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从 PVA/LDH-和 PEG/LDH 包覆的氧化铁纳米粒子中释放肝抗癌药物索拉非尼用于药物输送应用。

Release of a liver anticancer drug, sorafenib from its PVA/LDH- and PEG/LDH-coated iron oxide nanoparticles for drug delivery applications.

机构信息

Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, Selangor, Malaysia.

Department of Linguistic and Human Sciences, Begum Nusrat Bhutto Women University, Sukkur, Sindh, 65200, Pakistan.

出版信息

Sci Rep. 2020 Dec 9;10(1):21521. doi: 10.1038/s41598-020-76504-5.

Abstract

The use of nanocarriers composed of polyethylene glycol- and polyvinyl alcohol-coated vesicles encapsulating active molecules in place of conventional chemotherapy drugs can reduce many of the chemotherapy-associated challenges because of the increased drug concentration at the diseased area in the body. The present study investigated the structure and magnetic properties of iron oxide nanoparticles in the presence of polyvinyl alcohol and polyethylene glycol as the basic surface coating agents. We used superparamagnetic iron oxide nanoparticles (FNPs) as the core and studied their effectiveness when two polymers, namely polyvinyl alcohol (PVA) and polyethylene glycol (PEG), were used as the coating agents together with magnesium-aluminum-layered double hydroxide (MLDH) as the nanocarrier. In addition, the anticancer drug sorafenib (SO), was loaded on MLDH and coated onto the surface of the nanoparticles, to best exploit this nano-drug delivery system for biomedical applications. Samples were prepared by the co-precipitation method, and the resulting formation of the nanoparticles was confirmed by X-ray, FTIR, TEM, SEM, DLS, HPLC, UV-Vis, TGA and VSM. The X-ray diffraction results indicated that all the as-synthesized samples contained highly crystalline and pure FeO. Transmission electron microscopy analysis showed that the shape of FPEGSO-MLDH nanoparticles was generally spherical, with a mean diameter of 17 nm, compared to 19 nm for FPVASO-MLDH. Fourier transform infrared spectroscopy confirmed the presence of nanocarriers with polymer-coating on the surface of iron oxide nanoparticles and the existence of loaded active drug consisting of sorafenib. Thermogravimetric analyses demonstrated the thermal stability of the nanoparticles, which displayed enhanced anticancer effect after coating. Vibrating sample magnetometer (VSM) curves of both produced samples showed superparamagnetic behavior with the high saturation magnetization of 57 emu/g for FPEGSO-MLDH and 49 emu/g for FPVASO-MLDH. The scanning electron microscopy (SEM) images showed a narrow size distribution of both final samples. The SO drug loading and the release behavior from FPEGSO-MLDH and FPVASO-MLDH were assessed by ultraviolet-visible spectroscopy. This evaluation showed around 85% drug release within 72 h, while 74% of sorafenib was released in phosphate buffer solution at pH 4.8. The release profiles of sorafenib from the two designed samples were found to be sustained according to pseudo-second-order kinetics. The cytotoxicity studies confirmed the anti-cancer activity of the coated nanoparticles loaded with SO against liver cancer cells, HepG2. Conversely, the drug delivery system was less toxic than the pure drug towards fibroblast-type 3T3 cells.

摘要

使用由聚乙二醇和聚乙烯醇包覆的囊泡组成的纳米载体来包裹活性分子,而不是使用传统的化疗药物,可以减少许多与化疗相关的挑战,因为在体内患病部位的药物浓度增加了。本研究调查了在聚乙二醇和聚乙烯醇作为基本表面涂层剂的存在下氧化铁纳米粒子的结构和磁性能。我们使用超顺磁氧化铁纳米粒子(FNPs)作为核心,并研究了当两种聚合物,即聚乙烯醇(PVA)和聚乙二醇(PEG),一起用作涂层剂时,它们与镁铝层状双氢氧化物(MLDH)作为纳米载体的有效性。此外,将抗癌药物索拉非尼(SO)负载到 MLDH 上,并涂覆在纳米粒子表面,以充分利用这种纳米药物传递系统进行生物医学应用。样品通过共沉淀法制备,通过 X 射线、FTIR、TEM、SEM、DLS、HPLC、UV-Vis、TGA 和 VSM 确认了纳米粒子的形成。X 射线衍射结果表明,所有合成的样品均包含高结晶度和纯 FeO。透射电子显微镜分析表明,FPEGSO-MLDH 纳米粒子的形状通常为球形,平均直径为 17nm,而 FPVASO-MLDH 为 19nm。傅里叶变换红外光谱证实了纳米载体的存在,其表面涂有聚合物,并且存在由索拉非尼组成的负载活性药物。热重分析证明了纳米粒子的热稳定性,经过涂层后,其显示出增强的抗癌效果。振动样品磁强计(VSM)曲线显示两种产物均表现出超顺磁性,FPEGSO-MLDH 的饱和磁化强度为 57 emu/g,FPVASO-MLDH 的饱和磁化强度为 49 emu/g。扫描电子显微镜(SEM)图像显示两个最终样品的粒径分布较窄。通过紫外可见光谱评估了 FPEGSO-MLDH 和 FPVASO-MLDH 中 SO 药物的负载和释放行为。该评估表明,在 72 小时内约有 85%的药物释放,而在 pH 值为 4.8 的磷酸盐缓冲溶液中,索拉非尼释放了 74%。发现根据拟二级动力学,索拉非尼从两种设计的样品中的释放曲线是持续的。细胞毒性研究证实了负载 SO 的包覆纳米粒子对肝癌细胞 HepG2 的抗癌活性。相反,与纯药物相比,药物输送系统对成纤维细胞型 3T3 细胞的毒性较小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dad5/7725814/6635e51944d5/41598_2020_76504_Fig1_HTML.jpg

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