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基于结冷胶的水凝胶的合成与表征及其用于抗癌药物依托泊苷的递送。

Synthesis and characterization of Gellan gum-based hydrogels for the delivery of anticancer drug etoposide.

机构信息

Department of Paramedical Sciences, St. Soldier Institute of Pharmacy, Jalandhar, Punjab, India.

Department of Applied Sciences, CT Institute of Engineering, Management and Technology, Shahpur Campus Jalandhar, Punjab, India.

出版信息

Int J Biol Macromol. 2024 Oct;278(Pt 3):135007. doi: 10.1016/j.ijbiomac.2024.135007. Epub 2024 Aug 22.

DOI:10.1016/j.ijbiomac.2024.135007
PMID:39181355
Abstract

Present research work reports the synthesis of Gellan gum (Gg) and methacrylic acid (MA) based grafted hydrogels (Gg-cl-poly(MA)) crosslinked using N, N'- methylene-bis-acrylamide (MBA) and the evaluation of their efficiency to be used as a sustained drug delivery carrier for anticancer drug i.e., etoposide. Various characterization techniques like Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM) confirmed the grafting of Gg with MA and the formation of crosslinked Gg-cl-poly(MA) hydrogel polymer. The synthesized hydrogel showed pH-dependent swelling properties and exhibited a maximum swelling capacity of 867 % under optimized environmental conditions. The Gg-cl-poly(MA) was biocompatible and non-cytotoxic, which was confirmed by the hemolytic and cytotoxic tests. The release dynamics of etoposide from the Gg-cl-poly(MA) polymer matrix was checked under specific physiological conditions. Drug release was found to be significantly higher in the acidic medium, followed by the neutral and alkaline medium. This clearly indicated that etoposide drug release through synthesized hydrogel was stomach-specific and it is effective for the treatment of stomach cancer. The release mechanism of the etoposide drug was a Fickian-type diffusion mechanism in the acidic medium and a non-Fickian-type diffusion mechanism in the neutral and alkaline medium. The release profile of the etoposide was best fitted to the first-order rate model. The results showed that the synthesized hydrogel (i.e., Gg-cl-poly(MA)) was biocompatible, non-toxic, and could be used for the treatment of stomach cancer.

摘要

目前的研究工作报告了用 N, N'-亚甲基双丙烯酰胺 (MBA) 交联的结冷胶 (Gg) 和甲基丙烯酸 (MA) 接枝水凝胶 (Gg-cl-poly(MA)) 的合成及其作为抗癌药物依托泊苷的缓释药物载体的效率评价。傅里叶变换红外光谱 (FTIR)、X 射线衍射 (XRD) 和扫描电子显微镜 (SEM) 等各种表征技术证实了 Gg 与 MA 的接枝以及交联 Gg-cl-poly(MA)水凝胶聚合物的形成。合成的水凝胶表现出 pH 依赖性溶胀特性,在优化的环境条件下具有 867%的最大溶胀能力。Gg-cl-poly(MA)具有良好的生物相容性和非细胞毒性,这通过溶血和细胞毒性试验得到了证实。在特定的生理条件下检查了依托泊苷从 Gg-cl-poly(MA)聚合物基质中的释放动力学。在酸性介质中,药物释放明显更高,其次是中性和碱性介质。这清楚地表明,通过合成水凝胶释放依托泊苷是针对胃部的,对胃癌的治疗有效。依托泊苷药物的释放机制在酸性介质中是菲克扩散机制,在中性和碱性介质中是非菲克扩散机制。依托泊苷的释放曲线最符合一级速率模型。结果表明,合成水凝胶 (即 Gg-cl-poly(MA)) 具有良好的生物相容性、无毒性,可用于治疗胃癌。

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