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一种新型抗癌药物递送系统的制备与表征:茁霉多糖/聚(甲基丙烯酸)半互穿聚合物网络水凝胶

Fabrication and Characterization of a Novel Anticancer Drug Delivery System: Salecan/Poly(methacrylic acid) Semi-interpenetrating Polymer Network Hydrogel.

作者信息

Qi Xiaoliang, Wei Wei, Li Junjian, Liu Yucheng, Hu Xinyu, Zhang Jianfa, Bi Lirong, Dong Wei

机构信息

Center for Molecular Metabolism, Nanjing University of Science & Technology, Nanjing 210094, China.

The First Bethune Hospital of Jilin University, ChangChun 130000, China.

出版信息

ACS Biomater Sci Eng. 2015 Dec 14;1(12):1287-1299. doi: 10.1021/acsbiomaterials.5b00346. Epub 2015 Nov 4.

Abstract

Salecan is a novel linear extracellular polysaccharide with a linear backbone of 1-3-linked glucopyranosyl units. Salecan is suitable for preparing hydrogels for biomedical applications due to its prominent physicochemical and biological profiles. In this contribution, a variety of innovative semi-interpenetrating polymer network (semi-IPN) hydrogels consisting of Salecan and poly(methacrylic acid) (PMAA) were developed via free radical polymerization for controlled drug delivery. The successful fabrication of the semi-IPNs was verified by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and thermogravimetric (TGA) measurements. Scanning electron microscopy (SEM) and rheology analyses demonstrated that the morphological and mechanical behaviors of the resultant hydrogels were strongly affected by the contents of Salecan and cross-linker ,'-methylenebis(acrylamide) (BIS). Moreover, the swelling properties of these hydrogels were systematically investigated, and the results indicated that they exhibited pH sensitivity. The drug delivery applications of such fabricated hydrogels were further evaluated from which doxorubicin (Dox) was chosen as a model drug for in vitro release and cell viability studies. It was found that the Dox release from the Dox-loaded hydrogels was significantly accelerated when the pH of the release media decreased from 7.4 to 5.0. Toxicity assays confirmed that the blank hydrogels had negligible toxicity to normal cells, whereas the Dox-loaded hydrogels remained high in cytotoxicity for A549 and HepG2 cancer cells. All of these attributes implied that the new proposed semi-IPNs serve as potential drug delivery platforms for cancer therapy.

摘要

可得然胶是一种新型的线性细胞外多糖,其线性主链由1-3连接的吡喃葡萄糖基单元组成。由于其突出的物理化学和生物学特性,可得然胶适用于制备用于生物医学应用的水凝胶。在本研究中,通过自由基聚合反应制备了多种由可得然胶和聚甲基丙烯酸(PMAA)组成的创新型半互穿聚合物网络(semi-IPN)水凝胶,用于控制药物释放。通过傅里叶变换红外光谱(FT-IR)、X射线衍射(XRD)和热重分析(TGA)测量验证了半互穿聚合物网络的成功制备。扫描电子显微镜(SEM)和流变学分析表明,所得水凝胶的形态和力学行为受到可得然胶和交联剂N,N'-亚甲基双丙烯酰胺(BIS)含量的强烈影响。此外,系统研究了这些水凝胶的溶胀性能,结果表明它们具有pH敏感性。进一步评估了这种制备的水凝胶的药物递送应用,从中选择阿霉素(Dox)作为模型药物进行体外释放和细胞活力研究。发现当释放介质的pH从7.4降至5.0时,载药阿霉素水凝胶中阿霉素的释放显著加速。毒性试验证实,空白水凝胶对正常细胞的毒性可忽略不计,而载药阿霉素水凝胶对A549和HepG2癌细胞仍具有高细胞毒性。所有这些特性表明,新提出的半互穿聚合物网络可作为癌症治疗的潜在药物递送平台。

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