利用电纺丝技术制备含有双硫仑-铜复合物的聚乙烯醇纳米纤维:一种潜在的抗黑色素瘤给药系统

IF 2.5 4区 医学 Q3 PHARMACOLOGY & PHARMACY DARU Journal of Pharmaceutical Sciences Pub Date : 2024-12-01 Epub Date: 2024-07-04 DOI:10.1007/s40199-024-00527-w
Gomaa F El Fawal, Marwa M Abu-Serie
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引用次数: 0

摘要

背景:黑色素瘤对人类健康构成严重威胁,因此开发安全有效的治疗方法是一项重大挑战。双硫仑(DS)是一种成熟的抗癌药物,与铜(DS-Cu 复合物)联合使用时显示出良好的疗效:本研究的重点是将双硫仑-铜复合物封装到聚乙烯醇(PVA)纳米纤维支架(DS-Cu@PVA)中。目的:本研究的重点是将 DS-铜复合物封装到聚乙烯醇(PVA)纳米纤维支架(DS-Cu@PVA)中,以提高黑色素瘤细胞系的生物利用度并降低其毒性:方法:使用水溶液通过电纺丝工艺制成支架,随后使用 ART-傅立叶变换红外光谱(ART-FTIR)、扫描电子显微镜(SEM)和能量色散 X 射线分析(EDX)对其进行分析。此外,还进行了细胞毒性、流式细胞仪分析和 Caspase 3 活性测定,以进一步确定支架的特性:结果:研究结果证实,通过不同的表征方法将 DS-Cu 复合物成功地封装到 PVA 中。扫描电子显微镜(SEM)分析表明,尽管添加了 DS-Cu,纳米纤维的直径仍然保持一致。此外,ATR-傅立叶变换红外光谱证实,在 PVA 中加入 DS-Cu 并没有明显改变 PVA 的特征峰。此外,利用人体正常皮肤细胞(HFB4)对 DS-Cu@PVA 纳米纤维支架进行的细胞毒性评估表明,与不含 DS-Cu 的同类产品相比,DS-Cu@PVA 纳米纤维支架具有更好的生物相容性。值得注意的是,在人和小鼠黑色素瘤细胞系(分别为 A375 和 B16F10)中,DS-Cu 的存在通过增加细胞活性氧、促凋亡基因表达和 caspase 3 活性,保持了其促进细胞凋亡的功效,同时降低了谷胱甘肽水平和癌基因表达。总之,这些研究结果表明,在 PVA 纳米纤维中添加 DS-Cu 可增强其生物相容性和对黑色素瘤细胞的细胞毒性作用,使其成为生物医学应用的理想候选材料:结论:研究结果表明,在 PVA 纳米纤维支架上靶向递送 DS-Cu 有助于提高 DS-Cu 对黑色素瘤的疗效。
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Preparation of poly(vinyl alcohol) nanofibers containing disulfiram-copper complex by electrospinning: a potential delivery system against melanoma.

Background: Melanoma poses a significant threat to human health, making the development of a safe and effective treatment a crucial challenge. Disulfiram (DS) is a proven anticancer drug that has shown effectiveness when used in combination with copper (DS-Cu complex).

Objectives: This study focuses on encapsulation of DS-copper complex into nanofiber scaffold from polyvinyl alcohol (PVA) (DS-Cu@PVA). In order to increase bioavailability towards melanoma cell lines and decrease its toxicity.

Methods: The scaffold was fabricated through an electrospinning process using an aqueous solution, and subsequently analyzed using ART-Fourier transform infrared spectroscopy (ART-FTIR), scanning electron microscopy (SEM), and energy dispersive X-ray analysis (EDX). Additionally, cellular cytotoxicity, flow cytometry analysis, and determination of caspase 3 activity were conducted to further characterize the scaffold.

Results: The results confirmed that encapsulation of DS-Cu complex into PVA was successful via different characterization. The scanning electron microscopy (SEM) analysis revealed that the diameter of the nanofibers remained consistent despite the addition of DS-Cu. Additionally, ATR-FTIR confirmed that the incorporation of DS-Cu into PVA did not significantly alter the characteristic peaks of PVA. Furthermore, the cytotoxicity assessment of the DS-Cu@PVA nanofibrous scaffold using human normal skin cells (HFB4) demonstrated its superior biocompatibility compared to DS-Cu-free counterparts. Notably, the presence of DS-Cu maintained its effectiveness in promoting apoptosis by increasing cellular reactive oxygen species, proapoptotic gene expression, and caspase 3 activity, while simultaneously reducing glutathione levels and oncogene expression in human and mouse melanoma cell lines (A375 and B16F10, respectively). Overall, these findings suggest that the addition of DS-Cu to PVA nanofibers enhances their biocompatibility and cytotoxic effects on melanoma cells, making them a promising candidate for biomedical applications.

Conclusion: The findings indicate that the targeted delivery of DS-Cu onto a PVA nanofiber scaffold holds potential approach to enhance the efficacy of DS-Cu in combating melanoma.

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DARU Journal of Pharmaceutical Sciences
DARU Journal of Pharmaceutical Sciences PHARMACOLOGY & PHARMACY-
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期刊介绍: DARU Journal of Pharmaceutical Sciences is a peer-reviewed journal published on behalf of Tehran University of Medical Sciences. The journal encompasses all fields of the pharmaceutical sciences and presents timely research on all areas of drug conception, design, manufacture, classification and assessment. The term DARU is derived from the Persian name meaning drug or medicine. This journal is a unique platform to improve the knowledge of researchers and scientists by publishing novel articles including basic and clinical investigations from members of the global scientific community in the forms of original articles, systematic or narrative reviews, meta-analyses, letters, and short communications.
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