Surfactant effects on aerosolized and instilled adenoviral-mediated gene transfer

The effects of surfactant on aerosolization of adenovirus and the distribution of aerosolized and instilled adenovirus in rabbit lungs mere measured. Using Tc-99 sulfur colloid as a marker for the aerosol, P-33-adenovirus with and without H-3-surfactant, we found that the aerosol had the same particle size distribution independent of surfactant and the P-33-adenovirus distributed proportionately to the other radiolabels in the aerosol. Rabbits received aerosolized or instilled suspensions of adenovirus and Tc-99-sulfur colloid with or without 10 mg/ml surfactant. Rabbit lungs were separated into large airways (trachea, carina, and primary bronchi) and more distal lung parenchyma either immediately after treatment for measurement of Tc-99 distribution or 3 days after treatment for luciferase transgene expression, More instillate (94 +/- 1%) than aerosol (68 +/- 2%) was recovered in the parenchyma immediately after treatment (p < 0.01). Transgene expression in the parenchyma as a percent of total lung expression was lower for both instillation (72 +/- 8%) and aerosolization (30 a 8%) than for the initial distributions (p < 0.01). Surfactant did not change the distributions of Tc-99 sulfur colloid or transgene expression. The adenovirus was aerosolized successfully but the distribution of the aerosol did not favor transgene expression in the lung parenchyma.