title: Physical properties, lung deposition modeling, and bioactivity of recombinant GM-CSF aerosolised with a highly efficient nebulizer.
abstract: 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 aerosolised by the highly efficient AKITA² 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 pSTAT5 using mAM-hGM-R cells. Ninety-six % of the rGM-CSF filling dose was aerosolised with the Akita² 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 pSTAT5, which increased by 99.5%, similar to values for rGM-CSF prior to aerosolisation. We conclude that the highly efficient AKITA² APIXNEB® nebulizer system is likely to efficaciously deliver rGM-CSF to the airways of patients with autoimmune PAP.
authors: Laboratory of Biochemistry and Genetics, Respiratory Disease Unit, IRCCS San Matteo Hospital Foundation & University of Pavia, Italy. m.luisetti@smatteo.pv.it
authors: Maurizio
authors: M
authors: Luisetti
authors: Philipp
authors: P
authors: Kroneberg
authors: Takuji
authors: T
authors: Suzuki
authors: Zamir
authors: Z
authors: Kadija
authors: Bernhard
authors: B
authors: Muellinger
authors: Ilaria
authors: I
authors: Campo
authors: Juliane
authors: J
authors: Gleske
authors: Giuseppe
authors: G
authors: Rodi
authors: William C
authors: WC
authors: Zimlich
authors: Francesca
authors: F
authors: Mariani
authors: Fabio
authors: F
authors: Ferrari
authors: Manuel
authors: M
authors: Frey
authors: Bruce C
authors: BC
authors: Trapnell
mesh_terms: D000336:Aerosols; D000818:Animals; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D051379:Mice; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011649:Pulmonary Alveolar Proteinosis / Q000188:drug therapy*; D011994:Recombinant Proteins
chemical_list: D000336:Aerosols; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor