Coarse Spray Delivery to a Localized Region of the Pulmonary Airways for Gene Therapy

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 mu l (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...