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用于抗菌化合物控释的木糖醇改性甲基丙烯酸缩水甘油酯-甲基丙烯酸乙酯基质的形成与表征

Formation and Characterization of Xylitol-Modified Glycidyl Methacrylate--Ethyl Methacrylate Matrices for Controlled Release of Antimicrobial Compounds.

作者信息

Chyzy Adam, Gnatowski Przemysław, Piłat Edyta, Sienkiewicz Maciej, Wozniak Katarzyna, Wojnicka Marta, Brzezinski Krzysztof, Plonska-Brzezinska Marta E

机构信息

Department of Organic Chemistry, Faculty of Medicine with the Division of Dentistry and Division of Medical Education in English, Medical University of Bialystok, Mickiewicza 2A, 15-222 Bialystok, Poland.

Department of Environmental Toxicology, Faculty of Health Sciences, Medical University of Gdańsk, Dębowa 23A, 80-204 Gdansk, Poland.

出版信息

Molecules. 2025 Jul 23;30(15):3083. doi: 10.3390/molecules30153083.

Abstract

Wounds are undeniably important gateways for pathogens to enter the body. In addition to their detrimental local effects, they can also cause adverse systemic effects. For this reason, developing methods for eradicating pathogens from wounds is a challenging medical issue. Polymers, particularly hydrogels, are one of the more essential materials for designing novel drug-delivery systems, thanks to the ease of tuning their structures. This work exploits this property by utilizing copolymerization, microwave modification, and drug-loading processes to obtain antibacterial gels. Synthesized xylitol-modified glycidyl methacrylate--ethyl methacrylate ([P(EMA)--(GMA)]-Xyl]) matrices were loaded with bacitracin, gentian violet, furazidine, and brilliant green, used as active pharmaceutical ingredients (APIs). The hydrophilic properties, API release mechanism, and antibacterial properties of the obtained hydrogels against , , and containing [P(EMA)--(GMA)]-Xyl] were studied. The hydrogels with the APIs efficiently inhibit bacteria growth with low doses of drugs, and our findings are statistically significant, confirmed with ANOVA analysis at = 0.05. The results confirmed that the proposed system is hydrophilic and has extended the drug-release capabilities of APIs with a controlled burst effect based on [P(EMA)--(GMA)]-Xyl] content in the hydrogel. Hydrogels are characterized by the prolonged release of APIs in a very short time (a few minutes). Although the amount of released APIs is about 10%, it still exceeds the minimum inhibitory concentrations of drugs. Several kinetic models (first-order, second-order, Baker-Lonsdale, and Korsmeyer-Peppas) were applied to fit the API release data from the [P(EMA)--(GMA)]-Xyl-based hydrogel. The best fit of the Korsmeyer-Peppas kinetic model to the experimental data was determined, and it was confirmed that a diffusion-controlled release mechanism of the APIs from the studied hydrogels is dominant, which is desirable for applications requiring a consistent, controlled release of therapeutic agents. A statistical analysis of API release using Linear Mixed Model was performed, examining the relationship between % mass of API, sample (hydrogels and control), time, sample-time interaction, and variability between individuals. The model fits the data well, as evidenced by the determination coefficients close to 1. The analyzed interactions in the data are reliable and statistically significant ( < 0.001). The outcome of this study suggests that the presented acrylate-based gel is a promising candidate for developing wound dressings.

摘要

伤口无疑是病原体进入人体的重要通道。除了其有害的局部影响外,它们还会引起不良的全身影响。因此,开发从伤口根除病原体的方法是一个具有挑战性的医学问题。聚合物,特别是水凝胶,由于其结构易于调节,是设计新型药物递送系统的重要材料之一。这项工作通过利用共聚、微波改性和药物负载过程来获得抗菌凝胶,从而利用了这一特性。合成的木糖醇改性甲基丙烯酸缩水甘油酯-甲基丙烯酸乙酯([P(EMA)-(GMA)]-Xyl])基质负载了杆菌肽、龙胆紫、呋喃西林和亮绿,用作活性药物成分(API)。研究了所得水凝胶对含有[P(EMA)-(GMA)]-Xyl]的金黄色葡萄球菌、大肠杆菌和铜绿假单胞菌的亲水性、API释放机制和抗菌性能。含有API的水凝胶用低剂量药物就能有效抑制细菌生长,我们的研究结果具有统计学意义,在α = 0.05时通过方差分析得到证实。结果证实,所提出的系统具有亲水性,并根据水凝胶中[P(EMA)-(GMA)]-Xyl]的含量,通过可控的突释效应扩展了API的药物释放能力。水凝胶的特点是在很短的时间(几分钟)内API能持续释放。虽然释放的API量约为10%,但仍超过药物的最低抑菌浓度。应用了几种动力学模型(一级、二级、贝克-朗斯代尔和科尔斯梅耶-佩帕斯)来拟合基于[P(EMA)-(GMA)]-Xyl]的水凝胶的API释放数据。确定了科尔斯梅耶-佩帕斯动力学模型与实验数据的最佳拟合,并证实了所研究水凝胶中API的扩散控制释放机制占主导地位,这对于需要一致、可控释放治疗剂的应用是理想的。使用线性混合模型对API释放进行了统计分析,研究了API质量百分比、样品(水凝胶和对照)、时间、样品-时间相互作用以及个体间变异性之间的关系。该模型对数据拟合良好,决定系数接近1证明了这一点。数据中分析的相互作用是可靠的且具有统计学意义(P < 0.001)。这项研究的结果表明,所呈现的丙烯酸酯基凝胶是开发伤口敷料的一个有前途的候选材料。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a327/12348667/cfc45deacf49/molecules-30-03083-g001.jpg

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