Nanoformulation Composed of Ellagic Acid and Functionalized Zinc Oxide Nanoparticles Inactivates DNA and RNA Viruses

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2021 Dec 28

PMID 34959455

Citations 12

Authors

Khaled AbouAitah

Abdou K Allayh

Jacek Wojnarowicz

Yasser M Shaker

Anna Swiderska-Sroda

Witold Lojkowski

Affiliations

Soon will be listed here.

Abstract

The COVID-19 pandemic has strongly impacted daily life across the globe and caused millions of infections and deaths. No drug therapy has yet been approved for the clinic. In the current study, we provide a novel nanoformulation against DNA and RNA viruses that also has a potential for implementation against COVID-19. The inorganic-organic hybrid nanoformulation is composed of zinc oxide nanoparticles (ZnO NPs) functionalized with triptycene organic molecules (TRP) via EDC/NHS coupling chemistry and impregnated with a natural agent, ellagic acid (ELG), via non-covalent interactions. The physicochemical properties of prepared materials were identified with several techniques. The hybrid nanoformulation contained 9.5 wt.% TRP and was loaded with up to 33.3 wt.% ELG. ELG alone exhibited higher cytotoxicity than both the ZnO NPs and nanoformulation against host cells. The nanoformulation efficiently inhibited viruses, compared to ZnO NPs or ELG alone. For H1N1 and HCoV-229E (RNA viruses), the nanoformulation had a therapeutic index of 77.3 and 75.7, respectively. For HSV-2 and Ad-7 (DNA viruses), the nanoformulation had a therapeutic index of 57.5 and 51.7, respectively. In addition, the nanoformulation showed direct inactivation of HCoV-229E via a virucidal mechanism. The inhibition by this mechanism was > 60%. Thus, the nanoformulation is a potentially safe and low-cost hybrid agent that can be explored as a new alternative therapeutic strategy for COVID-19.

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References

Yang K, Lin J, Tsai H, Hsu C, Shih V, Hu C . Nanotechnology advances in pathogen- and host-targeted antiviral delivery: multipronged therapeutic intervention for pandemic control. Drug Deliv Transl Res. 2021; 11(4):1420-1437. PMC: 7982277. DOI: 10.1007/s13346-021-00965-y. View

Innocenzi P, Stagi L . Carbon-based antiviral nanomaterials: graphene, C-dots, and fullerenes. A perspective. Chem Sci. 2020; 11(26):6606-6622. PMC: 7499860. DOI: 10.1039/d0sc02658a. View

Hakeem A, Duan R, Zahid F, Dong C, Wang B, Hong F . Dual stimuli-responsive nano-vehicles for controlled drug delivery: mesoporous silica nanoparticles end-capped with natural chitosan. Chem Commun (Camb). 2014; 50(87):13268-71. DOI: 10.1039/c4cc04383a. View

Mei M, Tan X . Current Strategies of Antiviral Drug Discovery for COVID-19. Front Mol Biosci. 2021; 8:671263. PMC: 8155633. DOI: 10.3389/fmolb.2021.671263. View

Pavlova E, Zografov N, Simeonova L . Comparative study on the antioxidant capacities of synthetic influenza inhibitors and ellagic acid in model systems. Biomed Pharmacother. 2016; 83:755-762. DOI: 10.1016/j.biopha.2016.07.046. View

Chong J, Ardakani S, Smith K, MacLachlan M . Triptycene-based metal salphens--exploiting intrinsic molecular porosity for gas storage. Chemistry. 2009; 15(44):11824-8. DOI: 10.1002/chem.200902188. View

Ghaffari H, Tavakoli A, Moradi A, Tabarraei A, Bokharaei-Salim F, Zahmatkeshan M . Inhibition of H1N1 influenza virus infection by zinc oxide nanoparticles: another emerging application of nanomedicine. J Biomed Sci. 2019; 26(1):70. PMC: 6734352. DOI: 10.1186/s12929-019-0563-4. View

Tharayil A, Rajakumari R, Kumar A, Choudhary M, Palit P, Thomas S . New insights into application of nanoparticles in the diagnosis and screening of novel coronavirus (SARS-CoV-2). Emergent Mater. 2021; 4(1):101-117. PMC: 8010296. DOI: 10.1007/s42247-021-00182-w. View

AbouAitah K, Piotrowska U, Wojnarowicz J, Swiderska-Sroda A, El-Desoky A, Lojkowski W . Enhanced Activity and Sustained Release of Protocatechuic Acid, a Natural Antibacterial Agent, from Hybrid Nanoformulations with Zinc Oxide Nanoparticles. Int J Mol Sci. 2021; 22(10). PMC: 8156785. DOI: 10.3390/ijms22105287. View

10.

Sadique M, Yadav S, Ranjan P, Verma S, Salammal S, Khan M . High-performance antiviral nano-systems as a shield to inhibit viral infections: SARS-CoV-2 as a model case study. J Mater Chem B. 2021; 9(23):4620-4642. DOI: 10.1039/d1tb00472g. View

11.

Sundararajan A, Ganapathy R, Huan L, Dunlap J, Webby R, Kotwal G . Influenza virus variation in susceptibility to inactivation by pomegranate polyphenols is determined by envelope glycoproteins. Antiviral Res. 2010; 88(1):1-9. PMC: 7114265. DOI: 10.1016/j.antiviral.2010.06.014. View

12.

Shah S, Chougule M, Kotha A, Kashikar R, Godugu C, Raghuvanshi R . Nanomedicine based approaches for combating viral infections. J Control Release. 2021; 338:80-104. PMC: 8526416. DOI: 10.1016/j.jconrel.2021.08.011. View

13.

Feifel S, Lisdat F . Silica nanoparticles for the layer-by-layer assembly of fully electro-active cytochrome c multilayers. J Nanobiotechnology. 2012; 9:59. PMC: 3278367. DOI: 10.1186/1477-3155-9-59. View

14.

Hao L, Hu Y, Zhang Y, Wei W, Hou X, Guo Y . Enhancing the mechanical performance of poly(ether ether ketone)/zinc oxide nanocomposites to provide promising biomaterials for trauma and orthopedic implants. RSC Adv. 2022; 8(48):27304-27317. PMC: 9083298. DOI: 10.1039/c8ra01736k. View

15.

Karimi A, Moradi M, Rabiei M, Alidadi S . In vitro anti-adenoviral activities of ethanol extract, fractions, and main phenolic compounds of pomegranate ( L.) peel. Antivir Chem Chemother. 2020; 28:2040206620916571. PMC: 7169357. DOI: 10.1177/2040206620916571. View

16.

Acquadro S, Civra A, Cagliero C, Marengo A, Ritta M, Francese R . Punica granatum Leaf Ethanolic Extract and Ellagic Acid as Inhibitors of Zika Virus Infection. Planta Med. 2020; 86(18):1363-1374. DOI: 10.1055/a-1232-5705. View

17.

Galdiero S, Falanga A, Vitiello M, Cantisani M, Marra V, Galdiero M . Silver nanoparticles as potential antiviral agents. Molecules. 2011; 16(10):8894-918. PMC: 6264685. DOI: 10.3390/molecules16108894. View

18.

Wojnarowicz J, Chudoba T, Gierlotka S, Lojkowski W . Effect of Microwave Radiation Power on the Size of Aggregates of ZnO NPs Prepared Using Microwave Solvothermal Synthesis. Nanomaterials (Basel). 2018; 8(5). PMC: 5977357. DOI: 10.3390/nano8050343. View

19.

Luo M, Shen C, Feltis B, Martin L, Hughes A, Wright P . Reducing ZnO nanoparticle cytotoxicity by surface modification. Nanoscale. 2014; 6(11):5791-8. DOI: 10.1039/c4nr00458b. View

20.

Kang E, Kown T, Oh G, Park W, Park S, Park S . The flavonoid ellagic acid from a medicinal herb inhibits host immune tolerance induced by the hepatitis B virus-e antigen. Antiviral Res. 2006; 72(2):100-6. DOI: 10.1016/j.antiviral.2006.04.006. View