The process of identifying and bringing to market novel therapies is extremely challenging and notoriously expensive as most drug candidates fail. In the respiratory area, like in other areas, improving the success rate of new therapeutic entities is one of the industry’s greatest challenges. To do so, the use of reliable methodologies providing sensitive, reproducible, and detailed outcomes predictive of clinical success is key in guiding the strategic decision-making process.
TRUSTED OUTCOMES, INDUSTRY STANDARD
The flexiVent has proven to be an invaluable tool in early drug development. Over the years, it has become the industry standard in terms of preclinical lung function measurements, as evidenced by an ever growing number of related scientific publications and patents. The flexiVent’s exhaustive set of highly reproducible measurements offers outcomes that can be trusted at any point during the preclinical drug development process. The detailed measurements help gather deep insights into respiratory mechanisms early on in the process, preventing additional development costs.
- SCIREQ Application Note: The flexiVent in the Asthma Drug Development Process
- List of drug-related patents citing the flexiVent
- Benchmarking of Human Dose Prediction for Inhaled Medicines from Preclinical In Vivo Data – Ericsson, T. et al. Pharmaceutical Research, 34(12), pp. 2557–2567. 2017.
- The Antibacterial and Anti-inflammatory Activity of Chicken Cathelicidin-2 combined with Exogenous Surfactant for the Treatment of Cystic Fibrosis-Associated Pathogens – Banaschewski, B. J. H. et al. Scientific Reports volume 7, Article number: 15545. 2017.
- Pulmonary administration of phosphoinositide 3-kinase inhibitor is a curative treatment for chronic obstructive pulmonary disease by alveolar regeneration – Horiguchi, M. et al. Journal of Controlled Release. 213, pp. 112–119. 2015.
- A purinergic P2Y6 receptor agonist prodrug modulates airway inflammation, remodeling, and hyperreactivity in a mouse model of asthma – Chetty, A. et al. Journal of asthma and allergy. 11, pp. 159–171. 2018.
- Bilirubin nanoparticles ameliorate allergic lung inflammation in a mouse model of asthma – Kim, D. E., et al. Biomaterials, 140, 37–44. 2017.
REPRODUCIBLE INTERVENTION, PREDICTIVE OUTCOMES
The administration of drugs or novel therapeutic carriers through the lung could be desirable for many reasons. The large surface area and high vascularization of the lung can provide a fast and effective delivery of substances either locally or systemically, via the blood. When considering inhalation as the route for drug delivery, SCIREQ’s intervention platform, the inExpose, offers a significant positive impact on study reproducibility and research efficiency by ensuring process standardization. Integrated with the Aeroneb nebulizer, the inExpose provides sophisticated computer control which enables automated, precise, and repeatable aerosol exposure sessions to small laboratory animals. Furthermore, the inExpose offers small internal volumes, reducing exposure ramp-up times and minimizing the need for large quantities of material.
CONCIOUS MEASUREMENTS, SPONTANEOUS BREATHING
Respiratory function can be assessed by a number of techniques. Measurements in conscious subjects can be done using various plethysmography techniques such as unrestrained whole body plethysmography (WBP), double chamber plethysmography (DCP), or head-out plethysmography (HOP). While these measurement methods offer the benefit of having the subjects closer to their natural state, uninfluenced by anaesthetic side effects, the trade-off is a lower measurement accuracy and precision.
A comprehensive overview of the pharmacological properties of novel therapies is required to best identify the candidates to move forward in the drug development process. This can be achieved through a range of techniques which includes the classical isolated tissue bath, where external influences can be removed.
- Airway smooth muscle in the pathophysiology and treatment of asthma – Doeing et al. J Appl Physiol 114:834-843, 2013
- Measurement of smooth muscle function in the isolated tissue bath – applications to pharmacology research – Jespersen et al. J Vis Exp 95: e52324, 2015
- Increased contractility of isolated lung parenchyma in an animal model of pulmonary fibrosis – Evan et al. Am Rev Respir Dis 125: 89-94, 1982
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