Alginate-bentonite composite decorated by chitosan-folate conjugate for the oral delivery of 5-Fluorouracil

R. Surya, Manohar D. Mullassery, Noeline B. Fernandez, D. Thomas
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Abstract

Abstract In this work, a novel alginate-modified Na-Bentonite clay composite (APTSB-AL) was synthesized via an ionotropic gelation technique for the controlled delivery of 5-Flurouracil. Characterization of the composite was performed using Fourier transform infrared spectroscopy (FTIR): X-ray diffraction (XRD): scanning electron microscopy (SEM) etc. In order to acquire the targeted drug delivery, the composite was covered by chitosan-folate conjugate (APTSB-AL-CSFA). The freeze-drying method was adopted to avoid the leakage of water-soluble drug molecules during the drying process. The maximum swelling of the composite was found to be at pH 6.8 and the maximum drug release was at pH 7.4. The release kinetics mechanism was explained by the Korsmeyer-Peppas kinetic model. In order to find out the material toxicity, the biocompatibility assay in a normal cell line of mouse fibroblast (L929) was carried out. At the concentration of 2.5 μg/ml, the cell toxicity was negligible. At the high concentration level of 40.0 μg/ml, the cell viability was not less than 70.0 %. The in vitro cytotoxicity of the drug-loaded composite was studied in Human Colorectal Adenocarcinoma cells and the findings indicated good biocompatibility of the composite. At the concentration of 2.5 μg/ml of the drug-loaded composite (FU-L-APTSB-AL-CSFA): the cell toxicity was found to be less than 50%. And at the high concentration level of 40.0 μg/ml, the cell viability was found to be less than 10%, indicating the targeting action of the loaded composite. GRAPHICAL ABSTRACT
壳聚糖-叶酸共轭物装饰的藻酸盐-膨润土复合材料用于 5-氟尿嘧啶的口服给药
摘要 本研究通过离子凝胶技术合成了一种新型海藻酸盐修饰的 Na-Bentonite 粘土复合材料(APTSB-AL),用于 5-氟尿嘧啶的控制给药。利用傅立叶变换红外光谱(FTIR)对该复合材料进行了表征:X 射线衍射(XRD)、扫描电子显微镜(SEM)等。为了实现靶向给药,复合材料被壳聚糖-叶酸共轭物(APTSB-AL-CSFA)覆盖。为了避免水溶性药物分子在干燥过程中泄漏,采用了冷冻干燥法。结果发现,在 pH 值为 6.8 时,复合材料的溶胀度最大,而在 pH 值为 7.4 时,药物释放量最大。释放动力学机制由 Korsmeyer-Peppas 动力学模型解释。为了了解材料的毒性,在小鼠成纤维细胞(L929)的正常细胞系中进行了生物相容性试验。浓度为 2.5 μg/ml 时,细胞毒性可忽略不计。在 40.0 μg/ml 的高浓度水平下,细胞存活率不低于 70.0%。在人大肠腺癌细胞中研究了载药复合材料的体外细胞毒性,结果表明复合材料具有良好的生物相容性。当药物负载复合材料(FU-L-APTSB-AL-CSFA)的浓度为 2.5 μg/ml 时,细胞毒性低于 50%。而在 40.0 μg/ml 的高浓度水平下,细胞存活率低于 10%,这表明负载复合材料具有靶向作用。图表摘要
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CiteScore
2.30
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