Nanobubble Ozone Stored in Hyaluronic Acid Decorated Liposomes: Antibacterial, Anti-SARS-CoV-2 Effect and Biocompatibility Tests

• Published in: International journal of nanomedicine Vol. 17; pp. 351 - 379
• Main Authors: Sabancı, Ahmet Umit, Erkan Alkan, Perihan, Mujde, Cem, Polat, Hivda Ulbeği, Ornek Erguzeloglu, Cemre, Bisgin, Atil, Ozakin, Cuneyt, Temel, Sehime G
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2022; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: Air pollution; Amino acids; Analysis; Animals; Anti-Bacterial Agents - pharmacology; anti-microbial; anti-viral; Antibacterial agents; Antiviral agents; Biocompatibility; Chlorocebus aethiops; Coronaviruses; COVID-19; Cricetinae; Cytomegalovirus; Disease transmission; E coli; Escherichia coli; Female; Health aspects; Humans; Hyaluronic Acid; Laboratories; liposome; Liposomes; Male; Mice; nanobubble; Original Research; Ozone; Prevention; Rabbits; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Streptococcus infections; Vero Cells; Viral infections; Viruses; anti-viral; nanobubble; anti-microbial; liposome; ozone; hyaluronic acid
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S328090

SARS-CoV-2-infected individuals may be asymptomatic, and therefore, the virus is highly contagious. We aimed to develop an agent to control viral replication in the upper respiratory tract and to prevent progression of the disease into the lower airways as well as inter-individual transmission. For this purpose, we investigated the antibacterial and antiviral activities of our novel nanobubble ozonated hyaluronic acid-decorated liposomal (NOHAL) solution, developed by using nanotechnology. The MIC levels of NOHAL solution were determined on blood agar cultures of (ATCC 6538), (ATCC 49619) and (ATCC 25922). The in vitro anti-viral activity of NOHAL solution was studied using recombinant SARS-CoV-2 copies of the original virus, grown in Vero cells generated by reverse genetic technology. Human primary lung epithelial cells obtained by bronchoscopy or lung resection were used for cell viability tests using flow cytometry analysis. The cytotoxicity testing was performed using the BALB/c 3T3 (CCL-163) cell line. Skin, oral, nasal and ocular irritation tests were performed using New Zealand albino rabbits, Syrian hamsters, BALB c mice and New Zealand albino rabbits of both sexes. Bacterial growth was prevented by NOHAL solution in a time-/dose-dependent manner. In vivo or in vitro experiments did not show any toxicity of NOHAL solution. No cytotoxicity was recorded on cell viability. No skin, oral, nasal or ocular toxicities were recorded. In addition, in a SARS-CoV-2 mouse infection model, NOHAL solution diminished the viral RNA levels effectively in nasopharyngeal and lung samples after its prophylactic intranasal application. NOHAL solution has the potential to reduce or prevent the spread of SARS-CoV-2 through the nose and/or oral cavity. The clinical efficacy of this solution needs to be tested in order to determine its efficacy in the early phase of COVID-19.