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Dry Powder and Nebulized Aerosol Inhalation of Pharmaceuticals Delivered to Mice Using a Nose-only Exposure System
Published on: April 6, 2017
Aerosol Delivery of Polyelectrolyte Surfactant-Antimicrobial Nanoparticles to the Lungs
Yadiel Varela Soler1, Amanda S Padilla-López2,3, Sughosha Rao2
1Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ, 08854, USA.
Background:
Lung infections affect over 80% of adults with cystic fibrosis, with Pseudomonas aeruginosa being a leading pathogen. Although antibiotics are frequently nebulized as standard treatments, the physicochemical environment of the diseased lung often limits their diffusion and overall effectiveness. Our previous studies showed polyelectrolyte surfactants (PS) to be a promising delivery system for cationic antimicrobials in vitro. This study seeks to expand that knowledge by evaluating their potential for nebulized delivery.
Methods:
To achieve this, we evaluated their size and antimicrobial activity following nebulization; in vitro toxicity against epithelial cells and erythrocytes; and biodistribution and expression of inflammation markers following administration to healthy mice.
Results:
The nanoparticle formulation exhibited a mucolytic effect on an artificial mucus model of cystic fibrosis mucus. Following nebulization, nanoparticles retained both their size and biological activity. Additionally, they displayed no observable toxicity in vitro against either human lung epithelial cells or erythrocytes; instead, epithelial cells treated with PS-based nanoparticles showed increased cell viability. Following administration of these formulations to mice via inhalation, over 70% of the recovered nanoparticles were retained in the lungs 24 h after treatment, with a small fraction being uniformly distributed to other tissues. A screen of key inflammatory cytokines revealed that inhalation treatment led to a slight increase of IL-6 in the liver and IL-18 in the spleen. These increases seem to be consistent with a minor inflammatory response.
Conclusion:
Overall, the results suggest that PS are a promising nanotechnology for the pulmonary delivery of cationic drugs.
Insights
Polyelectrolyte surfactants (PS) show promise for nebulized lung drug delivery in cystic fibrosis. Nanoparticles retained size and activity post-nebulization, demonstrating safety and lung retention in mice.
Area of Science:
- Nanotechnology
- Pulmonary drug delivery
- Cystic Fibrosis research
Background:
- Lung infections, particularly Pseudomonas aeruginosa, are prevalent in cystic fibrosis patients.
- Current nebulized antibiotic treatments face limitations due to the lung's physicochemical environment.
- Previous research identified polyelectrolyte surfactants (PS) as effective in vitro delivery systems for cationic antimicrobials.
Purpose of the Study:
- To evaluate the potential of polyelectrolyte surfactants (PS) for nebulized pulmonary drug delivery.
- To assess the characteristics and efficacy of PS nanoparticles after nebulization.
- To determine the safety and biodistribution of PS nanoparticles in vivo.
Main Methods:
- Nebulization of PS nanoparticles, followed by size and antimicrobial activity assessment.
- In vitro toxicity testing on lung epithelial cells and erythrocytes.
- In vivo biodistribution and inflammatory marker analysis in mice after inhalation administration.
Main Results:
- PS nanoparticles demonstrated mucolytic properties and maintained size and activity post-nebulization.
- No in vitro toxicity was observed; increased epithelial cell viability was noted.
- Over 70% of inhaled nanoparticles were retained in mouse lungs after 24 hours, with minimal distribution to other organs.
- A slight, manageable inflammatory response (increased IL-6 and IL-18) was observed in the liver and spleen.
Conclusions:
- Polyelectrolyte surfactants (PS) represent a promising nanotechnology for pulmonary drug delivery.
- The evaluated PS nanoparticles are safe and effective for nebulized administration.
- This approach offers potential for improved treatment of lung infections in cystic fibrosis.
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