A Potential 3-in-1 Combined AntiSARS-CoV-2 Therapy Using Pulmonary MIL-100(Fe) Formulation

Area of Science:

• Nanomedicine
• Materials Science
• Infectious Diseases

Background:

• The COVID-19 pandemic highlighted critical gaps in global health surveillance and the urgent need for effective antiviral treatments.
• Metal-organic frameworks (MOFs) show promise as drug delivery platforms, but their application in antiviral therapies remains underexplored.
• Existing research on MOFs primarily focuses on sensing applications, with limited exploration in treating infectious diseases.

Purpose of the Study:

• To develop and evaluate a novel, combined 3-in-1 pulmonary multitherapy for COVID-19 using MIL-100(Fe) nanoparticles.
• To investigate the intrinsic antiviral properties of MIL-100(Fe) MOFs combined with favipiravir and heparin for enhanced efficacy.
• To assess the safety, biodistribution, and pulmonary targeting of a mannitol-based microsphere formulation of the MOF nanomedicine.

Main Methods:

• Fabrication of mesoporous iron(III) carboxylate MIL-100(Fe) nanoparticles loaded with favipiravir and surface-functionalized with heparin.
• In vitro assessment of antiviral activity against a COVID-19 infection model, evaluating cellular viability.
• Development of a pulmonary formulation using mannitol-based microspheres and in vivo testing in mice for safety and biodistribution studies.

Main Results:

• The developed MIL-100(Fe)-based nanomedicine demonstrated significant antiviral activity against COVID-19 infection, achieving approximately 70% inhibition while maintaining cellular viability.
• The pulmonary formulation exhibited favorable safety profiles in mice, with no significant adverse effects observed.
• Biodistribution studies confirmed successful delivery to the deep lungs, indicating a reduced immunological response compared to control groups.

Conclusions:

• The novel MIL-100(Fe)-based nanomedicine offers a promising 3-in-1 pulmonary multitherapy for COVID-19 with significant antiviral efficacy and a good safety profile.
• The successful pulmonary delivery and reduced immunological response highlight the potential of customized MOF platforms for challenging infectious and pulmonary diseases.
• These findings support further preclinical and clinical investigations for advanced therapeutic MOF applications in respiratory infections.