Nanodispersions of Polyelectrolytes Based on Humic Substances: Isolation, Physico-Chemical Characterization and Evaluation of Biological Activity

Abstract

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.

In Vitro Determination of Inhibitory Effects of Humic Substances Complexing Zn and Se on SARS-CoV-2 Virus Replication

“…Other studies in the literature have also used HS or FA as therapeutic element carrying agents in cell culture against SARS-CoV-2. Uspenskaya et al found that the half maximal inhibitory concentration (IC 50 ) of natural HS is 0.023–0.041 mg/mL during the treatment of Vero E6 cell culture against SARS-CoV-2 virus [ 57 ]. Köntös discovered that 200 μg/mL concentration of iodine-fulvic acid clathrate complex reduced the infectious dose of SARS-CoV-2 to 1% of its original value using Vero 76 cell culture [ 56 ].…”

“…The exact molecular mechanism of the antiviral effect of HSs is not yet clear. A recent study supposes that natural HSs samples as polyelectrolytes can block the interaction between coronaviral spike glycoproteins and cell membrane receptors [ 57 ]. In presenting indirect, host-related antiviral action, HSs can directly suppress oxidative stress, by recombination with intermediate free radicals.…”

“…A recent study shows that FA and iodine complex reduces significantly the virulence of SARS CoV-2 virus in a Vero 76 cell culture [ 56 ]. Natural HSs samples as polyelectrolytes containing numerous physiologically active elements (Fe, P, S, Si, K, Ca, Mn, Cu, Zn) as complexes, also significantly reduce viral infection of SARS CoV-2 in Vero E6 cell line [ 57 ]. HS could also be regarded as pre-biotics in the gut, playing a broad role in modulating the immune system.…”

Radiothermal Emission of Nanoparticles with a Complex Shape as a Tool for the Quality Control of Pharmaceuticals Containing Biologically Active Nanoparticles

“…The preparation of humic–fulvic acid was received from the Sistema Biotechnologii company as previously described [ 19 ].…”

Polyelectrolyte Chondroitin Sulfate Microgels as a Carrier Material for Rosmarinic Acid and Their Antioxidant Ability

“…Biological polyelectrolytes (PECs), also called biological polyelectrolyte complexes, generally comprise strong intermolecular interactions known as Coulomb’s interactions or electrostatic interactions between oppositely charged groups, e.g., cationic biopolymers such as chitosan [ 1 ], poly-l-lysine [ 2 ], poly-L-arginine [ 3 ], insulin [ 4 ], collagen [ 5 ], amino dextran, and 2-(diethylamino) ethyl dextran [ 6 ] with anionic biopolymers such as pectin [ 7 ], alginate [ 8 ], xanthan gum [ 1 ], dextran derivatives [ 6 ], hyaluronic acid [ 9 ], carrageenan [ 1 ], neem gum [ 10 ], heparin [ 11 ], chondroitin sulfate [ 12 ], carboxymethyl cellulose [ 13 ], humic substances [ 14 ], poly(γ-glutamic acid) [ 15 ], DNA [ 16 ], and siRNA [ 17 ]. Surfactant systems are generally used to prepare different polymeric systems, including spherically shaped polymeric particles at different sizes.…”