Physical properties, lung deposition modeling, and bioactivity of recombinant GM-CSF aerosolised with a highly efficient nebulizer

Maurizio Luisetti, Philipp Kroneberg, Takuji Suzuki, Zamir Kadija, Bernhard Muellinger, Ilaria Campo, Juliane Gleske, Giuseppe Rodi, William C. Zimlich, Francesca Mariani, Fabio Ferrari, Manuel Frey, Bruce C. Trapnell

Research output: Contribution to journalArticle

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 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.

Original languageEnglish
Pages (from-to)123-127
Number of pages5
JournalPulmonary Pharmacology and Therapeutics
Volume24
Issue number1
DOIs
Publication statusPublished - Feb 2011

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Keywords

  • Aerosol delivery of drugs
  • Modeling of drug deposition
  • Pulmonary alveolar proteinosis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Pharmacology (medical)
  • Biochemistry, medical

Cite this

Luisetti, M., Kroneberg, P., Suzuki, T., Kadija, Z., Muellinger, B., Campo, I., Gleske, J., Rodi, G., Zimlich, W. C., Mariani, F., Ferrari, F., Frey, M., & Trapnell, B. C. (2011). Physical properties, lung deposition modeling, and bioactivity of recombinant GM-CSF aerosolised with a highly efficient nebulizer. Pulmonary Pharmacology and Therapeutics, 24(1), 123-127. https://doi.org/10.1016/j.pupt.2010.08.004