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Published on: February 20, 2019
Effective nebulization of interferon-γ using a novel vibrating mesh
Louise Sweeney1,2, Alice P McCloskey2,3,4, Gerard Higgins2,3,4
1Aerogen, IDA Business Park, Dangan, Galway, Ireland.
Interferon gamma (IFN-γ) can be effectively nebulized using vibrating mesh nebulizers, maintaining its stability and bioactivity. A new mesh technology (PDAP) offers improved aerosol properties for enhanced lung delivery of IFN-γ.
Area of Science:
- Pulmonary Drug Delivery
- Biotechnology
- Respiratory Medicine
Background:
- Interferon gamma (IFN-γ) is a key immunomodulatory cytokine with therapeutic potential for respiratory diseases like tuberculosis and pulmonary fibrosis.
- Effective aerosol delivery of IFN-γ to the lungs is crucial for clinical translation but faces challenges with stability and delivery systems.
- Vibrating mesh nebulizers offer a promising approach for targeted aerosol delivery of large biomolecules like IFN-γ.
Purpose of the Study:
- To evaluate the efficacy of nebulizing IFN-γ using two distinct vibrating mesh nebulizer technologies with different mesh architectures.
- To compare the aerosol characteristics and bioactivity of IFN-γ post-nebulization.
- To assess the potential of these nebulizers for efficient delivery of therapeutically active IFN-γ to the lower respiratory tract.
Main Methods:
- Nebulization of IFN-γ was performed using two vibrating mesh nebulizer types: Aerogen Solo® (standard) and Photo-defined aperture plate (PDAP®) (new iteration).
- Comprehensive aerosol studies included aerosol output, droplet size analysis (MMAD, VMD), and aerosol therapy assessments.
- Post-nebulization IFN-γ stability and bioactivity were confirmed via SDS-PAGE and assessment of IP-10 expression in THP-1 derived macrophages.
Main Results:
- Both vibrating mesh technologies demonstrated high emitted doses of aerosolized IFN-γ (≥93%).
- The PDAP device generated smaller droplet sizes (MMAD: 2.79 ± 0.29 μm; VMD: 2.33 ± 0.02 μm) compared to the Solo device (MMAD: 4.39 ± 0.25 μm; VMD: 4.30 ± 0.02 μm).
- SDS-PAGE and bioactivity assays confirmed that nebulization did not compromise IFN-γ stability or its ability to induce IP-10 expression.
Conclusions:
- Vibrating mesh nebulizer devices can effectively nebulize IFN-γ without compromising its stability or bioactivity.
- The PDAP technology offers superior aerodynamic properties for IFN-γ aerosols, potentially enhancing lower respiratory tract deposition.
- This aerosolization method represents a viable strategy for advancing the clinical application of inhaled IFN-γ.
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