Inhalable chitosan-based hydrogel as a mucosal adjuvant for hydroxychloroquine in the treatment for SARS-CoV-2 infection in a hamster model

Donna Shu-Han Lin; Shian Chiuan Tzeng; Tai-Lung Cha; Chin-Mao Hung; Wen-Chin Lin; Chuen-Mi Yang; Hsuan-Ying Lu; Jia-Yu Chang; Shu-Wei Huang

doi:10.1016/j.jmii.2023.08.001

Inhalable chitosan-based hydrogel as a mucosal adjuvant for hydroxychloroquine in the treatment for SARS-CoV-2 infection in a hamster model

J Microbiol Immunol Infect. 2023 Oct;56(5):951-960. doi: 10.1016/j.jmii.2023.08.001. Epub 2023 Aug 15.

Authors

Donna Shu-Han Lin¹, Shian Chiuan Tzeng², Tai-Lung Cha³, Chin-Mao Hung³, Wen-Chin Lin⁴, Chuen-Mi Yang³, Hsuan-Ying Lu³, Jia-Yu Chang³, Shu-Wei Huang⁵

Affiliations

¹ Division of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
² Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan.
³ Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan.
⁴ Institute of Preventive Medicine, National Defense Medical Center, Taipei, Taiwan; Department of Pathology and Graduate Institute of Pathology and Parasitology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
⁵ Department of Orthopedics, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: judyya1022@gmail.com.

PMID: 37620239
DOI: 10.1016/j.jmii.2023.08.001

Abstract

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: 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: 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: 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.

Keywords: COVID-19; Chitosan oligosaccharide; Drug inhalation; Hydroxychloroquine; SARS-CoV-2.