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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)
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 | Espèces | 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 | Asthme | 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) | Souris | Steroid ( dexamethasone) | Multiple anti-inflammatory targets | Rhinitis | |
| House dust mite chronic model | Souris | IL-5 antibodies, prednisolone, PDE4 (roflumilast) inhaled steroids (budesonide) | Multiple anti-inflammatory targets | Asthme | Assessment of the time course of chronic inflammation in the Murine house dust mite model |
| IL-13 PK/PD goblet cell hyperplasia model | Rats | - | 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 | Rats | AZD9668,Sivelestat (NE inhibitors) | Neutrophil elastase | MPOC | |
| Acute 5, 12 and 17 day Tobacco smoke model (steroid insensitive) | Souris | PDE4 (Roflumilast), inhaled PDE4 (GSK256066) | Multiple anti-inflammatory | MPOC | 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 | Rats | 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) |
Nintedanib attenuates lung function decline in a Bleomycin-induced rat model of pulmonary fibrosis; |
| Chlorine induced lung injury | Rats | 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 | Souris | Anti-infectives antibiotics/anti-inflammatory/mucolytics | Anti-infectives or bacteria induce lung injury | Infectious disease/Cystic Fibrosis/COPD exacerbations | |
| Allergic Aspergillus | Souris | 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
- Modèles de tissus en 3D
- 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
