Effective nebulization of interferon-γ using a novel vibrating mesh
Abstract Background Interferon gamma (IFN-γ) is a clinically relevant immunomodulatory cytokine that has demonstrated significant potential in the treatment and management of respiratory diseases such as tuberculosis and pulmonary fibrosis. As with all large biomolecules, clinical translation is dep...
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doaj-6a2830aa51674b6aab4f31fd62ea27872020-11-25T02:29:21ZengBMCRespiratory Research1465-993X2019-04-0120111110.1186/s12931-019-1030-1Effective nebulization of interferon-γ using a novel vibrating meshLouise Sweeney0Alice P. McCloskey1Gerard Higgins2Joanne M. Ramsey3Sally-Ann Cryan4Ronan MacLoughlin5Aerogen, IDA Business Park, DanganSchool of Pharmacy, RCSISchool of Pharmacy, RCSISchool of Pharmacy, RCSISchool of Pharmacy, RCSIAerogen, IDA Business Park, DanganAbstract Background Interferon gamma (IFN-γ) is a clinically relevant immunomodulatory cytokine that has demonstrated significant potential in the treatment and management of respiratory diseases such as tuberculosis and pulmonary fibrosis. As with all large biomolecules, clinical translation is dependent on effective delivery to the disease site and delivery of IFN-γ as an aerosol offers a logical means of drug targeting. Effective localization is often hampered by instability and a lack of safe and efficient delivery systems. The present study sought to determine how effectively IFN-γ can be nebulized using two types of vibrating mesh nebulizer, each with differing mesh architectures, and to investigate the comparative efficiency of delivery of therapeutically active IFN-γ to the lungs. Methods Nebulization of IFN-γ was carried out using two different Aerogen vibrating mesh technologies with differing mesh architectures. These technologies represent both a standard commercially available mesh type (Aerogen Solo®) and a new iteration mesh (Photo-defined aperture plate (PDAP®). Extensive aerosol studies (aerosol output and droplet analysis, non-invasive and invasive aerosol therapy) were conducted in line with regulatory requirements and characterization of the stability and bioactivity of the IFN-γ post-nebulization was confirmed using SDS-PAGE and stimulation of Human C-X-C motif chemokine 10 (CXCL 10) also known as IFN-γ-induced protein 10KDa (IP 10) expression from THP-1 derived macrophages (THP-1 cells). Results Aerosol characterization studies indicated that a significant and reproducible dose of aerosolized IFN-γ can be delivered using both vibrating mesh technologies. Nebulization using both devices resulted in an emitted dose of at least 93% (100% dose minus residual volume) for IFN-γ. Characterization of aerosolized IFN-γ indicated that the PDAP was capable of generating droplets with a significantly lower mass median aerodynamic diameter (MMAD) with values of 2.79 ± 0.29 μm and 4.39 ± 0.25 μm for the PDAP and Solo respectively. The volume median diameters (VMD) of aerosolized IFN-γ corroborated this with VMDs of 2.33 ± 0.02 μm for the PDAP and 4.30 ± 0.02 μm for the Solo. SDS-PAGE gels indicated that IFN-γ remains stable after nebulization by both devices and this was confirmed by bioactivity studies using a THP-1 cell model in which an alveolar macrophage response to IFN-γ was determined. IFN-γ nebulized by the PDAP and Solo devices had no significant effect on the key inflammatory biomarker cytokine IP-10 release from this model in comparison to non-nebulized controls. Here we demonstrate that it is possible to combine IFN-γ with vibrating mesh nebulizer devices and facilitate effective aerosolisation with minimal impact on IFN-γ structure or bioactivity. Conclusions It is possible to nebulize IFN-γ effectively with vibrating mesh nebulizer devices without compromising its stability. The PDAP allows for generation of IFN-γ aerosols with improved aerodynamic properties thereby increasing its potential efficiency for lower respiratory tract deposition over current technology, whilst maintaining the integrity and bioactivity of IFN-γ. This delivery modality therefore offers a rational means of facilitating the clinical translation of inhaled IFN-γ.http://link.springer.com/article/10.1186/s12931-019-1030-1Idiopathic pulmonary fibrosisTuberculosisInterferon gammaInhaled therapyVibrating meshNebulizer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Louise Sweeney Alice P. McCloskey Gerard Higgins Joanne M. Ramsey Sally-Ann Cryan Ronan MacLoughlin |
spellingShingle |
