Physical Properties, Lung Deposition Modeling, And Bioactivity Of Recombinant Gm-Csf Aerosolised With A Highly Efficient Nebulizer
Résumé
Pulmonary alveolar proteinosis (PAP) is a rare condition characterized by the accumulation of lipoproteinaceous material within air spaces. Although whole lung lavage is the current standard of care, recent advances in our understanding of PAP pathophysiology suggest that the disorder may benefit from inhalation of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF). The aim of this study was to determine the physical properties and bioactivity of rGM-CSF aerosolized by the highly efficient AKITA APIXNEB® nebulizer system. The physical properties of aerosolised rGM-CSF were investigated in terms of droplet size, output and output rate by laser diffraction and gravimetrical analysis. Lung deposition was assessed using deposition modeling (ICRP). Molecular mass before and after aerosolisation was determined by SDS-PAGE, while the bioactivity of rGM-CSF was evaluated by measuring the GM-CSF-stimulated increase in pSTAT-5 using mAM-hGM-R cells. Ninety-six % of the rGM-CSF filling dose was aerosolized with the Akita Apixneb® nebulizer system. Particle size was highly reproducible, and the amount deposited within the lung was 80.35% of the delivered dose. The aerosolisation did not alter the molecular structure of rGM-CSF, nor its ability to stimulate the pSTAT-5, which increased by 99.5%, similar to values for rGM-CSF prior to aerosolisation. We conclude that the highly efficient AKITA APIXNEB® nebulizer system is likely to efficaciously deliver rGM-CSF to the airways of patients with autoimmune PAP.
Domaines
Pneumologie et système respiratoire
Origine : Fichiers produits par l'(les) auteur(s)
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