Cargando…

Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19

The coronavirus disease 2019 (COVID-19) is an unprecedented pandemic that has severely impacted global public health and the economy. Hydroxychloroquine administered orally to COVID-19 patients was ineffective, but its antiviral and anti-inflammatory actions were observed in vitro. The lack of effic...

Descripción completa

Detalles Bibliográficos
Autores principales: Tai, Waiting, Chow, Michael Yee Tak, Chang, Rachel Yoon Kyung, Tang, Patricia, Gonda, Igor, MacArthur, Robert B., Chan, Hak-Kim, Kwok, Philip Chi Lip
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399722/
https://www.ncbi.nlm.nih.gov/pubmed/34452220
http://dx.doi.org/10.3390/pharmaceutics13081260
_version_ 1783745145964855296
author Tai, Waiting
Chow, Michael Yee Tak
Chang, Rachel Yoon Kyung
Tang, Patricia
Gonda, Igor
MacArthur, Robert B.
Chan, Hak-Kim
Kwok, Philip Chi Lip
author_facet Tai, Waiting
Chow, Michael Yee Tak
Chang, Rachel Yoon Kyung
Tang, Patricia
Gonda, Igor
MacArthur, Robert B.
Chan, Hak-Kim
Kwok, Philip Chi Lip
author_sort Tai, Waiting
collection PubMed
description The coronavirus disease 2019 (COVID-19) is an unprecedented pandemic that has severely impacted global public health and the economy. Hydroxychloroquine administered orally to COVID-19 patients was ineffective, but its antiviral and anti-inflammatory actions were observed in vitro. The lack of efficacy in vivo could be due to the inefficiency of the oral route in attaining high drug concentration in the lungs. Delivering hydroxychloroquine by inhalation may be a promising alternative for direct targeting with minimal systemic exposure. This paper reports on the characterisation of isotonic, pH-neutral hydroxychloroquine sulphate (HCQS) solutions for nebulisation for COVID-19. They can be prepared, sterilised, and nebulised for testing as an investigational new drug for treating this infection. The 20, 50, and 100 mg/mL HCQS solutions were stable for at least 15 days without refrigeration when stored in darkness. They were atomised from Aerogen Solo Ultra vibrating mesh nebulisers (1 mL of each of the three concentrations and, in addition, 1.5 mL of 100 mg/mL) to form droplets having a median volumetric diameter of 4.3–5.2 µm, with about 50–60% of the aerosol by volume < 5 µm. The aerosol droplet size decreased (from 4.95 to 4.34 µm) with increasing drug concentration (from 20 to 100 mg/mL). As the drug concentration and liquid volume increased, the nebulisation duration increased from 3 to 11 min. The emitted doses ranged from 9.1 to 75.9 mg, depending on the concentration and volume nebulised. The HCQS solutions appear suitable for preclinical and clinical studies for potential COVID-19 treatment.
format Online
Article
Text
id pubmed-8399722
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-83997222021-08-29 Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19 Tai, Waiting Chow, Michael Yee Tak Chang, Rachel Yoon Kyung Tang, Patricia Gonda, Igor MacArthur, Robert B. Chan, Hak-Kim Kwok, Philip Chi Lip Pharmaceutics Article The coronavirus disease 2019 (COVID-19) is an unprecedented pandemic that has severely impacted global public health and the economy. Hydroxychloroquine administered orally to COVID-19 patients was ineffective, but its antiviral and anti-inflammatory actions were observed in vitro. The lack of efficacy in vivo could be due to the inefficiency of the oral route in attaining high drug concentration in the lungs. Delivering hydroxychloroquine by inhalation may be a promising alternative for direct targeting with minimal systemic exposure. This paper reports on the characterisation of isotonic, pH-neutral hydroxychloroquine sulphate (HCQS) solutions for nebulisation for COVID-19. They can be prepared, sterilised, and nebulised for testing as an investigational new drug for treating this infection. The 20, 50, and 100 mg/mL HCQS solutions were stable for at least 15 days without refrigeration when stored in darkness. They were atomised from Aerogen Solo Ultra vibrating mesh nebulisers (1 mL of each of the three concentrations and, in addition, 1.5 mL of 100 mg/mL) to form droplets having a median volumetric diameter of 4.3–5.2 µm, with about 50–60% of the aerosol by volume < 5 µm. The aerosol droplet size decreased (from 4.95 to 4.34 µm) with increasing drug concentration (from 20 to 100 mg/mL). As the drug concentration and liquid volume increased, the nebulisation duration increased from 3 to 11 min. The emitted doses ranged from 9.1 to 75.9 mg, depending on the concentration and volume nebulised. The HCQS solutions appear suitable for preclinical and clinical studies for potential COVID-19 treatment. MDPI 2021-08-14 /pmc/articles/PMC8399722/ /pubmed/34452220 http://dx.doi.org/10.3390/pharmaceutics13081260 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tai, Waiting
Chow, Michael Yee Tak
Chang, Rachel Yoon Kyung
Tang, Patricia
Gonda, Igor
MacArthur, Robert B.
Chan, Hak-Kim
Kwok, Philip Chi Lip
Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19
title Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19
title_full Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19
title_fullStr Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19
title_full_unstemmed Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19
title_short Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19
title_sort nebulised isotonic hydroxychloroquine aerosols for potential treatment of covid-19
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399722/
https://www.ncbi.nlm.nih.gov/pubmed/34452220
http://dx.doi.org/10.3390/pharmaceutics13081260
work_keys_str_mv AT taiwaiting nebulisedisotonichydroxychloroquineaerosolsforpotentialtreatmentofcovid19
AT chowmichaelyeetak nebulisedisotonichydroxychloroquineaerosolsforpotentialtreatmentofcovid19
AT changrachelyoonkyung nebulisedisotonichydroxychloroquineaerosolsforpotentialtreatmentofcovid19
AT tangpatricia nebulisedisotonichydroxychloroquineaerosolsforpotentialtreatmentofcovid19
AT gondaigor nebulisedisotonichydroxychloroquineaerosolsforpotentialtreatmentofcovid19
AT macarthurrobertb nebulisedisotonichydroxychloroquineaerosolsforpotentialtreatmentofcovid19
AT chanhakkim nebulisedisotonichydroxychloroquineaerosolsforpotentialtreatmentofcovid19
AT kwokphilipchilip nebulisedisotonichydroxychloroquineaerosolsforpotentialtreatmentofcovid19