New dry powder system aims to deliver two treatments to the lungs at once

By John Battiston

Inhaled medicine sounds like it should be the simplest kind of medicine there is. You breathe it in, and it goes where it needs to go.

It usually doesn't. The respiratory system evolved as a filter, engineered to trap foreign particles high in the airway so that mucus can clear them. Even the most modern commercial inhalers deliver only about 20% of a dose to an adult's lungs; scale those airways down to a premature infant, and the figure falls to roughly 1%. Inhaled therapeutics fail in testing often because too little of the drug arrives, not necessarily because it is wrong.

For two decades, Virginia Commonwealth University researchers Michael Hindle, Ph.D., and P. Worth Longest, Ph.D., have been engineering that delivery problem from both ends. Hindle, the Peter R. Byron Distinguished Professor and interim chair of the Department of Pharmaceutics in the School of Pharmacy, focuses on formulation. Longest, the Alice T. and William H. Goodwin Jr. Distinguished Chair in the College of Engineering's Department of Mechanical and Nuclear Engineering, handles the device and transport side.

Named VCU's 2025 Innovators of the Year, the pair is now advancing a patent-pending platform that does something no inhaled product currently does: treat the lung's own damaged machinery and the disease at the same time.

Three ingredients, one particle

The platform combines a therapeutic - whether an anti-inflammatory, an antibiotic, an antiviral or a vaccine antigen - with a phospholipid-based synthetic lung surfactant and a hygroscopic material such as salt or sugar.

In the lung, the lipid layer that lines the alveoli and lets them expand and collapse without sticking shut is called the surfactant layer. When a lung is injured, it is among the first things to fail.

"Damage to the surfactant layer is greatly underappreciated right now, because it just hasn't been treatable before without a highly invasive procedure," Longest said. "You need to treat that damage and restore surfactant function, but you also need to treat the inflammation that comes with it. You can think of it as a co-treatment."

While the lung surfactant replaces the damaged surfactant layer, the hygroscopic material absorbs moisture in the lung and swells, so particles small enough to slip past the throat don't simply get exhaled again.

Surfactant also spreads on contact, carrying the co-delivered drug across the enormous internal surface area of the lungs in a thin film. It can potentially carry a drug to regions that are poorly ventilated and therefore hard to reach otherwise.

Even modern commercial inhalers deliver only about 20% of a dose to an adult's lungs, and roughly 1% to a premature infant's. A $50,000 VCU Commercialization Fund award will help Hindle and Longest test a platform that pairs a therapeutic with synthetic lung surfactant and a moisture-absorbing material to reach deep lung tissue. (Photo credit: Will Rummel)

What the funding unlocks

Hindle and Longest received a $50,000 Commercialization Fund award from VCU TechTransfer and Ventures - part of the Office of the Vice President for Research and Innovation - to generate the preclinical efficacy data the platform needs.

Their team has already produced highly dispersible formulations pairing the surfactant with a corticosteroid, several antibiotics and an antiviral. What it has not yet done is show, in a preclinical model of acute inhalation injury, that the combination outperforms either component alone. Proving that level of effectiveness includes three milestones:

• Formulating the powder with two lead therapeutics.
• Establishing a toxic gas or smoke exposure model.
• Measuring treatment outcomes against surfactant-only controls.

"It's really the missing piece of the puzzle for us," Longest said. "We've developed the devices and largely developed the formulation concepts. We need this proof of concept, which will then unlock future funding."

The team is targeting funding from federal resources such as the Department of Defense's Military Burn Research Program - a strong fit, given that the treatment requires no operating room and no specialist. "Treatments for lung injuries occur in an intensive care unit with intubation and ventilatory support, which cost a lot of money and are potentially very harmful for a patient dealing with a lung injury," Hindle said. In a mass casualty scenario, he added, "minutes save lives."

The bigger target

With an estimated 50,000 to 100,000 U.S. cases annually, acute inhalation injury is a deliberately narrow first indication. The platform's reach is far wider: severe viral and bacterial pneumonias, ventilator-associated pneumonia, pediatric pneumonia in low-resource settings and inhaled vaccines, among many other potential applications.

Longest's eye is on acute respiratory distress syndrome, also known as ARDS, the condition that filled ICUs during COVID-19. "There's really no effective treatment for that breathing condition other than trying to support the patient with oxygen," he said. Better still, he added, would be keeping high-risk patients from progressing to ARDS in the first place.

Beyond proof of concept, many hurdles await on the platform's path to commercialization. Toxicology studies, clinical trial materials, inhaler manufacturing and an eventual commercial partner must all occur successfully before the first human dose. "We're very aware that the road to first-in-man is a long road," Hindle said, "and that's something we're hoping to accelerate."

He and Longest have good reason to trust the process. One of the first grants they ever received, in 2008, came from the VCU Technology Validation Fund, a direct predecessor of the TechTransfer and Ventures Commercialization Fund.

"Mike and Worth have been building this portfolio deliberately for years, one validated step at a time," said Thomasine Isler, innovation and industry engagement manager at TechTransfer and Ventures. "Our job is to make sure the commercialization strategy grows alongside the research, protecting each meaningful innovation and creating a pathway for the right partner to ultimately bring these technologies to patients."

Commercialization, Hindle notes, is not the end goal. "We show clinicians images of lungs that look pristine after a lot of damage, because of the therapies we've delivered," he said, referring to preclinical results with the team's earlier surfactant-only formulations. "What excites me most is getting those treatments into their hands and seeing actual responses in patients."