title: Large porous particles for sustained protection from carbachol-induced bronchoconstriction in guinea pigs.
abstract: OBJECTIVE
  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 FDA-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.
authors.affiliation: Department of Chemical Engineering, The Pennsylvania State University, University Park 16802, USA. axb23@psu.edu
authors.forename: A
authors.initials: A
authors.lastname: Ben-Jebria
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: M L
authors.initials: ML
authors.lastname: Eskew
authors.forename: R
authors.initials: R
authors.lastname: Vanbever
authors.forename: R
authors.initials: R
authors.lastname: Langer
authors.forename: D A
authors.initials: DA
authors.lastname: Edwards
mesh_terms: D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry*; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry*; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D002217:Carbachol / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D006168:Guinea Pigs; D006334:Heart Function Tests / Q000187:drug effects; D008168:Lung / Q000187:drug effects; D008297:Male; D010316:Particle Size; D012119:Respiration / Q000187:drug effects; D013499:Surface Properties
chemical_list: D000318:Adrenergic beta-Agonists; D000336:Aerosols; D003692:Delayed-Action Preparations; D002217:Carbachol; D000420:Albuterol