021
    2. 吉林大学化学学院, 长春130012
  • 收稿日期:2014-11-10 出版日期:2015-05-10 发布日期:2015-04-15
  • 作者简介:联系人简介: 刘志辉, 男, 博士, 副教授, 主要从事牙颌面组织缺损的系统重建及相关医药产业开发研究. E-mail: liuzhihui1975@sina.com
  • 基金资助:
    吉林省中青年科技创新领军人才及团队项目(批准号: 20130521008JH)、 吉林省重点科技攻关计划项目(批准号: 20140104066SF)、 吉林省医药产业推进计划项目(批准号: 20140311088YY)、 吉林大学研究生创新研究计划(批准号: 2014069)和吉林大学大学生创新创业训练计划项目(批准号: 2013A78272)资助

Preparation and in vitro Release of Multilayer Alginate Chitosan Microspheres Loading VEGF and Vancomycin

YANG Junxing1, WANG Qi1, WANG Yuanyuan1, HAN Shu1, YAO Jiawei1, SHAO Siqi1, WANG Jinglong1, LIU Zhihui1,*(), GUO Yupeng2   

  1. 1. Stomatology Hospital, Jilin University, Changchun 130021, China
    2. College of Chemistry, Jilin University, Changchun 130012, China
  • Received:2014-11-10 Online:2015-05-10 Published:2015-04-15
  • Contact: LIU Zhihui E-mail:liuzhihui1975@sina.com

摘要:

采用滴注法将海藻酸钠与钙离子交联, 制成负载血管内皮生长因子(VEGF)的藻酸钙核心球, 利用层层自组装技术在核心球的表面依次包覆壳聚糖、 海藻酸和壳聚糖, 壳聚糖中负载万古霉素(VAN), 形成多药载药缓控体系. 采用正交实验考察海藻酸钠浓度、 钙离子浓度及壳聚糖浓度对VEGF和VAN的药物包封率和载药量的影响, 优化了制备工艺. 采用扫描电子显微镜观察多层微球的表面、 截面形貌及粒径, 采用傅里叶变换红外光谱检测海藻酸盐与壳聚糖的自组装情况, 分别采用酶联免疫吸附(ELISA)双抗体夹心法和紫外分光光度法检测VEGF和VAN的包封率、 载药量及体外释放情况. 结果表明, 海藻酸钠最优浓度为0.04 g/mL, 氯化钙最优浓度为0.15 g/mL, 壳聚糖最优浓度为0.01 g/mL. 微球光滑圆整, 均质实心, 直径900~1100 μm, VEGF的包封率达61.31%, VAN的包封率为3.48%. 体外释放实验结果表明, VEGF缓释时间为15.5 d, 并出现2个释放高峰; VAN缓释时间为4.5 d, 释药情况平稳持续, 无明显突释. 双重载药多层包覆微球兼具控制感染和促进血管生成两种潜能, 有望应用于组织工程骨的基础研究和临床实践.

关键词: 血管内皮生长因子, 万古霉素, 多层包覆微球, 药物缓释, 海藻酸, 壳聚糖

Abstract:

The core ball carrying vascular epithelial growth factor(VEGF) was first prepared by crosslinking of alginate and calcium. Then, chitosan, alginate, and chitosan again were coated on the surface of the core ball layer by layer using self-assembly technology, which constituted a multi-drug loaded release-controlled system at last, and vancomycin was loaded in the chitosan layer. The effect of the concentration of alginate, calcium and chitosan on microspheres’ morphology, size, drug loading and in vitro release was studied by an orthogonal experiment to find the best formula design. Morphologies of the surface and cross section and dia-meter were observed by scanning electron microscopy(SEM). Infrared absorption spectrum of the multilayer microspheres was also detected by Fourier transformed infrared spectrometer(FTIR). The result showed that the best concentrations of alginate, calcium and chitosan were 0.04, 0.15 and 0.01 g/mL, respectively. And in this case, the multilayer microspheres were typical spherical with smooth surface and the internal solid structure with a diameter ranging from 900 to 1100 μm. The entrapment efficiency of VEGF and vancomycin was 61.31% and 3.48%, respectively. In vitro, the release of VEGF could be sustained stably for up to 15.5 d with two releasing peak, which is surprising and exciting. As well, the release of vancomycin lasted for 4.5 d, which also meets the clinical needs. The research indicates that VEGF and vancomycin loaded multilayer microspheres possess good controlled release characteristics and have the potentials of controlling infection and promoting vascularization at the same time, which is hopeful for basic research and clinical application of tissue engineering bone(TEB).

Key words: Vascular epithelial growth factor, Vancomycin, Multilayer microspheres, Drug controlled release, Alginate, Chitosan

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