Louise Sweeney Alice P. McCloskey Gerard Higgins Joanne M. Ramsey Sally-Ann Cryan Ronan MacLoughlin Effective nebulization of interferon-γ using a novel vibrating mesh Respiratory Research Idiopathic pulmonary fibrosis Tuberculosis Interferon gamma Inhaled therapy Vibrating mesh Nebulizer |
author_facet |
Louise Sweeney Alice P. McCloskey Gerard Higgins Joanne M. Ramsey Sally-Ann Cryan Ronan MacLoughlin |
author_sort |
Louise Sweeney |
title |
Effective nebulization of interferon-γ using a novel vibrating mesh |
title_short |
Effective nebulization of interferon-γ using a novel vibrating mesh |
title_full |
Effective nebulization of interferon-γ using a novel vibrating mesh |
title_fullStr |
Effective nebulization of interferon-γ using a novel vibrating mesh |
title_full_unstemmed |
Effective nebulization of interferon-γ using a novel vibrating mesh |
title_sort |
effective nebulization of interferon-γ using a novel vibrating mesh |
publisher |
BMC |
series |
Respiratory Research |
issn |
1465-993X |
publishDate |
2019-04-01 |
description |
Abstract Background Interferon gamma (IFN-γ) is a clinically relevant immunomodulatory cytokine that has demonstrated significant potential in the treatment and management of respiratory diseases such as tuberculosis and pulmonary fibrosis. As with all large biomolecules, clinical translation is dependent on effective delivery to the disease site and delivery of IFN-γ as an aerosol offers a logical means of drug targeting. Effective localization is often hampered by instability and a lack of safe and efficient delivery systems. The present study sought to determine how effectively IFN-γ can be nebulized using two types of vibrating mesh nebulizer, each with differing mesh architectures, and to investigate the comparative efficiency of delivery of therapeutically active IFN-γ to the lungs. Methods Nebulization of IFN-γ was carried out using two different Aerogen vibrating mesh technologies with differing mesh architectures. These technologies represent both a standard commercially available mesh type (Aerogen Solo®) and a new iteration mesh (Photo-defined aperture plate (PDAP®). Extensive aerosol studies (aerosol output and droplet analysis, non-invasive and invasive aerosol therapy) were conducted in line with regulatory requirements and characterization of the stability and bioactivity of the IFN-γ post-nebulization was confirmed using SDS-PAGE and stimulation of Human C-X-C motif chemokine 10 (CXCL 10) also known as IFN-γ-induced protein 10KDa (IP 10) expression from THP-1 derived macrophages (THP-1 cells). Results Aerosol characterization studies indicated that a significant and reproducible dose of aerosolized IFN-γ can be delivered using both vibrating mesh technologies. Nebulization using both devices resulted in an emitted dose of at least 93% (100% dose minus residual volume) for IFN-γ. Characterization of aerosolized IFN-γ indicated that the PDAP was capable of generating droplets with a significantly lower mass median aerodynamic diameter (MMAD) with values of 2.79 ± 0.29 μm and 4.39 ± 0.25 μm for the PDAP and Solo respectively. The volume median diameters (VMD) of aerosolized IFN-γ corroborated this with VMDs of 2.33 ± 0.02 μm for the PDAP and 4.30 ± 0.02 μm for the Solo. SDS-PAGE gels indicated that IFN-γ remains stable after nebulization by both devices and this was confirmed by bioactivity studies using a THP-1 cell model in which an alveolar macrophage response to IFN-γ was determined. IFN-γ nebulized by the PDAP and Solo devices had no significant effect on the key inflammatory biomarker cytokine IP-10 release from this model in comparison to non-nebulized controls. Here we demonstrate that it is possible to combine IFN-γ with vibrating mesh nebulizer devices and facilitate effective aerosolisation with minimal impact on IFN-γ structure or bioactivity. Conclusions It is possible to nebulize IFN-γ effectively with vibrating mesh nebulizer devices without compromising its stability. The PDAP allows for generation of IFN-γ aerosols with improved aerodynamic properties thereby increasing its potential efficiency for lower respiratory tract deposition over current technology, whilst maintaining the integrity and bioactivity of IFN-γ. This delivery modality therefore offers a rational means of facilitating the clinical translation of inhaled IFN-γ. |
topic |
Idiopathic pulmonary fibrosis Tuberculosis Interferon gamma Inhaled therapy Vibrating mesh Nebulizer |
url |
http://link.springer.com/article/10.1186/s12931-019-1030-1 |
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