负载二甲酸钾缓释抗菌微球的构建

doi:10.15541/jim20200131

无机材料学报 ›› 2021, Vol. 36 ›› Issue (2): 181-187.DOI: 10.15541/jim20200131 CSTR: 32189.14.10.15541/jim20200131

所属专题：【虚拟专辑】药物递送(2020~2021)；【虚拟专辑】抗菌材料(2020~2021)

负载二甲酸钾缓释抗菌微球的构建

郭小炜¹(), 李玉妍¹, 陈南春¹(), 王秀丽²(), 解庆林³

1.桂林理工大学材料科学与工程学院, 桂林 541004
2.桂林理工大学化学与生物工程学院, 桂林 541006
3.桂林理工大学广西岩溶地区水污染控制与用水安全保障协同创新中心, 桂林 541006

收稿日期:2020-03-12 修回日期:2020-05-20 出版日期:2021-02-20 网络出版日期:2020-06-09
通讯作者: 陈南春, 教授. E-mail: cnc@glut.edu.cn;
作者简介:郭小炜(1993-), 男, 硕士研究生. E-mail: 781860301@qq.com
基金资助:
国家自然科学基金(51564008);国家自然科学基金(41662005);广西科技攻关项目(11107003-4);广西自然科学基金(2015GXNSFAA139094);广西自然科学基金(2016GXNSFAA380014)

Construction of Sustainable Release Antimicrobial Microspheres Loaded with Potassium Diformate

GUO Xiaowei¹(), LI Yuyan¹, CHEN Nanchun¹(), WANG Xiuli²(), XIE Qinglin³

1. School of Materials Science and Engineering, Guilin University of Technology, Guilin 541004, China
2. School of Chemical and Biological Engineering, Guilin University of Technology, Guilin 541006, China
3. Guangxi Collaborative Innovation Center for Water Pollution Control and Water Safety in Karst Area, Guilin University of Technology, Guilin 541006, China

Received:2020-03-12 Revised:2020-05-20 Published:2021-02-20 Online:2020-06-09
About author:GUO Xiaowei(1993-), male, Master candidate. E-mail: 781860301@qq.com
Supported by:
National Natural Science Foundation of China(51564008);National Natural Science Foundation of China(41662005);Guangxi Science and Technology Project(11107003-4);Natural Science Foundation of Guangxi(2015GXNSFAA139094);Natural Science Foundation of Guangxi(2016GXNSFAA380014)

摘要/Abstract

摘要：

为避免二甲酸钾(KDF)在酸性环境下分解过快, 调节仔猪肠胃道酸碱性和菌落平衡, 实现KDF靶向释放抗菌, 本研究以可生物降解的壳聚糖(CS)、羧甲基纤维素(CMC)和无机刚性材料P型沸石分子筛(Zeolite P)为载体, 负载抗菌药物二甲酸钾制备控释水凝胶微球。发现CS中-NH₂与CMC中-COOH离子作用, 可形成结构稳定的聚电解质复合物。溶胀率的差异性表明CS/CMC/Zeolite P水凝胶微球对pH高度敏感。加入Zeolite P使水凝胶微球在pH1.2保持原有形貌且不被降解破裂。CS/CMC/Zeolite P/KDF抗菌微球的包封率为47.75%, 载药率为23.88%, 可有效缓释KDF, 在pH7.4磷酸盐缓冲溶液中的缓释性比pH1.2更优。CS/CMC/Zeolite P/KDF抗菌微球浓度为96 mg/mL时对大肠杆菌最大抑菌率为83%, 有效提高了KDF利用率。

关键词: 二甲酸钾, 水凝胶微球, 缓释, 抗菌

Abstract:

