By Dan Carrigan

After multiple prototypes and more than a decade of collaboration, two Virginia Commonwealth University inventors are closer than ever to bringing a potentially lifesaving device to premature infants around the world.

The innovation – a handheld dry powder inhaler for newborns in respiratory distress – recently cleared a proof-of-concept milestone, with results published in a peer-reviewed journal. Now, inventors Michael Hindle and Worth Longest are focused on proceeding quickly toward clinical trials.

“Hopefully within one to two years, we could get this into babies and actually save some lives,” said Hindle, Ph.D., the Peter R. Byron Distinguished Professor in the VCU School of Pharmacy’s Department of Pharmaceutics. “We’re trying to deliver something that babies need to be able to breathe.”

Premature infants born with underdeveloped lungs lack surfactant, a naturally occurring substance that reduces surface tension and keeps airways open. In many parts of the world, particularly low- and middle-income countries, invasive delivery methods like intubation are not feasible, and the availability of physicians and ventilators is limited.

“So the idea that you could walk up to an infant in a fairly nontechnical setting and noninvasively give that surfactant is really going to be lifesaving for millions of babies who don’t have access to treatment right now,” Hindle said.

A story of time and talent

The project’s origins go back 15 years, with its development bridging VCU’s Monroe Park and MCV campuses. And while the solution may look simple, the engineering behind it is anything but.

“We probably made maybe too many prototypes – [more] than we should have,” joked Longest, Ph.D., the Alice T. and William H. Goodwin Jr. Endowed Professor in the VCU College of Engineering’s Department of Mechanical and Nuclear Engineering. “But because we have the 3D-printing technology, we can come up with an idea, turn it around and test it the next day. Over the years, it’s been hard to put a number on it, but we’re probably in the thousands.”

Their commitment has resulted in a low-cost, compact device that uses four simple squeezes to create a high-efficiency aerosol capable of reaching deep into a newborn’s lungs – and without the need for electricity, intubation or a ventilator. That would allow health care providers to deliver lifesaving therapy quickly and noninvasively to premature babies.

Today, those treatments often begin with intubation – an urgent, difficult and high-stress procedure for providers and families – as well as the use of liquid surfactant.

“With our approach, we see really rapid response at doses that are unheard of for surfactants, because we’re able to deliver such very small particles as an aerosol cloud right to that site of action, deep in their lungs, that other people have not been able to do before,” Hindle said.

Taking a major step forward

Earlier this year, Hindle and Longest completed their first proof-of-concept study, with strong results for delivering aerosolized surfactant through a nose and into the lungs in preclinical models. In April, the team published its findings in the Journal of Aerosol Medicine and Pulmonary Drug Delivery, showing that its hand-actuated dry powder inhaler and surfactant formulation outperformed the current clinical standard in preclinical model testing.

“It’s basically the complexity of a rocket engine without combustion,” Longest said of the inhaler. “And we’ve embedded that into a device simple enough to squeeze by hand.”

The targeted delivery of the surfactant therapy to the alveolar regions of the lungs –  the tiny air sacs where oxygen enters the bloodstream – produced five to 12 times faster oxygenation recovery and provided double the improvement in lung compliance compared with the standard liquid method. Notably, these improvements were achieved with only one-tenth of the liquid dose and were delivered in less than five minutes.

“The next steps now are to think about commercialization,” Hindle said. “We have to take what we’re doing in the lab, where we’ve manufactured the powders and the devices on relatively small scales, and actually think about manufacturing at much larger scales.”

That means galvanizing the teams to prepare for toxicology studies, formulation stability testing and the regulatory steps needed to bring the device out of the lab and into clinical use. The project has been supported by the National Institutes of Health, the Food and Drug Administration, the Bill and Melinda Gates Foundation and the pharmaceutical industry.

Finding support for the journey

At VCU, Hindle and Longest have had ongoing support from TechTransfer and Ventures, which helps commercialize campus innovations through intellectual property protection, commercialization planning and licensing strategy.

“This is the kind of project that shows what’s possible when long-term research collaboration meets patient-centered design,” said Thomasine Isler, innovation and industry engagement manager at TechTransfer and Ventures. “Our role has been to protect the team’s ideas and connect them with the right resources to move toward commercialization. It’s rewarding to see it this far along.”

The support has already led to licensing deals. Some of the team’s related particle and device technologies have been licensed for applications in chemotherapy, and more partnerships are in discussion. The team already is working on scaling the platform for broader applications, including drug delivery for adults with COVID-19, sepsis and acute lung injury.

“We’ve really sought out unmet needs, clinical challenges where this high-efficiency delivery is really needed,” Hindle said. “And we’ve kept the technology simple enough to move forward quickly.”

With commercialization efforts in motion and support from key partners, both inventors say the ultimate reward is knowing what the device could mean for patients.

“If we can commercialize that technology, we can improve the delivery of surfactant and a number of other medications as well,” Longest said. “I find it very rewarding, largely because of the need that exists.”