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    Review of 'Formulations for COVID-19 Early Stage Treatment via Silver Nanoparticles Inhalation Delivery at Home and Hospital'

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    Formulations for COVID-19 Early Stage Treatment via Silver Nanoparticles Inhalation Delivery at Home and HospitalCrossref
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    Formulations for COVID-19 Early Stage Treatment via Silver Nanoparticles Inhalation Delivery at Home and Hospital

     Oron Zachar (corresponding) (2020)
    Objectives : For suppressing both viral and bacterial respiratory infections, we investigate the possibility of obtaining real effective minimal inhibitory concentration (MIC) of silver nanoparticles in various respiratory system target locations. Applications include (i) control local outbreaks of COVID-19 via early stage home treatment, and (ii) lower the risk of ventilator associated pneumonia (VAP) in hospital ICU. Our prime objective is to propose a first line intervention measure with the potential to suppress proliferation of the viral infection across the respiratory system, thereby giving more time for proper immune system response and lowering the risk for aggravation and spread of the infection. We further discuss the available credible evidence for human safety consideration, by inhalation delivery, for facilitating immediate clinical trials. In addition, we discuss possible manufacturing and commercial availability of the method elements for near term wide public usage. Method : Based on previously published experimental data, on the antiviral effectiveness of colloidal silver, we propose a model method and computation for achieving antiviral MIC of silver particles in various respiratory system locations, by: (a) analysing the nanoparticle size dependent required concentration. (b) computing the required aerosol delivery characteristics. In order to compute the require delivery dosage, we take into account deposition fraction losses and also inhalation time fraction of the normal breathing cycle. We evaluate independent targeting of: (i) the trachea-bronchial tree (mucus volume of about 1cc), and (ii) the alveoli (total mucus volume of about 10cc). Results : The dosage is highly sensitive to the silver nanoparticle size, with 3nm - 7nm being the optimal size. Effective antibacterial MIC 10 μg/ml is estimated, but for more certainty 25 μg/ml is a reasonable target concentration to achieve in the mucus fluid of the respiratory system. In particular, using colloidal silver of 5nm particles, delivering inhalation of standard 5μ diameter droplets aerosol (e.g., using off-the-shelf ultrasonic mesh nebulizers), we assert that sufficient MIC can be achieved with: (i) depositing a total of just 0.25cc of a 100ppm (μg/ml) source concentration in the bronchial tree, and (ii) depositing a total of 1cc of a 250ppm (μg/ml) source concentration in the lungs alveoli. Yet, after accounting for deposition losses and due to the fact that active inhalation time is just about 1/3 of the breathing cycle, we find that that practical effective MIC can be achieved by these aerosolising dosages: (a) for the upper airways and bronchial tree use 2cc of a 100 μg/ml colloidal silver source, while (b) for lungs alveoli delivery use 6cc of a 200 μg/ml colloidal silver source. This would be reduced by a factor 3 if a breath actuated ultrasonic nebulizer is used. Conclusions : We conclude that effective MIC is achievable, both in the bronchial tree and in the alveoli (though the specific aerosol prescription may differ). Since respiratory infections start most commonly in the upper airways, it would be best to use the presented method early on as a first line treatment to suppress the progression of the infection. The required formulations are presently not available on the market but are easy to mass produce OTC in principle. Using off-the-shelf ultrasonic nebulizers and providable OTC colloidal silver formulations, we posit that our suggested method can be used precautionarily at home by anyone feeling the early signs of a potential infection. In addition, due to the anti-bacterial properties of colloidal silver, our method can serve in hospital intensive care units (ICU) as a new standard of care prophylactic treatment for ventilator acquired pneumonia (VAP).
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      Review information

      10.14293/S2199-1006.1.SOR-MED.APHBJEO.v1.RLNMLD

      This work has been published open access under Creative Commons Attribution License CC BY 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com.

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      Review text

      A peer review should focus on the content but here it is necessary to comment on the single author of this preprint. This is his first article or preprint that has anything to do with biology or chemistry. The last article he published dates from more than 15 years ago and deals with theoretical physics. He has no academic affiliation but he is CEO of two companies. The one he uses to sign the article does not seem to have any existence beyond his profile (according to a Google search). The other one, Biovo technologies, develops/sells “groundbreaking medical devices […]” and its “premier product line – Airway Medix – presents a line of disposable respiratory devices used for mechanically ventilated patients.” In spite of this, there is no conflict of interest declaration in the preprint.

      The article itself makes the case for starting clinical trials consisting in injecting large amounts of silver nanoparticles by inhalation in Covid-19 patients. There is no preclinical work to support this. The in vitro work, from the literature, is on other viruses, and is of poor quality, often in completely artificial and unrealistic models. There is simply no reliable evidence or efficacy model to support exploring this route. The model – if I can use this word - shown in figure 5 is completely naïve.

      In general, and particularly in a time of pandemic, sharing articles that make unsupported recommendations for therapeutic interventions is highly problematic. Whilst preprint servers have a role to play in accelerating the circulation of information, there is also a risk that they contribute to amplify bad science noise (at best) or even cause harm (at worst).

       

       

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