Nebulization of biodegradable nanoparticles: impact of nebulizer technology and nanoparticle characteristics on aerosol features

• Published in: Journal of controlled release 2003-01, Vol.86 (1), p.131-144
• Main Authors: Dailey, Lea Ann, Schmehl, Thomas, Gessler, Tobias, Wittmar, Matthias, Grimminger, Friedrich, Seeger, Werner, Kissel, Thomas
• Format: Article
• Language: English
• Subjects: Aerosol; Aerosols - chemistry; Biological and medical sciences; General pharmacology; Medical sciences; Microspheres; Nanoparticle; Nanotechnology - methods; Nanotechnology - statistics & numerical data; Nebulizer; Nebulizers and Vaporizers - standards; Nebulizers and Vaporizers - statistics & numerical data; Particle size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Suspension
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/S0168-3659(02)00370-X

Nanoparticles may be effective drug delivery systems for use in various pulmonary therapeutic schemes. This study investigated the effect of nebulization technology and nanoparticle characteristics on the features of aerosol generation. Suspensions of biodegradable nanoparticles consisting of commercially available poly(lactide-co-glycolide) and novel comb polymers were nebulized with a jet, ultrasonic, and piezo-electric crystal nebulizer. The effects of the nanoparticle suspensions on the aerosol droplet size, as well as the nanoparticle size before and after nebulization, were characterized via laser diffraction. While the individual nanoparticle suspensions showed no clinically relevant influence on aerosol droplet size, as compared to control experiments, an enhanced nanoparticle aggregation within the droplets was observed. This aggregation was further characterized by fluorescence and scanning electron microscopy. Dependency of aggregation on nebulizer technology and nanoparticle characteristics was noted. Nanoparticles exhibiting the highest surface hydrophobicity were particularly susceptible to aggregation when nebulized with a jet nebulizer. Aggregation was reduced with nanoparticles exhibiting a more hydrophilic surface or when using ultrasonic nebulizers. We conclude that the biodegradable nanoparticles contained in the suspensions did not affect the aerosol droplet size in a clinically relevant manner; however, both the nanoparticle characteristics and the technique of aerosol generation influence nanoparticle aggregation occurring during aerosolization.