明胶微球/磷酸镁基骨水泥复合药物缓释体系的构建

doi:10.15541/jim20160553

无机材料学报 ›› 2017, Vol. 32 ›› Issue (6): 655-660.DOI: 10.15541/jim20160553 CSTR: 32189.14.10.15541/jim20160553

明胶微球/磷酸镁基骨水泥复合药物缓释体系的构建

余素春, 喻莹, 戴红莲

(武汉理工大学材料复合新技术国家重点实验室, 武汉 430070)

收稿日期:2016-10-08 修回日期:2016-11-14 出版日期:2017-06-20 网络出版日期:2017-05-27
作者简介:余素春(1992–), 女, 硕士研究生. E-mail: yscstst@foxmail.com
基金资助:
国家自然科学基金重点项目(81190133);湖北省自然科学基金(2015CFB551);湖北省科技支撑计划(2015BAA085);武汉市应用基础研究计划(2015060101010032)

Construction of Gelatin Microsphere / Magnesium Phosphate Bone Cement Composite Drug Sustained Delivery System

YU Su-Chun, YU Ying, DAI Hong-Lian

(State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan 430070)

Received:2016-10-08 Revised:2016-11-14 Published:2017-06-20 Online:2017-05-27
About author:YU Su-Chun. E-mail: yscstst@foxmail.com
Supported by:
National Natural Science Foundation of China(81190133);Natural Science Foundation of Hubei Province (2015CFB551);Science and Technology Support Program of Hubei Province(2015BAA085);Wuhan Applied Basic Research Program(2015060101010032)

摘要/Abstract

摘要：

采用乳化交联法制备出粒径主要分布在100~300 μm的载药明胶微球, 分析了交联剂含量、药物含量和转速对载药率和包封率的影响及药物含量和转速对微球粒径的影响。对载药明胶微球与磷酸镁基骨水泥进行复合, 探讨微球降解过程中复合体系孔隙率的变化及其在体外药物释放的规律, 以期获得一种具有药物缓释性能的多孔磷酸镁基复合骨水泥。结果表明, 随着葡萄糖浓度增加, 载药率和包封率先上升再下降; 随着药物含量的增加, 载药率保持上升, 包封率先上升后下降; 随着转速增加, 载药率和包封率均下降。综合分析, 在转速为400 r/min、葡萄糖浓度为0.5 g/mL、药物与明胶质量比为1:2的条件下制备的载药明胶微球载药量较高, 且粒径合适。将复合不同比例该载药微球的磷酸镁基骨水泥浸泡在Tris-HCl缓冲溶液中进行体外药物释放研究, 结果表明: 在释放前期(0~10 h)药物释放速率较快, 之后药物释放明显减缓。7 d后, 微球几乎降解完全, 药物释放率达到60%~89%, 达到了一定的药物缓释效果。

关键词: 明胶微球, 载药, 磷酸镁基骨水泥, 药物缓释

Abstract:

Emulsification crosslinking method was applied to prepare drug-loaded gelatin microspheres, of which the particle size was mainly between 100-300 μm. The influence of the crosslinking agent content, drug content and rotation speed on the drug-loading rate and encapsulation efficiency and the influence of the drug content and rotation speed on the microspheres’ diameter were analyzed. The drug-loaded gelatin microspheres were deliberately combined with magnesium phosphate cement to produce porous magnesium phosphate composite bone cement with drug slow-release property, and then the changes of porosity of the composite system in the process of microsphere degradation and the drug release characteristics of the composite system in vitro were both explored. Results show that with the increase of glucose concentration, both the drug-loading rate and encapsulation efficiency increase firstly and then decrease, while both the drug content and the drug-loading rate increase and the encapsulation efficiency increases firstly and then decreases. Both the drug-loading rate and encapsulation efficiency decrease with the increase of rotation speed. Comprehensive analysis show that the gelatin microspheres with high drug-loading rate and suitable diameter can be obtained under the condition of rotation speed of 400 r/min, glucose concentration of 0.5 g/mL and the mass ratio of drug to gelatin of 1:2. The drug release characteristics in vitro were studied by immersing the magnesium phosphate cement, which was combined with different proportions of drug-loaded microspheres, into the Tris-HCl buffer solution. Results show that in the early releasing stage of 1-10 h, the drug release rate is rapid and then it obviously slows down. After being released for 7 d, microspheres almost degraded completely and the drug release ratio reaches 60%-89%. Drug slow-release property is achieved to some extent.

Key words: gelatin microspheres, drug loading, magnesium phosphate based bone cement, drug sustained delivery

中图分类号:

TB321
R318

余素春, 喻莹, 戴红莲. 明胶微球/磷酸镁基骨水泥复合药物缓释体系的构建[J]. 无机材料学报, 2017, 32(6): 655-660.

YU Su-Chun, YU Ying, DAI Hong-Lian. Construction of Gelatin Microsphere / Magnesium Phosphate Bone Cement Composite Drug Sustained Delivery System[J]. Journal of Inorganic Materials, 2017, 32(6): 655-660.

图/表 10

图1 葡萄糖含量对微球载药率和包封率的影响

Fig. 1 Effects of glucose content on drug-loading rate and entrapment efficiency for microsphere

图2 药物含量对微球载药率和包封率的影响

Fig. 2 Effects of drug content on drug-loading rate and entrapment efficiency for microsphere

图3 药物含量对微球粒径的影响

Fig. 3 Effects of drug content on microspheres’ diameter

图4 转速对微球载药率和包封率的影响

Fig. 4 Effects of rotation speed on drug-loading rate and entrapment efficiency

图5 转速对微球粒径的影响

Fig. 5 Effects of rotation speed on microspheres’ diameter

图6 MPBC骨水泥固化24 h后的SEM照片

Fig. 6 SEM image of MPBC bone cements hardened for 24 h

图7 载药明胶微球对骨水泥降解率的影响

Fig. 7 Effect of drug-loaded gelatin microspheres on bone cement degradation rate

图8 载药明胶微球对骨水泥孔隙率的影响

Fig. 8 Effect of drug-loaded gelatin microspheres on bone cement porosity

图9 降解1 d(a)、7 d(b)的MPBC-8的断面SEM照片

Fig. 9 Cross-sectional SEM images of MPBC-8 bone cements on the 1 d (a) and 7 d (b) of degradation

图10 复合磷酸镁基骨水泥的药物释放曲线

Fig. 10 Drug release profile of the complex magnesium phosphate bone cement

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明胶微球/磷酸镁基骨水泥复合药物缓释体系的构建

Construction of Gelatin Microsphere / Magnesium Phosphate Bone Cement Composite Drug Sustained Delivery System

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