Following the concentration of polymeric nanoparticles during nebulization.
OBJECTIVE
Nebulization represents one strategy to achieve pulmonary deposition of biodegradable nanoparticles. Besides stability as a key requirement to maintain functionality, the output of nanoparticles from the nebulizer needs to be considered to facilitate an efficient pulmonary therapy.


METHODS
Formulations nebulized by air-jet and vibrating-membrane technology were analyzed for their aerodynamic characteristics by laser diffraction. The nebulization stability of poly(D,L-lactide-co-glycolide) nanoparticles was assessed by dynamic light scattering. Moreover, several methods were employed to account for the shift in solute and NP reservoir concentration during nebulization.


RESULTS
Regardless of the formulation or nebulizer used generated aerosols all showed aerodynamic characteristics suitable for deep lung deposition. However, nanoparticles were prone to aggregation and concentrated during air-jet nebulization. The particle concentration effect was significantly pronounced in comparison to molecular solutes under the same nebulization conditions, due to nanoparticle aggregation and subsequent particle remainder in the reservoir. In contrast, vibrating-membrane technology did not affect nanoparticle integrity and reservoir concentration during nebulization, as the unaffected submicron particles passed through the tapered holes of the actuated plate.


CONCLUSIONS
Aggregation and concentration effects during air-jet nebulization emphasize that nanosuspensions should preferably be delivered with a suitable vibrating-membrane device in order to ensure an effective pulmonary application.
Medical Clinic II, Department of Internal Medicine, Justus-Liebig-Universität Giessen, Klinikstrasse 33, 35392 Giessen, Germany. moritz.beck-broichsitter@innere.med.uni-giessen.de
Moritz
M
Beck-Broichsitter
Marie-Christine
MC
Knuedeler
Thomas
T
Schmehl
Werner
W
Seeger
D000336:Aerosols / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000648:ultrastructure; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D000336:Aerosols; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid