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冷等离体体制备聚己内酯溶液用于静电纺丝前处理:一种提高槲皮素载药纳米纤维给药系统的新方法。

Cold atmospheric plasma modified polycaprolactone solution prior to electrospinning: A novel approach for improving quercetin-loaded nanofiber drug delivery systems.

机构信息

Department of Chemistry, Faculty of Engineering and Natural Sciences, Suleyman Demirel University, 32220 Isparta, Turkey.

出版信息

Int J Pharm. 2024 Feb 15;651:123789. doi: 10.1016/j.ijpharm.2024.123789. Epub 2024 Jan 6.

Abstract

In this study, we present a novel approach for enhancing the performance of Quercetin-loaded nanofiber drug delivery systems through the modification of Polycaprolactone (PCL) solution using Cold Atmospheric Plasma (CAP) prior to electrospinning. CAP treatment was applied to PCL solutions for varying durations, namely, 0.5, 1, and 3 min. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) collectively demonstrate that CAP application and QU loading induce morphological changes in nanofibers, facilitating the creation of drug delivery systems with modified fiber diameters, devoid of bead formation. CAP treatment duration correlates with varying fiber diameters, with the longest treatment (3 min) producing the largest fibers (1324 ± 387 nm). Concurrently, the incorporation of quercetin (QU) into the PCL nanofibers resulted in reduced fiber diameter. These observations emphasize the pivotal role of CAP modification in tailoring nanofiber size and morphology. Notably, minimal peak shifts indicate no significant molecular structure changes in PCL nanofibers compared to PCL solutions, assuring the absence of unwanted chemical modifications or degradation during electrospinning. Furthermore, specific QU peaks are undetectable in Fourier-transform infrared (FTIR) spectra, suggesting dispersed or amorphous QU molecules within the nanofibers. Additionally, X-ray diffraction (XRD) results demonstrate that CAP treatment does not alter the crystalline structure of the PCL nanofiber drug delivery system. Crystalline planes of PCL remain unchanged, affirming stability under CAP treatment conditions. Water contact angles indicate that CAP treatment affects nanofiber hydrophobicity, with shorter CAP treatment times rendering more hydrophilic surfaces. Cumulative QU release percentages vary, with PCL/CAP-0.5-QU exhibiting the highest release at 56 ± 2.2 %, surpassing unmodified PCL/QU. Moreover, cell viability remains comparable or slightly increased when QU is incorporated into CAP-treated PCL nanofibers, suggesting potential mitigation of cytotoxic effects induced by CAP treatment. The combination of QU and CAP treatment enhances cancer cell viability reduction, QU release from nanofibers, and drug loading efficiency in a synergistic manner.

摘要

在这项研究中,我们提出了一种通过在静电纺丝前使用冷等离体(CAP)对聚己内酯(PCL)溶液进行改性来增强槲皮素负载纳米纤维药物传递系统性能的新方法。对 PCL 溶液进行了不同时间的 CAP 处理,分别为 0.5、1 和 3 分钟。扫描电子显微镜(SEM)和原子力显微镜(AFM)共同表明,CAP 应用和 QU 负载会引起纳米纤维的形态变化,有助于制造具有改性纤维直径的药物传递系统,而没有珠形成。CAP 处理时间与不同的纤维直径相关,最长的处理时间(3 分钟)产生最大的纤维(1324±387nm)。同时,将槲皮素(QU)掺入 PCL 纳米纤维中会导致纤维直径减小。这些观察结果强调了 CAP 改性在调整纳米纤维尺寸和形态方面的关键作用。值得注意的是,与 PCL 溶液相比,PCL 纳米纤维的最小峰值位移表明没有明显的分子结构变化,这确保了在静电纺丝过程中没有不必要的化学修饰或降解。此外,傅里叶变换红外(FTIR)光谱中无法检测到特定的 QU 峰,这表明 QU 分子在纳米纤维中呈分散或无定形状态。此外,X 射线衍射(XRD)结果表明,CAP 处理不会改变 PCL 纳米纤维药物传递系统的结晶结构。PCL 的结晶平面保持不变,在 CAP 处理条件下保持稳定。水接触角表明 CAP 处理会影响纳米纤维的疏水性,较短的 CAP 处理时间会使表面更亲水。QU 的累积释放百分比不同,PCL/CAP-0.5-QU 表现出最高的释放率为 56±2.2%,超过了未改性的 PCL/QU。此外,当 QU 掺入 CAP 处理的 PCL 纳米纤维中时,细胞活力保持相当或略有增加,这表明 CAP 处理引起的细胞毒性作用可能得到缓解。QU 和 CAP 处理的组合以协同方式增强了癌细胞活力的降低、纳米纤维中 QU 的释放以及药物负载效率。

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