Intranasal Antiviral Drug Delivery and Coronavirus Disease 2019 (COVID‐19): A State of the Art Review

Higgins, Thomas S.; Wu, Arthur W.; Illing, Elisa A.; Sokoloski, Kevin J.; Weaver, Bree; Anthony, Benjamin P.; Hughes, Nathan; Ting, Jonathan Y.

doi:10.1177/0194599820933170

Cited by 45 publications

(40 citation statements)

References 86 publications

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“…5). SARS-CoV-2 is mainly present in the nasopharynx and lungs 31,32 . Differing from many previously reported systemic delivery route, Nb 15 -Nb H -Nb 15 was delivered to the site of infection.…”

Section: Discussionmentioning

confidence: 99%

“…Differing from many previously reported systemic delivery route, Nb 15 -Nb H -Nb 15 was delivered to the site of infection. Direct administration to the airways is likely to provide faster and more robust antiviral activity in the respiratory tract, where the virus gains entry and replicate 16,32 , as intranasal delivery has been shown to result in fast and efficient drug delivery to the main site of SARS-CoV-2 infection, i.e., the upper and lower respiratory tract 32 . Indeed, the therapeutic effect of topical administration of ALX-0171 displayed promising results in reducing the RSV viral load 14,16 .…”

Section: Discussionmentioning

confidence: 99%

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A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration

Cheng

et al. 2021

Preprint

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The dramatically expanding COVID-19 needs multiple effective countermeasures. Neutralizing antibodies are a potential therapeutic strategy for treating COVID-19. A number of neutralizing nanobodies (Nbs) were reported for their in vitro activities. However, in vivo protection of these nanobodies was not reported in animal models. In the current report, we characterized several RBD-specific Nbs isolated from a screen of an Nb library derived from an alpaca immunized with SARS-CoV-2 spike glycoprotein (S); among them, three Nbs exhibited picomolar potency against SARS-CoV-2 live virus, pseudotyped viruses, and 15 circulating SARS-CoV-2 variants. To improve the efficacy, various configurations of Nbs were engineered. Nb15-NbH-Nb15, a novel trimer constituted of three Nbs, was constructed to be bispecific for human serum albumin (HSA) and RBD of SARS-CoV-2. Nb15-NbH-Nb15 exhibited sub-ng/ml neutralization potency against the wild-type and currently circulating variants of SARS-CoV-2 with a long half-life in vivo. In addition, we showed that intranasal administration of Nb15-NbH-Nb15 provided 100% protection for both prophylactic and therapeutic purposes against SARS-CoV-2 infection in transgenic hACE2 mice. Nb15-NbH-Nb15 is a potential candidate for both prevention and treatment of SARS-CoV-2 through respiratory administration.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration

Cheng

et al. 2021

Preprint

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“…This strategy can lead to a more efficient treatment and clinical prognosis. Also, computational fluid dynamics could be utilized to determine appropriate particle size, location of magnet, spray velocity, and dosing, for effective therapies for pulmonary viral infectious diseases like COVID-19 [ 241 ].…”

Section: Discussionmentioning

confidence: 99%

Magnetic particle targeting for diagnosis and therapy of lung cancers

Saadat

Manshadi

Mohammadi

et al. 2020

Journal of Controlled Release

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Over the past decade, the growing interest in targeted lung cancer therapy has guided researchers toward the cutting edge of controlled drug delivery, particularly magnetic particle targeting. Targeting of tissues by magnetic particles has tackled several limitations of traditional drug delivery methods for both cancer detection (e.g., using magnetic resonance imaging) and therapy. Delivery of magnetic particles offers the key advantage of high efficiency in the local deposition of drugs in the target tissue with the least harmful effect on other healthy tissues. This review first overviews clinical aspects of lung morphology and pathogenesis as well as clinical features of lung cancer. It is followed by reviewing the advances in using magnetic particles for diagnosis and therapy of lung cancers: (i) a combination of magnetic particle targeting with MRI imaging for diagnosis and screening of lung cancers, (ii) magnetic drug targeting (MDT) through either intravenous injection and pulmonary delivery for lung cancer therapy, and (iii) computational simulations that models new and effective approaches for magnetic particle drug delivery to the lung, all supporting improved lung cancer treatment. The review further discusses future opportunities to improve the clinical performance of MDT for diagnosis and treatment of lung cancer and highlights clinical therapy application of the MDT as a new horizon to cure with minimal side effects a wide variety of lung diseases and possibly other acute respiratory syndromes (COVID-19, MERS, and SARS).

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“…Drug combination might help to reduce the dose or the time of application of this mixed therapy. Nasal administration is also a promising alternative that might overcome both toxicity effects and effective concentration challenges [63].…”

Section: Discussionmentioning

confidence: 99%

Understanding Severe Acute Respiratory Syndrome Coronavirus 2 Replication to Design Efficient Drug Combination Therapies

et al. 2020

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Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its disease COVID-19 has strongly encouraged the search for antiviral compounds. Most of the evaluated drugs against SARS-CoV-2 derive from drug repurposing of Food and Drug Administration-approved molecules. These drugs have as target three major processes: (1) early stages of virus-cell interaction, (2) viral proteases, and (3) the viral RNA-dependent RNA polymerase. Summary: This review focused on the basic principles of virology and pharmacology to understand the importance of early stages of virus-cell interaction as therapeutic targets and other main processes vital for SARS-CoV-2 replication. Furthermore, we focused on describing the main targets associated with SARS-CoV-2 antiviral therapy and the rationale of drug combinations for efficiently suppressing viral replication. Key Messages: We hypothesized that blocking of both entry mechanisms could allow a more effective antiviral effect compared to the partial results obtained with chloroquine or its derivatives alone. This approach, already used to achieve an antiviral effect higher than that offered by every single drug administered separately, has been successfully applied in several viral infections such as HIV and HCV. This review will contribute to expanding the perception of the possible therapeutic targets in SARS-CoV-2 infection and highlight the benefits of using combination therapies.

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Intranasal Antiviral Drug Delivery and Coronavirus Disease 2019 (COVID‐19): A State of the Art Review

Cited by 45 publications

References 86 publications

A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration

A potent bispecific nanobody protects hACE2 mice against SARS-CoV-2 infection via intranasal administration

Magnetic particle targeting for diagnosis and therapy of lung cancers

Understanding Severe Acute Respiratory Syndrome Coronavirus 2 Replication to Design Efficient Drug Combination Therapies

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