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载药纳米囊泡的制备、载药氧化锌纳米粒的制备及其生物学活性。

Formulation, preparation of niosome loaded zinc oxide nanoparticles and biological activities.

机构信息

Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.

Department of Microbiology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran.

出版信息

Sci Rep. 2024 Jul 19;14(1):16692. doi: 10.1038/s41598-024-67509-5.

Abstract

In this study, zinc oxide nanoparticles (Zn-NPs) were prepared by the green synthesis method and loaded inside niosomes as a drug release system and their physicochemical and biological properties were determined. Zn-NPs were prepared by the eco-friendly green strategy, the structure, and morphological properties were studied and loaded into niosomes. Subsequently, different formulations of niosomes containing Zn-NPs were prepared and the optimal formulation was used for biological studies. Scanning electron microscope (SEM) and dynamic light scattering (DLS) were used to investigate the morphology and size of nanoparticles. Fourier transform infrared spectroscopy (FTIR) and UV-Vis were used to confirm the synthesis of Zn-NPs. Energy dispersive X-ray spectrometer (EDS) determined the elemental analysis of the Zn-NPs synthesis solution and the crystalline structure of Zn-NPs was analysed by XRD (X-Ray diffraction). Furthermore, Zn-NPs were loaded inside the niosomes, and their structural characteristics, entrapment efficiency (EE%), the release profile of Zn-NPs, and their stability also were assessed. Moreover, its antimicrobial properties against some microbial pathogens, its effect on the expression of biofilm genes, and its anticancer activity on the breast cancer cell lines were also determined. To study the cytocompatibility, exposure of niosomes against normal HEK-293 cells was carried out. In addition, the impact of niosomes on the expression of genes involved in the apoptosis (Bcl2, Casp3, Casp9, Bax) at the mRNA level was measured. Our findings revealed that the Zn-NPs have a round shape and an average size of 27.60 nm. Meanwhile, UV-Vis, FTIR, and XRD results confirmed the synthesis of Zn-NPs. Also, the EE% and the size of the optimized niosomal formulation were 31.26% and 256.6 ± 12 nm, respectively. The release profile showed that within 24 h, 26% of Zn-NPs were released from niosomes, while in the same period, 99% of free Zn-NPs were released, which indicates the slow release of Zn-NPs from niosomes. Antimicrobial effects exhibited that niosomes containing Zn-NPs had more significant antimicrobial and anti-biofilm effects than Zn-NPs alone, the antimicrobial and anti-biofilm effects increased 2 to 4 times. Cytotoxic effects indicated that when Zn-NPs are loaded into niosomes, the anticancer activity increases compared to Zn-NPs alone and has low cytotoxicity on cancer cells. Niosomes containing ZnNPs increased the apoptosis-related gene expression level and reduced the Bcl2 genes. In general, the results show that niosomes can increase the biological effects of free Zn-NPs and therefore can be a suitable carrier for targeted delivery of Zn-NPs.

摘要

在这项研究中,氧化锌纳米粒子(Zn-NPs)通过绿色合成方法制备,并负载在囊泡内作为药物释放系统,测定其物理化学和生物学性质。Zn-NPs 通过环保的绿色策略制备,研究了其结构和形态特性,并将其负载在囊泡内。随后,制备了不同配方的含有 Zn-NPs 的囊泡,并选择最佳配方进行生物学研究。扫描电子显微镜(SEM)和动态光散射(DLS)用于研究纳米粒子的形态和尺寸。傅里叶变换红外光谱(FTIR)和紫外可见光谱(UV-Vis)用于确认 Zn-NPs 的合成。能量色散 X 射线光谱仪(EDS)测定 Zn-NPs 合成溶液的元素分析,X 射线衍射(XRD)分析 Zn-NPs 的晶体结构。此外,将 Zn-NPs 负载在囊泡内,评估其结构特征、包封效率(EE%)、Zn-NPs 的释放曲线及其稳定性。此外,还研究了其对一些微生物病原体的抗菌性能、对生物膜基因表达的影响以及对乳腺癌细胞系的抗癌活性。为了研究细胞相容性,对囊泡暴露于正常 HEK-293 细胞进行了研究。此外,还测量了囊泡对凋亡相关基因(Bcl2、Casp3、Casp9、Bax)mRNA 水平表达的影响。我们的研究结果表明,Zn-NPs 呈圆形,平均粒径为 27.60nm。同时,UV-Vis、FTIR 和 XRD 结果证实了 Zn-NPs 的合成。此外,优化的囊泡制剂的 EE%和粒径分别为 31.26%和 256.6±12nm。释放曲线表明,在 24 小时内,有 26%的 Zn-NPs 从囊泡中释放出来,而在同一时期,有 99%的游离 Zn-NPs 释放出来,这表明 Zn-NPs 从囊泡中的释放速度较慢。抗菌效果表明,载有 Zn-NPs 的囊泡比单独的 Zn-NPs 具有更显著的抗菌和抗生物膜效果,抗菌和抗生物膜效果增加了 2 到 4 倍。细胞毒性作用表明,当 Zn-NPs 被负载到囊泡中时,与单独的 Zn-NPs 相比,其抗癌活性增加,对癌细胞的细胞毒性较低。载有 ZnNPs 的囊泡增加了与凋亡相关的基因表达水平,并降低了 Bcl2 基因。总的来说,结果表明囊泡可以提高游离 Zn-NPs 的生物学效应,因此可以作为 Zn-NPs 靶向递送的合适载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c03/11271597/902e079f8de8/41598_2024_67509_Fig1_HTML.jpg

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