Regional lung deposition of nebulized liposome-encapsulated ciprofloxacin

Abstract

Liposome-encapsulated ciprofloxacin (22.2 mg ciprofloxacin/ml) was nebulized in 25 nebulizers (five nebulizers from each of five nebulizer types). The aerosol was inhaled by a breath simulator (square wave pattern, 0.75 l tidal volume, 0.3 l/s inhalation flow rate) and inhaled droplet sizes were characterized using in-line phase Doppler anemometry. Filter collection combined with centrifugation, UV spectrophotometry and measurement of original entrapment efficiency using C 14-radiolabelled ciprofloxacin was used to determine % encapsulation in the inhaled aerosol. Cascade impaction combined with chemical assay showed that encapsulated and free ciprofloxacin were homogeneously distributed among the inhaled droplet sizes. Combination of the above measurements with a mathematical lung deposition model allowed prediction of the amounts of encapsulated ciprofloxacin depositing in the tracheo-bronchial, alveolar and extrathoracic regions of the respiratory tract. The nebulizer types (Pari LC STAR, Pari LC+, Medix Sonix 2000, Hudson T-Updraft II, DeVilbiss Permaneb) differed by up to a factor of 30 in the amount of encapsulated ciprofloxacin depositing in the different regions of the lung (e.g. lung deposition of entrapped ciprofloxacin varied from 0.7% to 18.1% of total ciprofloxacin dose placed in the nebulizer). Much of this dramatic difference was due to the differing amounts of liposomal disruption, which varied among the different nebulizer types from no measurable disruption to nearly complete disruption.