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负载槲皮苷的环糊精基纳米海绵作为治疗肺癌和新冠肺炎的一种有前景的方法。

Quercitrin loaded cyclodextrin based nanosponge as a promising approach for management of lung cancer and COVID-19.

作者信息

Abou Taleb Sally, Moatasim Yassmin, GabAllah Mohamed, Asfour Marwa Hasanein

机构信息

Pharmaceutical Technology Department, National Research Centre, El-Buhouth Street, Dokki, Cairo, 12622, Egypt.

Center of Scientific Excellence for Influenza Viruses, National Research Centre, El-Buhouth Street, Dokki, Cairo, 12622, Egypt.

出版信息

J Drug Deliv Sci Technol. 2022 Nov;77:103921. doi: 10.1016/j.jddst.2022.103921. Epub 2022 Oct 28.

Abstract

Lung cancer and pandemic acute respiratory disease, COVID-19, are examples of the most worldwide widespread diseases. The aim of the current study is to develop cyclodextrin based nanosponge (CD-NS) for loading the flavonoid drug, quercitrin (QCT). This is to improve its solubility in an attempt to enhance its activity against lung cancer as well as SARS-CoV-2 virus responsible for COVID-19. Preparation of CD-NS was performed by ultrasound-assisted synthesis method. Two CDs were employed, namely, β cyclodextrin (βCD) and 2-hydroxy propyl-β-cyclodextrin (2-HPβCD) that were crosslinked with diphenyl carbonate, one at a time. QCT loaded CD-NS revealed entrapment efficiency and particle size ranged between 94.17 and 99.03% and 97.10-325.90 nm, respectively. QCT loaded 2-HPβCD-NS revealed smaller particle size compared with that of QCT loaded βCD-NS. Zeta potential absolute values of the prepared formulations were >20 mV, indicating physically stable nanosystems. The selected formulations were investigated by Fourier transform infrared spectroscopy, X-ray powder diffraction and scanning electron microscopy which proved the formation of QCT loaded CD-NS exhibiting porous structure. QCT exhibited partial and complete amorphization in βCD-NS and 2-HPβCD-NS, respectively. release revealed an improved release of QCT from CD-NS formulations. The biological activity of free QCT and QCT loaded CD-NS was investigated against lung cancer cell line A549 as well as SARS-CoV-2 virus. The results revealed that IC values of free QCT against lung cancer cell line A549 and SARS-CoV-2 were higher than those exhibited by QCT loaded CD-NS by 1.57-5.35 and 5.95-26.95 folds, respectively. QCT loaded 2-HPβCD-NS revealed enhanced release and superior biological activity compared with QCT loaded βCD-NS.

摘要

肺癌和大流行急性呼吸道疾病COVID-19是全球范围内传播最广的疾病实例。本研究的目的是开发基于环糊精的纳米海绵(CD-NS)来负载类黄酮药物槲皮苷(QCT)。这是为了提高其溶解度,以增强其对肺癌以及导致COVID-19的SARS-CoV-2病毒的活性。CD-NS的制备采用超声辅助合成法。使用了两种环糊精,即β-环糊精(βCD)和2-羟丙基-β-环糊精(2-HPβCD),每次分别与碳酸二苯酯交联。负载QCT的CD-NS的包封率和粒径分别在94.17%至99.03%和97.10至325.90纳米之间。与负载QCT的βCD-NS相比,负载QCT的2-HPβCD-NS显示出更小的粒径。所制备制剂的ζ电位绝对值>20 mV,表明纳米系统物理稳定。通过傅里叶变换红外光谱、X射线粉末衍射和扫描电子显微镜对所选制剂进行了研究,证明了负载QCT的CD-NS形成了多孔结构。QCT在βCD-NS和2-HPβCD-NS中分别表现出部分和完全非晶化。释放显示QCT从CD-NS制剂中的释放有所改善。研究了游离QCT和负载QCT的CD-NS对肺癌细胞系A549以及SARS-CoV-2病毒的生物活性。结果显示,游离QCT对肺癌细胞系A549和SARS-CoV-2的IC值分别比负载QCT的CD-NS高1.57至5.35倍和5.95至26.95倍。与负载QCT的βCD-NS相比,负载QCT的2-HPβCD-NS显示出增强的释放和优异的生物活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a19/9616482/945f7af24332/ga1_lrg.jpg

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