In Vivo & In Vitro Respiratory Models

Start your discovery efficacy and early safety respiratory studies right with lead optimization in vivo and in vitro models. The pharmacology PK/PD and disease models incorporates the aerosol and engineering team, biomarkers, bioanalysis, and histology and special pathology as well as cell and molecular sciences to help you reach efficacy as quickly as possible. 

Core Respiratory In Vivo Models

  • Mechanistic PK/PD models: 
    • Allergic pulmonary inflammation models
    • Non-allergic pulmonary inflammation models
  • Specific airway models
    • Cough model (TRP & anti-tussives)
    • Bronchococonstriction model
  • "Disease" mimicking models:
    • Bleomycin-induced lung fibrosis
    • HDM chronic allergic model
    • Viral, bacterial and fungal pulmonary inflammation/lung injury and infection models 
    • Monocrotaline induced pulmonary artery hypertension
  • Exacerabation model
    • Acute smoke model + Poly (I:C)
Preclinical pharmacodynamic disease models

Respiratory Efficacy Models

Note: Many of our posters are gated to protect proprietary and sensitive content. You'll be asked to create a free login to access the poster.

Animal model  物种 Clinically Relevant Positive Control and MOA of Test Compounds Tested Disease Target Therapeutic Indication Publication
Ovalbumin sensitisation and challenge model  (airway challenge)  Brown Norway Rat, mouse, guinea pig Steroids (systemic and inhaled), dexamethasone, budesonide, fluticasone propionate, PI3Kinase Multiple anti-inflammatory targets 哮喘 Alterations in airway mechanics, inflammatory biomarkers and lung histopathology in a rat model of allergen –induced airway inflammation 
Ovalbumin sensitisation and challenge model  (nasal upper airway challenge)  小鼠 Steroid ( dexamethasone) Multiple anti-inflammatory targets Rhinitis  
House dust mite chronic model  小鼠 IL-5 antibodies, prednisolone, PDE4 (roflumilast) inhaled steroids (budesonide) Multiple anti-inflammatory targets 哮喘 Assessment of the time course of chronic inflammation in the Murine house dust mite model
IL-13 PK/PD goblet cell hyperplasia model  大老鼠 - IL-13 pathways for mucolytics Cystic fibrosis  
LPS neutrophil chemotaxis PK/PD model ( inhaled and systemic) Rat, mouse, guinea pig  Steroids, PDE4 antagonists, P38 MAP Kinases  Neutrophil chemotaxis COPD, neutrophilic  asthma Acute markers of neutrophilic lung infiltration in the nonhuman primate LPS model
Inhaled LPS + FMLP PK/PD model  大老鼠 AZD9668,Sivelestat (NE inhibitors) Neutrophil elastase 慢性阻塞性肺病  
Acute 5, 12 and 17  day Tobacco smoke model (steroid insensitive) 小鼠 PDE4 (Roflumilast), inhaled PDE4 (GSK256066) Multiple anti-inflammatory 慢性阻塞性肺病 Efficacy of an inhaled PDE4 inhibitor, GSK256066, delivered by a novel dry powder preclinical inhalation delivery system in the acute cigarette smoke induced pulmonary inflammation model
Human neutrophil elastase lung haemorrhage model  大老鼠 AZD9668, Sivelestat (NE inhibitors) Neutrophil elastase COPD, bronchiectasis  
Anti-tussive model  Guinea pig codeine Anti-tussives Chronic Cough/ COPD, lung fibrosis)  
Bronchoconstriction models  Guinea pig Beta agonists (LABA) (e.g. Formoterol), Long acting muscarinic agonists (LAMA) e.g. tiotropium and dual pharmacophores muscarinic antagonists/beta agonist (MABA)  e.g Batefenterol Bronchodilators (LABA, LAMA & MABA) COPD (asthma)  
Bleomycin induced lung fibrosis model  Rat , mouse Pirfenidone, Nintedanib  Multiple targets for lung fibrosis Pulmonary Fibrosis (IPF)

Changes in airway platelet population and morphology in a Murine model of lung fibrosis; Correlation of Nintedanib efficacy on fibrotic lesion deposition and lung function within a rat IPF model;

Nintedanib attenuates lung function decline in a Bleomycin-induced rat model of pulmonary fibrosis;

Repeat low doses of Bleomycin induces progressive changes in Murine lung mechanics associated with the development of pulmonary fibrosis;

Chlorine induced lung injury  大老鼠 N/A ( Orphan drug indication) Chemical lung injury  Chemical exposure   
H1N1 viral pulmonary inflammation model  Mouse/Ferret Anti-infectives (Oseltamivir “Tamiflu”) Anti-infectives or viral induce lung injury  Infectious disease/lung injury/COPD exacerbations  Assessment of viral load and time course of pulmonary inflammation in a Murine model of H1N1 (PR8) influenza virus infection
Pseudomonas aeruginosa lung injury and lung infection model  小鼠 Anti-infectives antibiotics/anti-inflammatory/mucolytics Anti-infectives or bacteria induce lung injury  Infectious disease/Cystic Fibrosis/COPD exacerbations  
Allergic Aspergillus  小鼠 Anti-infectives (anti-fungal) Anti-fungals or allergy induce lung injury  Allergic Aspergillosis  

Looking for more disease models? Check out our oncology models and all other in vivo pharmacology models

Histology & IHC for Respiratory

  • Utilized a variety of stains to observe different aspects of inflammation/fibrosis
  • Semi-quantitative blinded scoring with internal peer review
  • Blinded qualititative Ashcroft scoring with internal peer review
  • Digital imaging and quantification available via a collaborative partner
  • IHC antibody method validation (see special pathology LINK)
  • H&E stain -- generated lung pathology and inflammatory cell infiltrate
  • AbPAS -- neutral and combined mucins
  • Masson's trichrome -- collagen deposition
  • PAS Alcian blue -- stains alginate (produced by P. aeruginosa)
  • Giemsa -- used to visualize Gram-negative bacteria

Visit pathology LINK for more services. 

In Vitro Aerosol Testing

  • Ames Assay - OECD 471
    • Standard OECD battery stains
    • TA104 and YG stains
  • NRU toxicity assay - modified method based on ICCVAM, 2006 protocol and OECD 129 
    • CHO
    • Balb/c 3T3
    • NHBE
    • A549
    • H292
  • IVM assay - coming in 2021
  • 3D组织模型
    • EpiAirway (Mattek), MucilAir (Epithelix), EpiOral (Mattek) [need trademarks here!)
    • Endpoints -- MTT, LDH
    • Supplementary endpoints -- TEER, Cilia Beat Frequency (CBF), goblet cell hyperlasia, markers of apopotosis, cytokine analysis and omics