title: Aerosolized montelukast polymeric particles-an alternative to oral montelukast-alleviate symptoms of asthma in a rodent model.
abstract: OBJECTIVE
  Cysteinyl leukotrienes (CysLTs) propagate inflammatory reactions that result from allergen exposure in asthma. Montelukast, a CysLT type-1 receptor antagonist, disrupts mediator-receptor interactions and minimizes inflammatory response. In this study, we have evaluated anti-asthmatic efficacy of inhalable montelukast-loaded large porous particulate formulations in ovalbumin-induced rat airway inflammation model that mimics asthma.
  
  
  METHODS
  The anti-inflammatory effects of a montelukast-loaded formulation were investigated in rats by measuring the total protein content, levels of injury markers and number of inflammatory cells in the bronchoalveolar lavage fluid (BALF). The histopathological studies assessed the morphological and structural changes that occur in asthmatic lungs. Animals were also challenged with methacholine to examine the airway hyper-reactivity.
  
  
  RESULTS
  Compared with healthy animals, asthmatic animals showed a 3.8- and 4.77-fold increase in the protein content and number of inflammatory cells in BALF, respectively. Intratracheal montelukast particles reduced the protein content by 3.3-fold and the number of inflammatory cells by 2.62-fold. Also, montelukast particles reduced the lactate dehydrogenase (LDH) and myeloperoxidase (MPO) levels by a 4.87- and 6.8-fold in BALF, respectively. Montelukast particles reduced the airway wall thickness by 2.5-fold compared with untreated asthmatic lungs. Further, particulate formulation protected the lungs against methacholine-induced bronchial provocation (p < 0.05).
  
  
  CONCLUSIONS
  Respirable large porous particles containing montelukast alleviated allergen-induced inflammatory response in an animal model and prevented histological changes associated with asthma. Thus montelukast-loaded large porous polylactic acid (PLA) particles could be an aerosolized delivery approach for administration of currently available oral montelukast.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter Drive, Amarillo, Texas, 79106, USA.
authors.forename: Brijeshkumar
authors.initials: B
authors.lastname: Patel
authors.forename: Nilesh
authors.initials: N
authors.lastname: Gupta
authors.forename: Fakhrul
authors.initials: F
authors.lastname: Ahsan
mesh_terms: D000085:Acetates / Q000008:administration & dosage*; D000336:Aerosols / Q000008:administration & dosage*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D003521:Cyclopropanes; D003545:Cysteine / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000008:administration & dosage; D015289:Leukotrienes / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage; D009195:Peroxidase / Q000378:metabolism; D011091:Polyesters; D011108:Polymers / Q000008:administration & dosage*; D011804:Quinolines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides
chemical_list: D000085:Acetates; D000336:Aerosols; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D003521:Cyclopropanes; D015289:Leukotrienes; D011091:Polyesters; D011108:Polymers; D011804:Quinolines; D013440:Sulfides; C112381:cysteinyl-leukotriene; D019344:Lactic Acid; C033616:poly(lactide); D010047:Ovalbumin; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D003545:Cysteine; C093875:montelukast