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血浆介导的二甲双胍固定在聚乙烯上:对药物释放、抗菌活性和生物相容性的影响。

Plasma mediated immobilization of metformin on polyethylene: effects on drug release, antibacterial activity, and biocompatibility.

作者信息

Žídek Štěpán, Štěpánková Kateřina, Pištěková Hana, Masař Milan, Stupavská Monika, Sťahel Pavel, Trunec David, Mozetič Miran, Valasek Pavel, Lehocky Marian

机构信息

Centre of Polymer Systems, University Institute, Tomas Bata University in Zlín, Zlin, Czech Republic.

Department of Plasma Physics and Technology, Faculty of Science, Masaryk University, Brno, Czech Republic.

出版信息

J Biomater Sci Polym Ed. 2025 Jul 3:1-23. doi: 10.1080/09205063.2025.2524261.

DOI:10.1080/09205063.2025.2524261
PMID:40608963
Abstract

Metformin, a widely used antidiabetic drug, has gained attention for its potential applications in antimicrobial surfaces, delivery systems, and anticancer therapy. However, immobilizing metformin in a stable, bioactive, and dose-controllable manner onto a chemically inert, hydrophobic surface is challenging. The objective of this study is to immobilize metformin at various concentration (0.5, 1, 2, 5, 10, and 20 g·L) onto low-density polyethylene (LDPE) surfaces by a multistep approach with the aim of creating bioactive coatings. In this approach, LDPE was first treated with a 40 kHz low pressure plasma discharge in air atmosphere, followed by non-covalent attachment of acrylic acid a grafting technique. Metformin was covalently attached to the surface N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and -Hydroxysuccinimide (NHS) activation, while its presence on the polymer surface was confirmed by Water contact angle (WCA), Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Sustained metformin release with a shift from Fickian to first-order kinetics was observed at higher drug loading. Antibacterial testing against and showed no antibacterial effect at the selected concentration levels. Cytocompatibility assays with multipotent mesenchymal cells showed good biocompatibility of modified surfaces, with only dose-dependent cytotoxicity at higher metformin concentrations (>5 g·L). These results demonstrate that despite the absence of antibacterial effects, the developed system offers a promising platform for further biomedical applications requiring controlled drug surface functionalization and retained cytocompatibility.

摘要

二甲双胍是一种广泛使用的抗糖尿病药物,因其在抗菌表面、递送系统和抗癌治疗中的潜在应用而受到关注。然而,以稳定、生物活性和剂量可控的方式将二甲双胍固定在化学惰性的疏水表面上具有挑战性。本研究的目的是通过多步方法将不同浓度(0.5、1、2、5、10和20 g·L)的二甲双胍固定在低密度聚乙烯(LDPE)表面上,以制备生物活性涂层。在该方法中,首先在空气气氛中用40 kHz的低压等离子体放电处理LDPE,然后采用丙烯酸的非共价连接——一种接枝技术。通过N-(3-二甲氨基丙基)-N'-乙基碳二亚胺盐酸盐(EDC)和N-羟基琥珀酰亚胺(NHS)活化,将二甲双胍共价连接到表面,同时通过水接触角(WCA)、傅里叶变换红外光谱(FTIR)、X射线光电子能谱(XPS)和扫描电子显微镜(SEM)确认其在聚合物表面的存在。在较高药物负载量下观察到二甲双胍的持续释放,释放动力学从菲克扩散转变为一级动力学。针对金黄色葡萄球菌和大肠杆菌的抗菌测试表明,在选定的浓度水平下没有抗菌效果。与多能间充质细胞的细胞相容性测定表明改性表面具有良好的生物相容性,仅在较高的二甲双胍浓度(>5 g·L)下具有剂量依赖性细胞毒性。这些结果表明,尽管没有抗菌作用,但所开发的系统为进一步的生物医学应用提供了一个有前景的平台,该应用需要可控的药物表面功能化并保留细胞相容性。

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