Enhanced dispersibility and deposition of spray-dried powders for pulmonary gene therapy

Hao-Ying Li, Helen Neill, Rebecca Innocent, Peter Seville, Ian Williamson, James C. Birchall*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Spray-drying represents a viable alternative to freeze-drying for preparing dry powder dispersions for delivering macromolecules to the lung. The dispersibility of spray-dried powders is limited however, and needs to be enhanced to improve lung deposition and subsequent biological activity. In this study, we investigate the utility of leucine as a dry powder dispersibility enhancer when added prior to spray-drying a model non-viral gene therapy formulation (lipid:polycation:pDNA, LPD). Freeze-dried lactose-LPD, spray-dried lactose-LPD and spray-dried leucine-lactose-LPD powders were prepared. Scanning electron microscopy showed that leucine, increased the surface roughness of spray-dried lactose particles. Particle size analysis revealed that leucine-containing spray-dried powders were unimodally dispersed with a mean particle diameter of 3.12 μm. Both gel electrophoresis and in vitro cell (A549) transfection showed that leucine may compromise the integrity and biological functionality of the gene therapy vector. The deposition of the leucine containing powder was however significantly enhanced as evidenced by an increase in gene expression mediated by dry powder collected at lower stages of a multistage liquid impinger (MSLI). Further studies are required to determine the potential of leucine as a ubiquitous dispersibility enhancer for a variety of pulmonary formulations. © 2003 Taylor & Francis Ltd.

Original languageEnglish
Pages (from-to)425-432
Number of pages8
JournalJournal of Drug Targeting
Volume11
Issue number7
DOIs
Publication statusPublished - Aug 2003

Keywords

  • leucin
  • LPD complex
  • non-viral gene therapy
  • pulmonary deposition
  • spray-drying

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    Li, H-Y., Neill, H., Innocent, R., Seville, P., Williamson, I., & Birchall, J. C. (2003). Enhanced dispersibility and deposition of spray-dried powders for pulmonary gene therapy. Journal of Drug Targeting, 11(7), 425-432. https://doi.org/10.1080/10611860410001659786