TY - JOUR
T1 - Physical properties, lung deposition modeling, and bioactivity of recombinant GM-CSF aerosolised with a highly efficient nebulizer
AU - Luisetti, Maurizio
AU - Kroneberg, Philipp
AU - Suzuki, Takuji
AU - Kadija, Zamir
AU - Muellinger, Bernhard
AU - Campo, Ilaria
AU - Gleske, Juliane
AU - Rodi, Giuseppe
AU - Zimlich, William C.
AU - Mariani, Francesca
AU - Ferrari, Fabio
AU - Frey, Manuel
AU - Trapnell, Bruce C.
PY - 2011/2
Y1 - 2011/2
N2 - 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 AKITA 2 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 Akita 2 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 AKITA 2 APIXNEB ® nebulizer system is likely to efficaciously deliver rGM-CSF to the airways of patients with autoimmune PAP.
AB - 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 AKITA 2 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 Akita 2 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 AKITA 2 APIXNEB ® nebulizer system is likely to efficaciously deliver rGM-CSF to the airways of patients with autoimmune PAP.
KW - Aerosol delivery of drugs
KW - Modeling of drug deposition
KW - Pulmonary alveolar proteinosis
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U2 - 10.1016/j.pupt.2010.08.004
DO - 10.1016/j.pupt.2010.08.004
M3 - Article
C2 - 20728558
AN - SCOPUS:79251594597
VL - 24
SP - 123
EP - 127
JO - Pulmonary Pharmacology and Therapeutics
JF - Pulmonary Pharmacology and Therapeutics
SN - 1094-5539
IS - 1
ER -