Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Evaluation of Novel Nasal Mucoadhesive Nanoformulations Containing Lipid-Soluble EGCG for Long COVID Treatment

Version 1 : Received: 29 April 2024 / Approved: 30 April 2024 / Online: 30 April 2024 (11:45:40 CEST)

How to cite: Frank, N.; Dickinson, D.; Lovett, G.; Liu, Y.; Yu, H.; Cai, J.; Yao, B.; Jiang, X.; Hsu, S. Evaluation of Novel Nasal Mucoadhesive Nanoformulations Containing Lipid-Soluble EGCG for Long COVID Treatment. Preprints 2024, 2024041974. https://doi.org/10.20944/preprints202404.1974.v1 Frank, N.; Dickinson, D.; Lovett, G.; Liu, Y.; Yu, H.; Cai, J.; Yao, B.; Jiang, X.; Hsu, S. Evaluation of Novel Nasal Mucoadhesive Nanoformulations Containing Lipid-Soluble EGCG for Long COVID Treatment. Preprints 2024, 2024041974. https://doi.org/10.20944/preprints202404.1974.v1

Abstract

Neurologic symptoms associated with Long COVID result from the persistent infection of SARS-CoV-2 in the nasal neuroepithelial cells, leading to inflammation in the central nervous sys-tem (CNS). As of today, there is no evidence that vaccines or medications can clear the persistent viral infection in the olfactory mucosa. Recently published clinical data demonstrate that only 5% of Long COVID anosmia patients have fully recovered during the past 2 years and 10.4% of COVID patients are still symptomatic 18 months post infection. Our group demonstrated that ep-igallocatechin-3-gallate-monopalmitate (EC16m) nanoformulations possess strong antiviral activ-ity against human coronavirus, suggesting this green tea-derived compound in nanoparticle for-mulations could be developed as an intranasally delivered new drug targeting the persistent SARS-CoV-2 infection, as well as inflammation and oxidative stress in the CNS, leading to resto-ration of neurologic functions. The objective of the current study is to evaluate the mucociliary safety of the EC16m nasal nanoformulations and the efficacy against human coronavirus. Meth-ods: nanoparticle size and Zeta potential were measured using the ZetaView Nanoparticle Tracking Analysis system; mucociliary safety was determined using MucilAir Human Nasal Epi-thelium Model; contact antiviral activity and post-infection inhibition against OC43 viral strain were assessed by TCID50 assay for cytopathic effect on MRC-5 cells. Results: the saline-based EC16 mucoadhesive nanoformulations containing 0.005 to 0.02% w/v EC16m have no significant difference in comparison to saline (0.9% NaCl) on tissue integrity, cytotoxicity, and cilia beat fre-quency. A 5-minute contact inactivated 99.9% of the β-coronavirus OC43. OC43 viral replication was inhibited by >99% after infected MAR-5 cells were treated with one of the formulations. Con-clusion: the saline-based novel EC16m mucoadhesive nasal nanoformulations rapidly inactivated human coronavirus with mucociliary safety measurements comparable to saline, a solution widely used for nasal applications.

Keywords

Respiratory virus; Long COVID; Nasal drug; EGCG-palmitate; Nanoformulations

Subject

Medicine and Pharmacology, Other

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