PreciseInhale turns 3R challenge into opportunity
Meeting 3R regulations (replacing, refining and reducing the number of animals in research) is an increasingly common requirement for research funding in Europe. PreciseInhale’s two in vitro modules, and its one-animal-at-a-time testing system, allow researchers to replace and reduce the number of animals needed for PK research, whilst still delivering exceptional data. ISAB Chief Science Officer Dr Per Gerde explains.
The 3R era is with us. In Europe, government funding for environmental research is increasingly tied to meeting 3R research requirements. It is a major opportunity for research institutes. Technologies that can meet 3R requirements and deliver high-quality data are much sought after. ISAB’s dry powder inhalation R&D platform PreciseInhale has been embraced by environmental researchers and inhaled drug developers for its in vitro capabilities, range of exposure modules, exceptional data and ability to meet 3R requirements.
Replace and cross-validate
The PreciseInhale platform has two in vitro models that replace animal testing: DissolvIt and the in vitro cell exposure module. Thermostatted at 370C, DissolvIt simulates the dissolution and absorption of soluble particles in the lung epithelium, the air/blood barrier of the conduction airways. The in vitro cell exposure module also delivers exceptional data on the cellular effects of airborne particles. It is a novel exposure system for airlifted cell cultures that uses a dynamic perfusion system, producing results that resemble the physiology of the living lung more accurately than conventional static systems.
As with all PreciseInhale’s eight modules, both produce realistic aerosol exposures from minute amounts of collected / available study material, typically requiring 50 mg or less for a full PK study – a significant advantage for toxicologists, where scarcity of material and the need for respirable aerosol is an acute problem. And both deliver exceptionally accurate, detailed data.
But the in vitro modules don’t just deliver accurate data cost-effectively. In the PreciseInhale system the same aerosol generated from a small amount of test substance can be used to expose a whole chain of exposure modules from airlifted cell cultures to isolated perfused lungs to animals and humans in vivo. This allows cross-validation of both the pharmacokinetic effects of inhalation as well as dynamic endpoints using the same aerosol atmospheres.
Dr Per Gerde: “The in vitro models allow you to cross-validate measured responses, kinetic- as well as dynamic, over relevant exposure models. Cross-over studies can be carried out using the same controlled exposure aerosols throughout the series, directly benchmarking the exposure models on critical biological parameters against each other without introducing discrepancies from divergent exposure methods.”
Reduce the number of animals and the stress on animals
Unlike conventional ‘tower’ testing systems PreciseInhale is built around a unique one-animal-at-a-time testing system which drastically reduces the number of animals needed for inhalation research, and the standard deviation of results. The result is more refined, controllable dosing, which reduces the stress on the individual animal during testing.
Dr. Per Gerde: “With multiple animal exposures in inhalation towers a major problem is that the delivered dose cannot be adjusted to the ventilation pattern and aerosol concentration delivered to each individual animal. This is a major reason why the PreciseInhale system exposes animals one at a time, calculating the cumulated inhaled dose of each animal in real time based on their ventilation pattern and the aerosol concentration in their breathing zone. As a result the standard deviation in the deposited dose is substantially reduced. Because PreciseInhale’s aerosol generator unit separates the powerful energy released during aerosolization from the individual’s rodent’s delicate lungs, PreciseInhale avoids the lower quality data and unwanted lung lesions that can occur in conventional technologies where the test powder is either instilled as a liquid or released in one focused blast.”
PreciseInhale allows human inhalation testing too, built on a firm 3R foundation. “The last important aspect of aligning inhalation exposure methods with 3R is to enable exposures in humans as early as possible under safe conditions,” says Dr Gerde. “This is a necessary step to fully utilizing the potential of the PreciseInhale platform as an important translational tool in respiratory research. There are plans to introduce the platform in two clinical applications; diagnostics and drug development.”
