Coarse spray delivery to a localized region of the pulmonary airways for gene therapy. Academic Article uri icon

Overview

MeSH

  • Administration, Inhalation
  • Aerosols
  • Cell Line
  • Cystic Fibrosis
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Dose-Response Relationship, Drug
  • Humans
  • Models, Anatomic
  • Particle Size
  • Technetium Tc 99m Sulfur Colloid

MeSH Major

  • Adenoviridae
  • Gene Transfer Techniques
  • Genetic Therapy
  • Genetic Vectors
  • Lung

abstract

  • Targeting adenoviral vectors for cystic fibrosis gene therapy to the human airways with minimal exposure to alveoli would avoid adverse reactions and maximize response. At present, to deliver gene therapy vectors, large volumes of fluid are instilled or nebulized as aerosols. Either approach would likely cause alveolar exposure and increases the potential for side effects. We describe a coarse spray delivery device that precisely and reproducibly delivers the viral vector to the human airways to treat a small region of the airways for clinical trials. An endoscopic washing pipe (Olympus) that can be inserted into the channel of a bronchoscope was used. To minimize the escape of the therapeutic material downstream from the site of administration, we restricted the volume delivered to <150 microl (to prevent bulk flow), and used large droplets. Their high velocity further enhanced the probability of impaction in the vicinity of the nozzle. A pneumatic dosing system (Kahnetics) was used to reproducibly deliver the spray. The droplet size distribution was determined by laser diffraction and confirmed by cascade impaction: 190-microm volume median diameter with 1% mass <10 microm. The localization of the spray was studied in hollow cast models of human airways. 99mTc-sulfur colloid was used as a radiolabeled marker for these studies. Localization of the deposited spray was determined by scintigraphy and by measuring the radioactivity exiting the terminal airways. In the lung casts the spray was localized to one or two generations over an approximately 2-cm2 area. We conclude that delivery of large droplet sprays limits exposure to a few generations and may be useful in topical gene delivery clinical trials.

publication date

  • January 20, 2000

has subject area

  • Adenoviridae
  • Administration, Inhalation
  • Aerosols
  • Cell Line
  • Cystic Fibrosis
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Dose-Response Relationship, Drug
  • Gene Transfer Techniques
  • Genetic Therapy
  • Genetic Vectors
  • Humans
  • Lung
  • Models, Anatomic
  • Particle Size
  • Technetium Tc 99m Sulfur Colloid

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1089/10430340050016085

PubMed ID

  • 10680848

Additional Document Info

start page

  • 361

end page

  • 371

volume

  • 11

number

  • 2