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 were measured. Using 99Tc sulfur colloid as a marker for the aerosol, 33P-adenovirus with and without 3H-surfactant, we found that the aerosol had the same particle size distribution independent of surfactant and the 33P-adenovirus distributed proportionately to the other radiolabels in the aerosol. Rabbits received aerosolized or instilled suspensions of adenovirus and 99Tc-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 99Tc 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 +/- 8%) than for the initial distributions (p < 0.01). Surfactant did not change the distributions of 99Tc 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.
Jobe
A H
AH
Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA 90509-2910, USA.
Ikegami
M
M
Yei
S
S
Whitsett
J A
JA
Trapnell
B
B
D000260:Adenoviruses, Human / Q000235:genetics*; D000336:Aerosols; D000818:Animals; D001688:Biological Products; D005260:Female; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007322:Instillation, Drug; D008156:Luciferases / Q000235:genetics; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D011817:Rabbits
D000336:Aerosols; D001688:Biological Products; D011663:Pulmonary Surfactants; D008156:Luciferases; C072197:beractant