Acute respiratory distress syndrome (ARDS) is an inflammatory lung condition that has become the leading cause of death in COVID-19 patients. This rapidly progressing disease is characterised, among other factors, by the depletion of the lungs’ inner liquid coating, necessary for the lung’s expansion. This is exacerbated by the coronavirus. “There is at present no effective treatment against this,” notes the EU-supported LIFT project coordinator Josué Sznitman, associate professor of biomedical engineering at Technion – Israel Institute of Technology. “Patients are mechanically ventilated with supplemented oxygen, in the hope that their lungs can heal themselves. However, about 40 % of those afflicted with ARDS are likely to die.”
Better drug delivery
A key challenge in treating this condition is getting the medication to where it is needed within the lungs. Common devices, such as nebulisers, are unable to effectively deliver drugs to the lungs, since only small particles can be inhaled, so doses remain low. Direct instillations of liquids into the lungs lead to bad drug distribution, as liquids drain downwards with gravity. The LIFT project sought to address this by developing a unique foam formulation and delivery device, to treat ARDS and, potentially, other lung conditions. “We wanted to demonstrate, in this project, that delivery of our foamed surfactant, used to replace the lungs’ inner liquid coating, could be an effective treatment,” says Sznitman. “We wanted to show that our foam is superior to liquids which have been unsuccessfully used in previous clinical trials.” Using rat and pig models, the project team set about demonstrating the efficacy of its patent pending technology. A working prototype of the Liquid Foam Therapy (LIFT) drug delivery device was constructed, and preclinical experiments were carried out using rats first. Following successful results in rats, they then used porcine lungs. “Pig lungs were used to see if the treatment and the device would be effective in achieving homogenous drug distribution in larger human-sized lungs,” explains Sznitman.
New lung treatments
The project team was able to demonstrate how foam can be effectively delivered to coat the inner lungs, opening the door to a new era of treatments for ARDS and other lung conditions. The successful animal trials conducted during the LIFT project enabled the team to start preclinical trials in large animals. These will hopefully enable the team to start clinical trials, treating – and ultimately saving the lives of – real patients. “The long-term goal is that this will become the gold standard for treating ARDS,” says Sznitman. The project team is also looking to broaden the use of this technology to deliver other therapies. “For example, we are exploring the possibility of delivering large doses of steroids to treat ARDS, including for severe COVID-19 patients,” notes Sznitman. “The results of the LIFT project have the potential to extend far beyond ARDS treatments,” he remarks. “This drug delivery technology can be leveraged for other lung therapies, such as delivering stem cells directly to the lungs to treat conditions like chronic obstructive pulmonary disease (COPD).” To realise all this potential, a start-up company, called Neshima Medical, has been launched. The aim is to bring these life-saving treatments for lung disorders to market as quickly and as safely as possible. “We plan to finalise the clinical prototype of our delivery device by the end of 2020, and then prepare for clinical trials,” adds Sznitman. “We are confident that we will be bringing to market a breakthrough pulmonary drug delivery device, applicable across a broad range of lung diseases.”
LIFT, ARDS, COVID-19, coronavirus, lungs, surfactant, pulmonary, drug, diseases