基于壳聚糖衍生物的蛋白质药物载体材料的制备及性能

doi:10.7503/cjcu20140665

高等学校化学学报 ›› 2015, Vol. 36 ›› Issue (3): 589.doi: 10.7503/cjcu20140665

• 高分子化学 • 上一篇

基于壳聚糖衍生物的蛋白质药物载体材料的制备及性能

刘圆圆¹, 黄燕¹, 吕正荣³, BOAMAH Peter-Osei¹, 张岐^1,²(), 吴静波¹, 华明清¹

1. 江苏大学化学化工学院, 镇江 212013
2. 海南大学海南省精细化工重点实验室, 海口 570228
3. 美国凯斯西储大学生物工程系, 克利夫兰 44106-7207

收稿日期:2014-07-18 出版日期:2015-03-10 发布日期:2015-02-04
作者简介:联系人简介: 张岐, 男, 博士, 教授, 博士生导师. 主要从事天然高分子药物载体材料研究. E-mail: qzhang@ujs.edu.cn
基金资助:
国家自然科学基金(批准号: 21261008, 21302071, 21204031)、江苏大学高级人才科研启动基金(批准号: 14JDG054)和海南省国际科技合作专项(批准号: KJHZ2014-05)资助

Preparation and Characterization of Chitosan Derivative Microspheres for Protein Delivery^†

LIU Yuanyuan¹, HUANG Yan¹, LU Zhengrong³, BOAMAH Peter-Osei¹, ZHANG Qi^1,^2,^*(), WU Jingbo¹, HUA Mingqing¹

1. Department of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, China
2. Hainan Provincial Key Lab of Fine Chemistry, Hainan University, Haikou 570228, China
3. Department of Biomedical Engineering, Case Western Reserve University, Cleveland 44106-7207, USA

Received:2014-07-18 Online:2015-03-10 Published:2015-02-04
Contact: ZHANG Qi E-mail:qzhang@ujs.edu.cn
Supported by:
† Supported by the National Natural Science Foundation of China(Nos.21261008, 21302071, 21204031), the Scientific Research Foundation for Advanced Talents of Jiangsu University, China(No.14JDG054) and the Hainan International Science and Technology Cooperation, China(No.KJHZ2014-05)

摘要/Abstract

摘要：

在离子液体均相体系中合成了一种新型两亲性窄分子量分布的低聚壳聚糖衍生物月桂基-琥珀酰化壳聚糖(LSCOS). 以LSCOS为载体材料, 以牛血清蛋白(BSA)为模板蛋白, 以戊二醛为交联剂, 用油包水(W/O)乳化交联法制备了包载BSA的BSA/LSCOS缓释载药微球. 通过扫描电子显微镜(SEM)、透射电子显微镜(TEM)及紫外-可见光谱(UV-Vis)研究了BSA/LSCOS比率和戊二醛/LSCOS比率对微球的形貌结构、包埋率、载药率和体外药物释放特性的影响. 结果表明, 在离子液体中合成的LSCOS包覆了BSA, 形成的微球粒径约为1 μm, 微球表面随BSA用量的增加变得光滑, 随戊二醛用量的增加变得粗糙. BSA的累积释放率与BSA包载量成正比, 与交联剂添加量成反比, 因此, 可通过控制蛋白质药物的添加比率和交联剂用量来控制蛋白质药物体外释放率.

