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Inhaled therapy for COVID-19: Considerations of drugs, formulations and devices
Tushar Saha1, Miguel E Quiñones-Mateu2, Shyamal C Das1
1School of Pharmacy, University of Otago, Dunedin, New Zealand.
Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent responsible for the COVID-19 pandemic, has outspread at full tilt across the world. Although several effective vaccines continue to be deployed, reliable antiviral treatments have yet to be developed against this disease. Currently, available therapeutics for COVID-19 include repurposed, and a few novel drugs. Many drugs have been promising in preclinical studies, but a majority of these drugs have shown little or no efficacy in clinical studies. One of the major reasons is the insufficient drug concentration in the lung, the primary target site of infection for SARS-CoV-2, from the administration of drugs through oral or intravenous routes. Higher effective doses administered through these routes could also lead to adverse side effects. For this reason, inhaled treatments are being tested as an efficient approach for COVID-19, allowing lower doses of drugs ensuring higher concentrations of the drug(s) in the lung. The inhaled treatment combining two or more antiviral drugs will increase potency and reduce the possibility of selecting for SARS-CoV-2 variants with reduced drug susceptibility. Finally, the appropriate drug combination needs to be delivered using a suitable system. Here, we review the current treatment for COVID-19 and their limitations, discussing the advantages of mono and combinational inhaled therapy with a brief outline of the recently reformulated anti-SARS-CoV-2 agents as inhaled formulations. The selection of appropriate delivery devices for inhalation and associated key considerations including the formulation challenges are also discussed.
Insights
Inhaled antiviral therapies offer a promising approach to treating COVID-19 by delivering drugs directly to the lungs. Combining multiple drugs via inhalation may enhance efficacy and combat SARS-CoV-2 variants.
Area of Science:
- Pulmonary Medicine
- Infectious Diseases
- Drug Delivery Systems
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the COVID-19 pandemic, with limited effective antiviral treatments available.
- Current treatments, including repurposed and novel drugs, often show insufficient efficacy due to poor lung drug concentrations and potential side effects from oral or intravenous administration.
- Developing effective antiviral strategies remains critical despite widespread vaccination efforts.
Purpose of the Study:
- To review current COVID-19 treatments and their limitations.
- To discuss the advantages of inhaled monotherapy and combination therapy against SARS-CoV-2.
- To explore reformulated anti-SARS-CoV-2 agents as inhaled formulations and suitable delivery systems.
Main Methods:
- Literature review of existing COVID-19 therapeutics.
- Analysis of preclinical and clinical study data on drug efficacy and delivery routes.
- Discussion of formulation challenges and delivery device considerations for inhaled therapies.
Main Results:
- Oral and intravenous drug administration routes result in suboptimal lung concentrations for treating SARS-CoV-2.
- Inhaled therapies allow for lower drug doses with higher lung concentrations, potentially reducing systemic side effects.
- Combinational inhaled therapy can increase potency and mitigate the emergence of drug-resistant SARS-CoV-2 variants.
Conclusions:
- Inhaled antiviral treatments represent an efficient strategy for managing COVID-19 by targeting the primary infection site.
- Combination inhaled therapy holds significant potential for improved efficacy and overcoming drug resistance.
- Further research into appropriate formulations and delivery devices is crucial for optimizing inhaled anti-SARS-CoV-2 treatments.
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