>>AAPS PharmSci 2002;4(3):E13
Aerosolization of lipoplexes using AERx Pulmonary Delivery System.
Deshpande D, Blanchard J, Srinivasan S, Fairbanks D, Fujimoto J, Sawa T, Wiener-Kronish J, Schreier H, Gonda I.
Aradigm Corporation, 3929 Point Eden Way, Hayward, CA 94545, USA. deshpanded@aradigm.com
The lung represents an attractive target for delivering gene therapy to achieve local and potentially systemic delivery of gene products. The objective of this study was to evaluate the feasibility of the AERx Pulmonary Delivery System for delivering nonviral gene therapy formulations to the lung. We found that "naked" DNA undergoes degradation following aerosolization through the AERx nozzle system. However, DNA formulated with a molar excess of cationic lipids (lipoplexes) showed no loss of integrity. In addition, the lipoplexes showed no significant change in particle size, zeta (zeta) potential, or degree of complexation following extrusion. The data suggest that complexation with cationic lipids had a protective effect on the formulation following extrusion. In addition, there was no significant change in the potency of the formulation as determined by a transfection study in A-549 cells in culture. We also found that DNA formulations prepared in lactose were aerosolized poorly. Significant improvements in aerosolization efficiency were seen when electrolytes such as NaCl were added to the formulation. In conclusion, the data suggest that delivery of lipoplexes using the AERx Pulmonary Delivery System may be a viable approach for pulmonary gene therapy.<<
Cheers, Tuck |
