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Remdesivir-loaded bis-MPA hyperbranched dendritic nanocarriers for pulmonary delivery

Remdesivir is the only clinically available antiviral drug for the treatment of COVID-19. However, its very limited aqueous solubility confines its therapeutic activity and the development of novel inhaled nano-based drug delivery systems of remdesivir for enhanced lung tissue targeting and efficacy...

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Autores principales: Halevas, Eleftherios, Mavroidi, Barbara, Kokotidou, Chrysoula, Moschona, Alexandra, Sagnou, Marina, Mitraki, Anna, Litsardakis, George, Pelecanou, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364662/
https://www.ncbi.nlm.nih.gov/pubmed/35966803
http://dx.doi.org/10.1016/j.jddst.2022.103625
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author Halevas, Eleftherios
Mavroidi, Barbara
Kokotidou, Chrysoula
Moschona, Alexandra
Sagnou, Marina
Mitraki, Anna
Litsardakis, George
Pelecanou, Maria
author_facet Halevas, Eleftherios
Mavroidi, Barbara
Kokotidou, Chrysoula
Moschona, Alexandra
Sagnou, Marina
Mitraki, Anna
Litsardakis, George
Pelecanou, Maria
author_sort Halevas, Eleftherios
collection PubMed
description Remdesivir is the only clinically available antiviral drug for the treatment of COVID-19. However, its very limited aqueous solubility confines its therapeutic activity and the development of novel inhaled nano-based drug delivery systems of remdesivir for enhanced lung tissue targeting and efficacy is internationally pursued. In this work 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) hyperbranched dendritic nano-scaffolds were employed as nanocarriers of remdesivir. The produced nano-formulations, empty and loaded, consisted of monodisperse nanoparticles with spherical morphology and neutral surface charge and sizes ranging between 80 and 230 nm. The entrapment efficiency and loading capacity of the loaded samples were 82.0% and 14.1%, respectively, whereas the release of the encapsulated drug was complete after 48 h. The toxicity assays in healthy MRC-5 lung diploid fibroblasts and NR8383 alveolar macrophages indicated their suitability as potential remdesivir carriers in the respiratory system. The novel nano-formulations are non-toxic in both tested cell lines, with IC(50) values higher than 400 μΜ after 72 h treatment. Moreover, both free and encapsulated remdesivir exhibited very similar IC(50) values, at the range of 80–90 μM, while its aqueous solubility was increased, overall presenting a suitable profile for application in inhaled delivery of therapeutics.
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spelling pubmed-93646622022-08-10 Remdesivir-loaded bis-MPA hyperbranched dendritic nanocarriers for pulmonary delivery Halevas, Eleftherios Mavroidi, Barbara Kokotidou, Chrysoula Moschona, Alexandra Sagnou, Marina Mitraki, Anna Litsardakis, George Pelecanou, Maria J Drug Deliv Sci Technol Opinion Paper Remdesivir is the only clinically available antiviral drug for the treatment of COVID-19. However, its very limited aqueous solubility confines its therapeutic activity and the development of novel inhaled nano-based drug delivery systems of remdesivir for enhanced lung tissue targeting and efficacy is internationally pursued. In this work 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) hyperbranched dendritic nano-scaffolds were employed as nanocarriers of remdesivir. The produced nano-formulations, empty and loaded, consisted of monodisperse nanoparticles with spherical morphology and neutral surface charge and sizes ranging between 80 and 230 nm. The entrapment efficiency and loading capacity of the loaded samples were 82.0% and 14.1%, respectively, whereas the release of the encapsulated drug was complete after 48 h. The toxicity assays in healthy MRC-5 lung diploid fibroblasts and NR8383 alveolar macrophages indicated their suitability as potential remdesivir carriers in the respiratory system. The novel nano-formulations are non-toxic in both tested cell lines, with IC(50) values higher than 400 μΜ after 72 h treatment. Moreover, both free and encapsulated remdesivir exhibited very similar IC(50) values, at the range of 80–90 μM, while its aqueous solubility was increased, overall presenting a suitable profile for application in inhaled delivery of therapeutics. Elsevier B.V. 2022-09 2022-08-10 /pmc/articles/PMC9364662/ /pubmed/35966803 http://dx.doi.org/10.1016/j.jddst.2022.103625 Text en © 2022 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Opinion Paper
Halevas, Eleftherios
Mavroidi, Barbara
Kokotidou, Chrysoula
Moschona, Alexandra
Sagnou, Marina
Mitraki, Anna
Litsardakis, George
Pelecanou, Maria
Remdesivir-loaded bis-MPA hyperbranched dendritic nanocarriers for pulmonary delivery
title Remdesivir-loaded bis-MPA hyperbranched dendritic nanocarriers for pulmonary delivery
title_full Remdesivir-loaded bis-MPA hyperbranched dendritic nanocarriers for pulmonary delivery
title_fullStr Remdesivir-loaded bis-MPA hyperbranched dendritic nanocarriers for pulmonary delivery
title_full_unstemmed Remdesivir-loaded bis-MPA hyperbranched dendritic nanocarriers for pulmonary delivery
title_short Remdesivir-loaded bis-MPA hyperbranched dendritic nanocarriers for pulmonary delivery
title_sort remdesivir-loaded bis-mpa hyperbranched dendritic nanocarriers for pulmonary delivery
topic Opinion Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364662/
https://www.ncbi.nlm.nih.gov/pubmed/35966803
http://dx.doi.org/10.1016/j.jddst.2022.103625
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