Aerosolization of lipoplexes using AERx® pulmonary delivery system
Journal Title: The AAPS Journal - Year 2002, Vol 4, Issue 3
Abstract
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 (ζ) 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.
Authors and Affiliations
Deepa Deshpande, James Blanchard, Sudarshan Srinivasan, Dallas Fairbanks, Jun Fujimoto, Teiji Sawa, Jeanine Wiener-Kronish, Hans Schreier, Igor Gonda
Keywords
Related Articles
- EP ID EP682003
- DOI 10.1208/ps040313
- Views 106
- Downloads 0
Is any measurement method optimal for all aggregate sizes and types?
Protein-based pharmaceuticals exhibit a wide range of aggregation phenomena, making it virtually impossible to find any one analytical method that works well in all cases. Aggregate sizes cover a range from small oligome...
Population Pharmacokinetics and Pharmacodynamics of Ribavirin in Patients with Chronic Hepatitis C Genotype 1 Infection
We report a population pharmacokinetic (PK) and pharmacodynamic (PD) model of orally administered ribavirin in patients with chronic hepatitis C virus (HCV) infection enrolled in a multicenter clinical trial, including t...
Early Engineering Approaches to Improve Peptide Developability and Manufacturability
Downstream success in Pharmaceutical Development requires thoughtful molecule design early in the lifetime of any potential therapeutic. Most therapeutic monoclonal antibodies are quite similar with respect to their deve...
Viewing chemokines as a third major system of communication in the brain
There is irrefutable proof that opioids and other classes of centrally acting drugs have profound effects on the immune system. Evidence is mounting that products of the immune system, such as chemokines, can reciprocall...
Solid Lipid Particles for Oral Delivery of Peptide and Protein Drugs III — the Effect of Fed State Conditions on the In Vitro Release and Degradation of Desmopressin
The effect of food intake on the release and degradation of peptide drugs from solid lipid particles is unknown and was therefore investigated in vitro using different fed state media in a lipolysis model. Desmopressin w...