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

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Animal model	Species	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	Asthma	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)	Mouse	Steroid ( dexamethasone)	Multiple anti-inflammatory targets	Rhinitis
House dust mite chronic model	Mouse	IL-5 antibodies, prednisolone, PDE4 (roflumilast) inhaled steroids (budesonide)	Multiple anti-inflammatory targets	Asthma	Assessment of the time course of chronic inflammation in the Murine house dust mite model
IL-13 PK/PD goblet cell hyperplasia model	Rat	-	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	Rat	AZD9668,Sivelestat (NE inhibitors)	Neutrophil elastase	COPD
Acute 5, 12 and 17 day Tobacco smoke model (steroid insensitive)	Mouse	PDE4 (Roflumilast), inhaled PDE4 (GSK256066)	Multiple anti-inflammatory	COPD	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	Rat	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	Rat	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	Mouse	Anti-infectives antibiotics/anti-inflammatory/mucolytics	Anti-infectives or bacteria induce lung injury	Infectious disease/Cystic Fibrosis/COPD exacerbations
Allergic Aspergillus	Mouse	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.

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 tissue models
- EpiAirway™ (Mattek), MucilAir™ (Epithelix), EpiOral™ (Mattek)
- Endpoints -- MTT, LDH
- Supplementary endpoints -- TEER, Cilia Beat Frequency (CBF), goblet cell hyperlasia, markers of apopotosis, cytokine analysis and omics

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

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In Vivo & In Vitro Respiratory Models

Core Respiratory In Vivo Models

Respiratory Efficacy Models

In Vitro Aerosol Testing

Histology & IHC for Respiratory

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