Nanoformulated Remdesivir with Extremely Low Content of Poly(2-oxazoline)-Based Stabilizer for Aerosol Treatment of COVID-19.

Autor: Ramsey JD; Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Stewart IE; Technology Advancement and Commercialization, RTI International, Research Triangle, NC, 27709, USA., Madden EA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Lim C; Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Hwang D; Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Heise MT; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA., Hickey AJ; Technology Advancement and Commercialization, RTI International, Research Triangle, NC, 27709, USA., Kabanov AV; Center for Nanotechnology in Drug Delivery and Division of Pharmacoengineering and Molecular Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.; Laboratory of Chemical Design of Bionanomaterials, Faculty of Chemistry, M.V. Lomonosov Moscow State University, Moscow, 119992, Russia.
Jazyk: angličtina
Zdroj: Macromolecular bioscience [Macromol Biosci] 2022 Aug; Vol. 22 (8), pp. e2200056. Date of Electronic Publication: 2022 May 26.
DOI: 10.1002/mabi.202200056
Abstrakt: The rise of the novel virus SARS-CoV2 which causes the disease known as COVID-19 has led to a global pandemic claiming millions of lives. With no clinically approved treatment for COVID-19, physicians initially struggled to treat the disease, and a need remains for improved antiviral therapies in this area. It is conceived early in the pandemic that an inhalable formulation of the drug remdesivir which directly targets the virus at the site of infection could improve therapeutic outcomes in COVID-19. A set of requirements are developed that would be conducive to rapid drug approval: 1) try to use GRAS reagents 2) minimize excipient concentration and 3) achieve a working concentration of 5 mg/mL remdesivir to obtain a deliverable dose which is 5-10% of the IV dose. In this work, it is discovered that Poly(2-oxazoline) block copolymers can stabilize drug nanocrystal suspensions and provide suitable formulation characteristics for aerosol delivery while maintaining antiviral efficacy. The authors believe POx block copolymers can be used as a semi-ubiquitous stabilizer for the rapid development of nanocrystal formulations for new and existing diseases.
(© 2022 Wiley-VCH GmbH.)
Databáze: MEDLINE
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