Uspenskaya Elena V, Syroeshkin Anton V, Pleteneva Tatiana V, Kazimova Ilaha V, Grebennikova Tatiana V, Fedyakina Irina T, Lebedeva Varvara V, Latyshev Oleg E, Eliseeva Olesia V, Larichev Viktor F, Garaev Timur M, Maximova Tatiana V, Morozova Mariya A, Hanh Pham My
Department of Pharmaceutical and Toxicological Chemistry, Medical Institute, RUDN University, 6 Miklukho-Maklaya Street, 117198 Moscow, Russia.
National Research Center for Epidemiology and Microbiology Named after the Honorary Academician N. F. Gamaleya, 18 Gamaleya St., 123098 Moscow, Russia.
Pharmaceutics. 2021 Nov 18;13(11):1954. doi: 10.3390/pharmaceutics13111954.
Natural polyelectrolytes, including in the form of complexes with colloidal particles, are increasingly used in pharmacy due to the possibility of regulated attachment of medicinal substances and their targeted delivery to the target organ. However, the formation, stability, and molecular-mass characteristics of polyelectrolyte nanodispersions (ND) vary depending on the nature and composition of the medium of their origin. This is due to the lack of standardized approaches to quality control and regulatory documentation for most natural ND. In this paper, we first introduced the isolation, followed by investigations into their physico-chemical properties and bioactivity. Using the dried droplet method, we were able to detect the "coffee ring effect". Fractographic studies of the surface structure of EHA and FA dried samples using SEM showed its heterogeneity and the presence of submicron particles encapsulated in the internal molecular cavities of polyelectrolyte. FTIR spectroscopy revealed the ND chemical structure of benzo-α-pyron and benzo-γ-pyron, consisting of nanoparticles and a branched frame part. The main elements detected by X-ray fluorescence in humic substance extract and fulvic acid include Si, P, S, K, Ca, Mn, Fe, Cu, Zn, whereas Fe is in high concentrations. The UV-spectra and fluorescent radiation demonstrated the possibility of studying the effect of the fulvate chromone structure on its optical properties. It is shown that dilution of the initial solutions of polyelectrolytes 1:10 contributes to the detection of smaller nanoparticles and an increase in the absolute value of the negative ζ-potential as a factor of ND stability. A study of the EHS effect on the SARS-CoV-2 virus infectious titer in the Vero E6 cell showed the effective against virus both in the virucidal scheme (the SI is 11.90-22.43) and treatment/prevention scheme (the SI is 34.85-57.33). We assume that polyelectrolyte ND prevent the binding of the coronavirus spike glycoprotein to the receptor. Taking into account the results obtained, we expect that the developed approach can become unified for the standardization of the ND natural polyelectrolytes complex, which has great prospects for use in pharmacy and medicine as a drug with antiviral activity.
天然聚电解质，包括与胶体颗粒形成复合物的形式，由于其能够调控药物的附着并将其靶向递送至靶器官，在药学领域的应用越来越广泛。然而，聚电解质纳米分散体（ND）的形成、稳定性和分子量特性会因其起源介质的性质和组成而有所不同。这是因为大多数天然ND缺乏质量控制和监管文件的标准化方法。在本文中，我们首先介绍了其分离方法，随后对其物理化学性质和生物活性进行了研究。使用干燥液滴法，我们能够检测到“咖啡环效应”。利用扫描电子显微镜（SEM）对EHA和FA干燥样品的表面结构进行的断口分析表明其具有异质性，并且在聚电解质的内分子腔中存在包裹的亚微米颗粒。傅里叶变换红外光谱（FTIR）揭示了苯并-α-吡喃酮和苯并-γ-吡喃酮的ND化学结构，其由纳米颗粒和分支框架部分组成。通过X射线荧光在腐殖质提取物和富里酸中检测到的主要元素包括硅、磷、硫、钾、钙、锰、铁、铜、锌，其中铁的浓度较高。紫外光谱和荧光辐射证明了研究富马酸盐色酮结构对其光学性质影响的可能性。结果表明，将聚电解质初始溶液按1:10稀释有助于检测到更小的纳米颗粒，并增加负ζ电位的绝对值，这是ND稳定性的一个因素。对EHS对Vero E6细胞中SARS-CoV-2病毒感染滴度的影响进行的研究表明，其在杀病毒方案（SI为11.90 - 22.43）和治疗/预防方案（SI为34.85 - 57.33）中均对病毒有效。我们假设聚电解质ND可防止冠状病毒刺突糖蛋白与受体结合。考虑到所获得的结果，我们期望所开发的方法能够成为用于ND天然聚电解质复合物标准化的统一方法，其作为具有抗病毒活性的药物在药学和医学领域具有广阔的应用前景。
