Effective nebulization of interferon-γ using a novel vibrating mesh.

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

Reinigung der Verbrennungsabgase bei der Wiederaufarbeitung von HTR-Brennelementen

Experiments on the reprocessing of irradiated thorium-containing HTR fuel elements by the Burn-Leach process (the moderator is burned with oxygen) have been performed in the Hot Cells (HZ-2) of the Kernforschungsanlage Jülich. Results of experiments to purify the off-gases from shaft furnaces and fluidizedbed furnaces are summarized below. The condensable and particulate radioactive nuclides like cesium and zirconium released during the burning process were decontaminated by a factor of 10$^{7}$ by a series of conventional gas purification steps. Their concentrations in the off-gas were reduced to below the MPC values. The system, porous sintered metal filters in the burner followed by an electrostatic filter in the off-gas treatment plant, was demonstrated as an effective method for the separation of these aerosols. Tritium was removed (DF > 10$^{2}$) by molecular sieves or silica gel absorber traps. The release rate of Kr-85 was measured continuously during the burning process. Kr-85 was quantitatively released during the burning of (U,Th)C$_{2}$ fuels. Only about 7 % of the Kr-85 was released during burning of (U,Th)0$_{2}$ fuels irradiated to 10 % fifa. Off-gas concentrations of C-14 and thoron daughter-products were also determined. The design of a large-scale gas purification system for a nuclear fuel reprocessing plant is also discussed