To prevent potassium diformate (KDF) from decomposing too quickly in an acidic environment, adjust the acidity and alkalinity of the gastrointestinal tract of the piglets and the colony balance, and realize the targeted release of KDF antibacterial, in this study, a kind of hydrogel microspheres were prepared by biodegradable chitosan (CS), carboxymethyl cellulose (CMC), and inorganic rigid material P-type molecular sieve (Zeolite P). Then the antibacterial drug potassium diformate was loaded so as to be controlled to release from this hydrogel microsphere. The results show that -NH₂ in CS and -COOH in CMC form a stable polyelectrolyte complex through ion interaction. Swelling rate test indicates that the CS/CMC/Zeolite P hydrogel microspheres display high pH-sensitivity. The addition of Zeolite P allows the hydrogel microspheres to maintain their original morphology at pH1.2 without being degraded or broken. The effective sustained-release KDF in pH7.4 phosphate buffer solution exhibits better sustained-release performance than that in pH1.2. When the concentration of CS/CMC/Zeolite P/KDF antimicrobial microspheres is 96 mg/mL, the maximum bacteriostatic rate of Escherichia coli is 83%, which effectively improves the utilization rate of KDF.

Key words: potassium diformate, hydrogel microsphere, sustained-release, antibacterial

中图分类号:

TB332

郭小炜, 李玉妍, 陈南春, 王秀丽, 解庆林. 负载二甲酸钾缓释抗菌微球的构建[J]. 无机材料学报, 2021, 36(2): 181-187.

GUO Xiaowei, LI Yuyan, CHEN Nanchun, WANG Xiuli, XIE Qinglin. Construction of Sustainable Release Antimicrobial Microspheres Loaded with Potassium Diformate[J]. Journal of Inorganic Materials, 2021, 36(2): 181-187.

图/表 10

图1 负载KDF的抗菌微球的制备过程

Fig. 1 Preparation of antibacterial microspheres loaded with KDF

图2 CMC (a)、CS (b)、Zeolite P (c)和CS/CMC/Zeolite P (d)红外光谱图

Fig. 2 FT-IR spectra of CMC (a), CS (b), Zeolite P (c) and CS/CMC/Zeolite P (d) CS: chitosan; CMC: carboxymethyl cellulose; Zeolite P: Zeolite P molecular sieve

图3 CS/CMC/Zeolite/KDF微球结构

Fig. 3 Structures of CS/CMC/Zeolite/KDF microspheres

图4 CS/CMC/Zeolite P(a)、CS/CMC(b)、CMC(c)和CS(d)的热重分析

Fig. 4 TGA analysis of CS/CMC/Zeolite P(a), CS/CMC(b), CMC(c) and CS(d) CS: chitosan; CMC: carboxymethyl cellulose; Zeolite P: Zeolite P molecular sieve

图5 CS/CMC/Zeolite P的内部SEM照片

Fig. 5 Internal SEM images of CS/CMC/Zeolite P

图6 在不同pH环境下Zeolite P添加量对CS/CMC/Zeolite P溶胀行为的影响

Fig. 6 Effect of Zeolite P concentration on swelling ratios of CS/CMC/Zeolite P in pH 7.4, pH 6.8 and pH 1.2

图7 在不同pH环境下, Zeolite P的添加量对CS/CMC/Zeolite P/KDF微球释放KDF的行为影响

Fig. 7 Effect of Zeolite P concentration on KDF release profiles of CS/CMC/Zeolite P/KDF in pH 7.4 (a) and pH 1.2 (b)

图8 CS/CMC/Zeolite P/KDF在模拟胃液中的释放动力学方程及其零级动力学拟合曲线(a),一级动力学拟合曲线(b), Higuchi方程拟合曲线(c)

Fig. 8 Kinetic equation of CS/CMC/Zeolite P/KDF in simulated gastric fluid with curves of Zero order kinetics (a),First order kinetics (b) and Higuchi equations (c)

图9 CS/CMC/Zeolite P/KDF在模拟肠道环境中的拟合曲线及其动力学方程

Fig. 9 Kinetic equation of CS/CMC/Zeolite P/KDF in simulated intestinal fluid with curves of Zero order kinetics (a),First order kinetics (b), Higuchi equations (c)

图10 抗菌液对大肠杆菌的抑菌率

Fig. 10 Antibacterial rates of antibacterial agents with different concentrations on Escherichia coli

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负载二甲酸钾缓释抗菌微球的构建

Construction of Sustainable Release Antimicrobial Microspheres Loaded with Potassium Diformate

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