Large Porous Particles for Sustained Protection from Carbachol-Induced Bronchoconstriction in Guinea Pigs |
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Authors: | Ben-Jebria Abdellaziz Chen Donghao Eskew Mary Lou Vanbever Rita Langer Robert Edwards David A. |
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Affiliation: | (1) Department of Chemical Engineering, The Pennsylvania State University, 133 Fenske Lab., University Park, Pennsylvania, 16802;(2) Environmental Resources Research Institute, The Pennsylvania State University, University Park, Pennsylvania, 16802;(3) Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139;(4) Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France |
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Abstract: | Purpose. To determine whether a new formulated albuterol aerosol could sustain inhibition to bronchoconstriction for approximately one day in guinea pigs challenged with carbachol.Methods. Large and porous particles, comprising a combination of endogenous or PDA-approved excipients and albuterol sulfate, were prepared by spray drying using a NIRO portable spray drier. The anesthetized animals inhaled 5 mg of large porous or small nonporous particles by forced ventilation via cannulae inserted in the lumen of their exposed tracheae. At regular intervals over a period of 36 hours after drug delivery, airway resistance was determined in response to carbachol challenge dose.Results. Whereas inhalation of small nonporous albuterol particles protected from the carbachol-induced bronchoconstriction for up to 5 hours, inhalation of large porous albuterol particles produced a significant inhibition of carbachol-induced bronchoconstriction for at least 16 hours.Conclusions. The absence of substantial side effects, verified over a period of 24 hours by evaluating cardio-respiratory parameters as well as pulmonary inflammation, supports the utility of large porous albuterol particles for sustained therapies in asthma and other types of lung disease.Dr. Ben-Jebria is also affiliated with |
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Keywords: | large and light particles albuterol inhalation prolonged bronchodilation guinea pigs |
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