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Applicability of an Ultrasonic Nebulization System for the Airways Delivery of Beclomethasone Dipropionate in a Murine Model of Asthma
Authors:Boška Hrvačić  Berislav Bošnjak  Marijan Tudja  Milan Mesić  Mladen Merćep
Affiliation:(1) PLIVA Research Institute Ltd., Prilaz baruna Filipovića 29, HR-10000 Zagreb, Croatia;(2) PLIVA Croatia Ltd., Zagreb, Croatia
Abstract:Purpose We have assessed the use of an ultrasonic nebulization system (UNS), composed of ultrasonic nebulizer and diffusion dryer filled with charcoal, for the effective delivery of beclomethasone to the airways in a murine asthma model.Methods Solution of beclomethasone in ethanol was aerosolized using an ultrasonic nebulizer. Passage of the aerosol through a drying column containing charcoal and deionizer produced dry beclomethasone particles. Particles were delivered to BALB/c mice placed in a whole-body exposition chamber 1 h before intranasal challenge with ovalbumine. Efficacy of beclomethasone delivery was evaluated by examining bronchoalveolar lavage fluid (BALF) cytology.Results Effect of three UNS system parameters on aerosol particle size was investigated. The critical parameter affecting the size of dry particles was beclomethasone concentration in aerosolized solution and solution flow rate while power level of ultrasonic nebulizer generator had no effect. Administration of beclomethasone at calculated dose of 150 μg/kg to mice significantly decreased total cell number and relative eosinophil number in BALF.Conclusions The UNS system produces a monodisperse aerosol that can be used for inhalative delivery of poorly water soluble substances to experimental animals. The UNS system minimizes formulation requirements and allows rapid and relatively simple efficacy and toxicity testing in animals.
Keywords:asthma  beclomethasone dipropionate  dry powder  inhalation delivery  mice  ultrasonic nebulization system
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