Objectives: We present explicit candidate formulations and realistic delivery dosages for a broad-range antimicrobial combination treatment – effective for suppression of both viral and bacterial respiratory infections – based on inhalation delivery of nanoparticle colloids (NpC) such as silver nanoparticles. Special evaluation is given to Corona viruses. We are not aware of any published prior theoretical or clinical research on medicinal inhalation of silver particles. Here we lay the grounds for such clinical evaluations to be done, from formulations composition to dosage calculation, delivery method, mechanism of action, and clinical safety analysis. Regarding the mechanism of action. Our core calculations are phenomenological and are not dependent on mechanisms. Yet, the understanding of mechanisms may guide future optimization and alternatives. Unlike bacteria, we contend that the broad rage anti-viral effectiveness of NpC is a consequence of the purely electrostatic nature of the interaction. The spike proteins of many viruses are positively charged (including Influenza and Corona viruses), promoting binding to the predominantly negative surface charge of the host cell receptors (such as ACE2) [42]. Correspondingly, the high negative surface Zeta-potential of the nanoparticles is leading to selective binding of the nanoparticles specifically to the spike proteins of viruses and thereby neutralizing their receptor binding affinity. Hence, nanoparticles with high Zeta potential are preferred. This also explains why the positively charged silver ions (Ag+) play a completely different role, if any. The silver by itself is unimportant, other than as a manufacturing method for generating a stable charged composite nanoparticles colloid. Altogether, any colloid of some nanoparticles of size primarily between 2-10nm and a high negative Zeta-potential of more than -20 mV would work just as effectively as silver NpC. Correspondingly, we conjecture that viruses whose spike proteins binding sites are negatively charged will not be affected by the standard silver NpC, and thus would require a neutralization by some other colloid with positive Zeta-potential nanoparticles. Clinically, the treatment formulations may be most effectively applied as a first-line intervention at an early stage of respiratory infections, i.e., when mostly affecting the upper respiratory system and bronchial tree. For example, the formulations could be used to control local outbreaks of COVID-19 via early stage home treatment. We note that similar NpC dosages also provide anti-bacterial effectiveness. Thus, we propose that for hospital ventilator associated pneumonia (VAP), inhalation delivery of NpC can be implemented prophylactically to lower VAP risk. The non-development of silver NpC anti-viral drug treatments until now is a market failure, likely due to unclear patents environment, making such developments unattractive for big pharma companies. Unfortunately, the gap between promising academic research and market regulatory approved products has been left to be filled by “alternative medicine” charlatans – giving bad publicity to the whole field. To overcome this market failure situation, this article also serves as a proclamation and blueprint for an open-source drug development program to realize it. Potential development parties – academic, clinical, manufacturing, and commercial – are invited to join via the dedicated website noted in our address. Method: We analyse: (a) nanoparticle size and material composition options, with special attention to the stabilization (capping) choice of materials, (b) the required effective inhibitory concentration (IC) in target respiratory system tissue, (c) the delivery method and associated treatment dosages. Building towards potential clinical evaluation, we discuss the evidence for safety of the proposed treatment based on published tests and guidelines in the EU and USA for inhalation of silver nanoparticles.
Nanomedicine Formulations for Respiratory Infections by Inhalation Delivery: Covid-19 and Beyond