关键词: 离子液体, 壳聚糖, 衍生物, 乳化交联法, 微球

Abstract:

A novel amphiphilic narrow molecular weight distribution and low degree of polymerization lauryl-succinyl chitosan derivative(LSCOS) was synthesized in ionic liquid homogeneous system. The LSCOS microspheres were prepared according to water-in-oil emulsification cross-linking method with LSCOS as protein-loading material and bovine serum albumin(BSA) as a model protein and glutaraldehyde as the crosslinker. The effects of the BSA/LSCOS mass ratio and glutaraldehyde/LSCOS mass ratio on the morphology structure, loading capacity(LC), loading efficiency(LE) and in vitro BSA release characteristics were investigated by means of scanning electron microscopy(SEM), transmission electron microscopy(TEM) and UV-Vis spectroscopy. The results showed that LSCOS was successfully synthesized in ionic liquid and BSA-loaded LSCOS microspheres were spherical in shape with particle size approximately 1 μm. The microspheres had a smoother surface with the increasing ratio of BSA/LSCOS and a rougher surface with the increasing ratio of glutaraldehyde/LSCOS. Decrease and increase in the ratio of BSA/LSCOS and glutaraldehyde/LSCOS, respectively, resulted in the decrease of the cumulative release of BSA. The data indicated that protein release rate can be controlled by adjusting the protein ratio and the glutaraldehyde ratio. Therefore, the LSCOS synthesized in ionic liquid could be a promising material with slow-release function for protein delivery.

Key words: Ionic liquid, Chitosan, Derivative, Emulsification cross-linking method, Microsphere

中图分类号:

O636.1

TrendMD:

刘圆圆, 黄燕, 吕正荣, BOAMAH Peter-Osei, 张岐, 吴静波, 华明清. 基于壳聚糖衍生物的蛋白质药物载体材料的制备及性能. 高等学校化学学报, 2015, 36(3): 589.

LIU Yuanyuan, HUANG Yan, LU Zhengrong, BOAMAH Peter-Osei, ZHANG Qi, WU Jingbo, HUA Mingqing. Preparation and Characterization of Chitosan Derivative Microspheres for Protein Delivery^†. Chem. J. Chinese Universities, 2015, 36(3): 589.

图/表 9

Scheme 1 Synthetic routes of LSCOS

Fig.1 1H NMR spectra of COS(a), SCOS(b) and LSCOS(c)

Fig.2 FTIR spectra of COS(a), SCOS(b) and LSCOS(c)

Fig.3 SEC spectra of standard samples with various weight-average molar mass(A) and COS(B,a),SCOS(B,b) and LSCOS(B,c) The data indicated were the retention time(t) and the weight-average molar mass(Mˉ).

Fig.4 SEM images of BSA/LSCOS microspheres with different m(BSA):m(LSCOS) m(BSA):m(LSCOS): (A) 0:100; (B) 25:100; (C) 50:100. Inset of (A): SEM image of froctured microspheres of (A).

Fig.5 SEM images of BSA/LSCOS(50:100) microspheres cross-linked with m(glutaraldehyde):m(LSCOS) of 5:100(A, B) and 10:100(C, D)

Fig.6 TEM images of LSCOS microspheres(A) for blank control and BSA/LSCOS(50:100, B) microspheres

Table 1 LC and LE of BSA/LSCOS microspheres

m(BSA):m(LSCOS)	m(Glutaraldehyde):m(LSCOS)	LC(%)	LE(%)
25:100		8.1	42
50:100		17.0	52
50:100	5:100	18.1	56
50:100	10:100	19.6	59

Fig.7 BSA accumulative release curves of non-cross-linked(a, b) and cross-linked BSA/LSCOS microspheres a. m(BSA):m(LSCOS)=25:100; b. m(BSA):m(LSCOS)=50:100; c. m(BSA):m(LSCOS)=50:100, m(Glutaraldehyde):m(LSCOS)=5:10; d. m(BSA):m(LSCOS)=50:100, m(Glutaraldehyde):m(LSCOS)=10:100.

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基于壳聚糖衍生物的蛋白质药物载体材料的制备及性能

Preparation and Characterization of Chitosan Derivative Microspheres for Protein Delivery^†

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基于壳聚糖衍生物的蛋白质药物载体材料的制备及性能

Preparation and Characterization of Chitosan Derivative Microspheres for Protein Delivery†

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Preparation and Characterization of Chitosan Derivative Microspheres for Protein Delivery^†