Inhalable chitosan-based hydrogel as a mucosal adjuvant for hydroxychloroquine in the treatment for SARS-CoV-2 infection in a hamster model.
COVID-19
Chitosan oligosaccharide
Drug inhalation
Hydroxychloroquine
SARS-CoV-2
Journal
Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi
ISSN: 1995-9133
Titre abrégé: J Microbiol Immunol Infect
Pays: England
ID NLM: 100956211
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
02
11
2022
revised:
20
04
2023
accepted:
04
08
2023
pubmed:
25
8
2023
medline:
25
8
2023
entrez:
24
8
2023
Statut:
ppublish
Résumé
Effective therapy for COVID-19 remains limited. Hydroxychloroquine (HCQ) has been considered, but safety and efficacy concerns remain. Chitosan exhibits antiviral and immunomodulatory effects, yet how the combination of HCQ and chitosan performs in treating COVID-19 is unknown. Male Syrian hamsters were inoculated intranasally with standardized stocks of the SARS-CoV-2 virus. Hamsters were allocated to saline (PBS), chitosan oligosaccharide (COS), HCQ, or COS + HCQ groups and received corresponding drugs. On days 1, 7, and 14 post-infection, two animals from each group were euthanized for sample collection. Viral loads were measured in lung homogenates. Biochemistry markers, cytokines, and immunoglobulins were analyzed from hamster sera. HCQ concentrations were compared between the blood, bronchoalveolar lavage, and lung tissues. All groups underwent histopathology exams of the lungs. Additional hamsters were treated with the same drugs to assess for toxicities to the heart and liver. Among all groups, viral loads in the COS + HCQ group were the lowest by day 8. The COS + HCQ group produced the highest interleukin (IL)-6 levels on day 4, and the highest IL-10, IgA and IgG levels on day 8. HCQ concentrations were higher in the COS + HCQ group's lungs than the HCQ group, despite having received half the dose of HCQ. Histopathology demonstrated earlier inflammation resolution and swifter viral clearance in the COS + HCQ group. There was no evidence of cardiac or hepatic injury in hamsters that received HCQ. In hamsters infected with the SARS-CoV-2 virus, the combination of intranasal COS and HCQ was associated with increased HCQ absorption in the lungs, more effective immune responses, without increasing the risk of hepatic or cardiac injuries.
Sections du résumé
BACKGROUND
BACKGROUND
Effective therapy for COVID-19 remains limited. Hydroxychloroquine (HCQ) has been considered, but safety and efficacy concerns remain. Chitosan exhibits antiviral and immunomodulatory effects, yet how the combination of HCQ and chitosan performs in treating COVID-19 is unknown.
METHODS
METHODS
Male Syrian hamsters were inoculated intranasally with standardized stocks of the SARS-CoV-2 virus. Hamsters were allocated to saline (PBS), chitosan oligosaccharide (COS), HCQ, or COS + HCQ groups and received corresponding drugs. On days 1, 7, and 14 post-infection, two animals from each group were euthanized for sample collection. Viral loads were measured in lung homogenates. Biochemistry markers, cytokines, and immunoglobulins were analyzed from hamster sera. HCQ concentrations were compared between the blood, bronchoalveolar lavage, and lung tissues. All groups underwent histopathology exams of the lungs. Additional hamsters were treated with the same drugs to assess for toxicities to the heart and liver.
RESULTS
RESULTS
Among all groups, viral loads in the COS + HCQ group were the lowest by day 8. The COS + HCQ group produced the highest interleukin (IL)-6 levels on day 4, and the highest IL-10, IgA and IgG levels on day 8. HCQ concentrations were higher in the COS + HCQ group's lungs than the HCQ group, despite having received half the dose of HCQ. Histopathology demonstrated earlier inflammation resolution and swifter viral clearance in the COS + HCQ group. There was no evidence of cardiac or hepatic injury in hamsters that received HCQ.
CONCLUSION
CONCLUSIONS
In hamsters infected with the SARS-CoV-2 virus, the combination of intranasal COS and HCQ was associated with increased HCQ absorption in the lungs, more effective immune responses, without increasing the risk of hepatic or cardiac injuries.
Identifiants
pubmed: 37620239
pii: S1684-1182(23)00152-4
doi: 10.1016/j.jmii.2023.08.001
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
951-960Informations de copyright
Copyright © 2023. Published by Elsevier B.V.