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pH 响应性黏液和甲氨蝶呤给药：体外抗肿瘤和体内毒性评价。

pH Responsive Mucilage and Administration of Methotrexate: In-Vitro Antitumor and In-Vivo Toxicity Evaluation.

机构信息

Institute of Chemistry, University of Sargodha, Sargodha 40100, Pakistan.

Department of Chemistry, Sargodha Campus, The University of Lahore, Sargodha 40100, Pakistan.

出版信息

Int J Mol Sci. 2022 Mar 1;23(5):2725. doi: 10.3390/ijms23052725.

DOI:10.3390/ijms23052725
PMID:35269867
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8910941/
Abstract

The rapid progression in biomaterial nanotechnology apprehends the potential of non-toxic and potent polysaccharide delivery modules to overcome oral chemotherapeutic challenges. The present study is aimed to design, fabricate and characterize polysaccharide nanoparticles for methotrexate (MTX) delivery. The nanoparticles (NPs) were prepared by mucilage (AEM) and chitosan (CS) by the modified coacervation method, followed by ultra-sonification. The NPs showed much better pharmaceutical properties with a spherical shape and smooth surface of 213.4-254.2 nm with PDI ranging between 0.279-0.485 size with entrapment efficiency varying from 42.08 ± 1.2 to 72.23 ± 2.0. The results revealed NPs to possess positive zeta potential and a low polydispersity index (PDI). The in-vitro drug release showed a sustained release of the drug up to 32 h with pH-dependence. Blank AEM -CS NPs showed no in-vivo toxicity for a time duration of 14 days, accompanied by high cytotoxic effects of optimized MTX loaded NPs against MCF-7 and MD-MBA231 cells by MTT assay. In conclusion, the findings advocated the therapeutic potential of AEM/CS NPs as an efficacious tool, offering a new perspective for pH-responsive routing of anticancer drugs with tumor cells as a target.

摘要

生物材料纳米技术的快速发展预示着无毒且有效的多糖递药模块有潜力克服口服化疗的挑战。本研究旨在设计、制备和表征用于甲氨蝶呤（MTX）递送的多糖纳米粒。通过改良凝聚法，由刺梧桐胶（AEM）和壳聚糖（CS）制备纳米粒（NPs），然后进行超声处理。NPs 呈球形，表面光滑，平均粒径为 213.4-254.2nm，PDI 为 0.279-0.485，包封效率为 42.08±1.2%至 72.23±2.0%。结果表明 NPs 具有正的 Zeta 电位和低的多分散指数（PDI）。体外药物释放显示药物可在 32 小时内持续释放，具有 pH 依赖性。空白 AEM-CS NPs 在 14 天内无体内毒性，同时优化的载 MTX NPs 通过 MTT 测定对 MCF-7 和 MD-MBA231 细胞具有高细胞毒性。总之，这些发现表明 AEM/CS NPs 具有治疗潜力，为以肿瘤细胞为靶点的 pH 响应型抗癌药物输送提供了新的视角。

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