Development of an inhalable antiviral powder formulation against respiratory syncytial virus

Heida, Rick; Akkerman, Renate; Silva, Paulo H. Jacob; Lakerveld, Anke J.; Ortiz, Daniel; Bigogno, Chiara; Gasbarri, Matteo; Kasteren, Puck B. van; Stellacci, Francesco; Frijlink, Henderik W.; Huckriede, Anke; Hinrichs, Wouter L. J.

doi:10.1016/j.jconrel.2023.03.059

Cited by 3 publications

(4 citation statements)

References 41 publications

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“…Next, the filter was carefully removed from its holder ( Figure 2 b), and all the components (filter, filter holder and lid) were rinsed thoroughly with 5 mL of demineralized water to collect all the emitted powder. After sample collection, the emitted dose was analyzed by using the anthrone reaction, as previously described [ 23 ]. After the results showed that the small chamber volume, using 2 insert cylinders, yielded the highest emitted dose, the relationship between the flow rate and the emitted dose was determined for this condition using a fixed runtime of 3 min.…”

Section: Methodsmentioning

confidence: 99%

Performance Testing of a Homemade Aerosol Generator for Pulmonary Administration of Dry Powder Formulations to Mice

Heida,

Hagedoorn,

van Meel

et al. 2023

Pharmaceutics

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A challenge in the development of dry powder formulations for inhalation is the poor reproducibility of their administration to small laboratory animals. The currently used devices for the pulmonary administration of dry powder formulations to small rodents often function sub-optimally as they use the same puff of air for both powder dispersion and aerosol delivery. As a result, either the air volume and flow rate are too low for complete powder deagglomeration or they are too high for effective aerosol delivery to the lungs of the animal. Therefore, novel and better devices are desired. We here present an aerosol generator designed to administer a pre-generated aerosol to the lungs of mice. By mapping the complex relationship between the airflow rate, delivery time and emitted dose, we were able to control the amount of powder being delivered from the aerosol generator. The emitted aerosol had a size range favorable for lung deposition and could be measured reproducibly. Nevertheless, in vivo fluorescent imaging still revealed considerable differences between the mice in terms of the dose deposited and the distribution of powder over the lungs, suggesting that a certain biological variation in lung deposition is inevitable.

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Section: Methodsmentioning

confidence: 99%

Performance Testing of a Homemade Aerosol Generator for Pulmonary Administration of Dry Powder Formulations to Mice

Heida,

Hagedoorn,

van Meel

et al. 2023

Pharmaceutics

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“…19 Current authoritative research strongly supports the notion that inhibiting RSV infection by targeting HSPGs holds promise as an effective approach for reducing viral infections. 18,19,25 Noteworthy studies have explored various strategies for this purpose. Francesco Stellacci, for instance, has introduced the concept of employing nanoparticle formulated mimics of HSPGs, which has demonstrated effectiveness in inhibiting RSV infection both in vivo and in vitro.…”

Section: Food and Function Papermentioning

confidence: 99%

“…18,38 Another study has presented a broadspectrum entry inhibitor capable of neutralizing RSV, a virus that relies on HSPGs for host cell entry. 25 In addition to HSPG analogs, direct binding to HSPG has also proven effective in inhibiting RSV infection. Some researchers have designed peptides with the ability to bind to HSPGs, thereby blocking RSV attachment and infectivity.…”

Section: Food and Function Papermentioning

confidence: 99%

“…Numerous HSPG-mimicking materials, including heparin, sulfated polysaccharides, as well as sulfonic-acid-decorated polymers, dendrimers, and nanoparticles, have been tested and demonstrated robust anti-RSV effects in in vitro and in vivo studies. 18,[25][26][27] Additionally, some researchers have designed molecules that bind to HSPGs, thereby blocking the virus from attaching to HSPGs and preventing further RSV infection. 21,28 Given the broad-spectrum antiviral properties of resveratrol and the significance of HSPGs in this context, it is hypothesized that resveratrol may inhibit RSV infection by modulating HSPGs.…”

Section: Introductionmentioning

confidence: 99%

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Resveratrol inhibits respiratory syncytial virus replication by targeting heparan sulfate proteoglycans

Xiong,

Tao,

et al. 2024

Food Funct.

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Synthetic heparan sulfate mimics based on chitosan derivatives show broad-spectrum antiviral activity

Geller,

Revuelta,

Rusu

et al. 2024

Preprint

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Enveloped viruses enter cells by binding to receptors present on host cell membranes, which trigger internalization and membrane fusion. For many viruses, this either directly or indirectly involves interaction with membrane-anchored carbohydrates, such as heparan sulfate, providing a potential target for a broad-spectrum antiviral approach. Based on this hypothesis, we screened a library of functionalized chitosan sulfates that mimic heparan sulfate in cellular membranes for inhibition of SARS-CoV-2 and respiratory syncytial virus (RSV) entry. An array of compounds blocking SARS-CoV-2 and RSV were identified, with the lead compound displaying broad-spectrum activity against multiple viral strains and clinical isolates. Mechanism of action studies showed the drug to block viral entry irreversibly, likely via a virucidal mechanism. Importantly, the drug was non-toxic in vivo and showed potent post-exposure therapeutic activity against both SARS-CoV-2 and RSV. Together, these results highlight the potential of functionalized carbohydrates as broad-spectrum antivirals targeting respiratory viruses.

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Development of an inhalable antiviral powder formulation against respiratory syncytial virus

Cited by 3 publications

References 41 publications

Performance Testing of a Homemade Aerosol Generator for Pulmonary Administration of Dry Powder Formulations to Mice

Performance Testing of a Homemade Aerosol Generator for Pulmonary Administration of Dry Powder Formulations to Mice

Resveratrol inhibits respiratory syncytial virus replication by targeting heparan sulfate proteoglycans

Synthetic heparan sulfate mimics based on chitosan derivatives show broad-spectrum antiviral activity

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