In patients with idiopathic pulmonary fibrosis (IPF), treatment with interferon beta (IFN-β) delivered through a mesh nebulizer is associated with decreased fibroblast proliferation, according to a study published in the Journal of Aerosol Medicine and Pulmonary Drug Delivery.

Among individuals with IPF, delivery of IFN-β via intravenous or subcutaneous injection has not been associated with improved overall survival. A nebulizer delivery system aerosolizes liquid medications, thus allowing deeper penetration and deposition in the lungs.

Nebulizers are divided into 3 types, based on their operational mechanisms: jet nebulizers, ultrasonic nebulizers, and vibrating mesh nebulizers. Mesh nebulizers, the newest type, use a mesh membrane containing thousands of small pores, which generates a fine mist that can be inhaled deeply and deposited into an individual’s lungs.


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The researchers in this study used a breathing simulator to evaluate the efficiency of delivery of IFN-β, along with a thermocouple during the actual nebulization to monitor the temperature, in order to compare the 3 different types of nebulizers.

Bleomycin (BLM)- or transforming growth factor beta (TGF-β)-treated human lung fibroblast (HLF) cells were used to assess the antifibrotic activity of IFN-β pre- and postnebulization. A 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was used to measure cell viability. Cell migration and myofibroblast differentiation ability were evaluated via Transwell migration assay and quantitative polymerase chain reaction analysis, respectively.

Results of the study revealed that the structural integrity and biological function of nebulized IFN-β were not compromised with the mesh nebulization method of delivery. The mean particle size by volume (DV50) value obtained with the mesh nebulizer was 4.019 μm—a value within the 1- to 5-μm respirable range. The mean DV50 values with the jet and ultrasonic nebulizers, in contrast, were above the respirable range (5.491 μm and 5.433 μm, respectively). In addition, the fine particle fraction for the mesh nebulizer was higher than the respective values for the other 2 devices.

The delivered dose from the 3 types of nebulizers was evaluated with a breathing simulator and quantified with the use of high-performance liquid chromatography. The 3 different types of nebulizers and HLF cells were used to analyze the therapeutic effects of nebulized IFN-β on lung fibrosis.

Of note, the mesh nebulizer increased the therapeutic effects of IFN-β on HLF cells. In contrast, IFN-β nebulized with the jet and ultrasonic nebulizers decreased the effects of IFN-β on suppression of HLF cell proliferation.

“The development of new inhalation treatments for IPF is indispensable to offer new alternatives to patients with this condition,” they authors highlighted. “[T]he findings indicated that the deposition of IFN-β delivered through mesh technology in the lungs might outperform that achieved through jet and ultrasonic technologies, based on the aerosol particle size distribution and stability,” they concluded.

Utilization of the mesh technology has led to the delivery of a wider range of medications with enhanced efficiency of drug delivery, requiring droplet sizes in the respirable range of 1 to 5 μm in diameter, along with decreased residual volume. Additional benefits of mesh nebulizers include their quiet operation and portability.

Reference

Cuevas Brun EH, Hong Z-Y, Hsu Y-M, et al. Stability and activity of interferon beta to treat idiopathic pulmonary fibrosis with different nebulizer technologies. J Aerosol Med Pulm Drug Deliv. Published online February 23, 2023. doi:10.1089/jamp.2022.0020