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制备并表征了作为潜在药物载体的羧甲基纤维素接枝季铵化壳聚糖。

Preparation and characterization of carboxymethyl cellulose containing quaternized chitosan for potential drug carrier.

机构信息

Nanjing Forestry Univ, Coll Chem Engn, Nanjing 210037, Jiangsu, PR China; Jiangsu Key Lab Chem & Utilizat Agr & Forest Biom, Jiangsu, PR China.

Nanjing Forestry Univ, Coll Chem Engn, Nanjing 210037, Jiangsu, PR China.

出版信息

Int J Biol Macromol. 2020 Jul 1;154:1392-1399. doi: 10.1016/j.ijbiomac.2019.11.019. Epub 2019 Nov 12.

DOI:10.1016/j.ijbiomac.2019.11.019
PMID:31730962
Abstract

The objective of this study was to synthesize and characterize cystamine dihydrochloride (CYS) crosslinked carboxymethyl cellulose/quaternized chitosan (CMC/HACC) composite hydrogel film. Firstly, the glycidyl-based quaternary ammonium chitosan derivative (HACC) was synthesized using nucleophilic substitution reaction. Then HACC was analyzed by FTIR, HNMR spectra and the composite films at different blending ratio of CMC and HACC were studied by rheology measurement, mechanical and swelling tests. When the composite films were prepared under optimized conditions (CMC: HACC = 7:1), they showed excellent mechanical properties (with improved 93.3% tensile strength and 2.3% elongation at break) and swellability (equilibrium swelling ratio increased 270%) compared to pure CMC film. 5-Fluorouracil (5-FU) was used as drug model which has broad-spectrum anticancer properties. The 5-FU/CMC/HACC composite films showed redox and pH responsive of drug release properties along with well biocompatibility. The in vitro cytotoxicity and cell apoptosis studies showed the drug loaded composite films with obvious toxicity against HepG2 cells especially in the presence of GSH. In addition, CMC/HACC composite films showed good antibacterial against S. aureus and E. coli, while pure CMC film had no antimicrobial activities. It can be concluded that CMC/HACC composite films can be potentially used as targeted drug delivery system.

摘要

本研究旨在合成并表征胱胺二盐酸盐(CYS)交联羧甲基纤维素/季铵化壳聚糖(CMC/HACC)复合水凝胶膜。首先,通过亲核取代反应合成了基于缩水甘油基的季铵化壳聚糖衍生物(HACC)。然后通过傅里叶变换红外光谱(FTIR)、核磁共振谱(HNMR)对 HACC 进行了分析,并通过流变学测量、机械性能和溶胀测试研究了不同 CMC 和 HACC 共混比的复合膜。当在优化条件下(CMC:HACC=7:1)制备复合膜时,与纯 CMC 膜相比,其具有出色的机械性能(拉伸强度提高了 93.3%,断裂伸长率提高了 2.3%)和溶胀性(平衡溶胀比增加了 270%)。5-氟尿嘧啶(5-FU)被用作具有广谱抗癌特性的药物模型。5-FU/CMC/HACC 复合膜表现出氧化还原和 pH 响应的药物释放特性,同时具有良好的生物相容性。体外细胞毒性和细胞凋亡研究表明,载药复合膜对 HepG2 细胞具有明显的毒性,尤其是在存在 GSH 的情况下。此外,CMC/HACC 复合膜对金黄色葡萄球菌和大肠杆菌具有良好的抗菌活性,而纯 CMC 膜则没有抗菌活性。综上所述,CMC/HACC 复合膜可作为靶向药物传递系统。

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