Quenching pharma’s thirst for more targeted aerosol drug delivery systems

As a Minnesota biotech company chases life-saving applications for their research, two VCU professors press forward on their work to use aerosols — tiny particles released into the airways — to deliver advanced drugs to those in need.

Worth Longest, Ph.D.

As a Minnesota biotech company chases life-saving applications for their research, two VCU professors press forward on their work to use aerosols — tiny particles released into the airways — to deliver advanced drugs to those in need.

Michael Hindle, Ph.D., a professor in the VCU Department of Pharmaceutics, and P. Worth Longest, a professor in the VCU Department of Mechanical and Nuclear Engineering, have invested years of time and millions of dollars to address challenges found in the field of medical aerosols.

In particular: While smaller particles are more effective in delivering drugs into the lungs and airways, these tiny particles are often exhaled out immediately when taking a dose.

Current aerosol delivery systems — think asthma inhalers — effectively deliver just 10 percent of an aerosolized dose. That’s fine for most asthma and COPD sufferers who use standard inhalers with existing medications, as these patients only need a small amount of the potent drugs to reach the lungs and have an effect.

“But the medical world wants to use the lungs for delivery of other drugs, whether it's locally to the airways or systemically to the body, and for that, you need more efficient devices,” Hindle says. To effectively use inhaled drugs for complex medical conditions requires more of the aerosol to reach the airways and to potentially target different regions of the airways — plus the devices to get them there.

“Our work is about doing something different — changing that ballgame from having 90% of the drug wasted and 10% make it to the lungs, and flip it so that we get just 10% lost and 90% in the lungs,” Hindle says. “That’s always been our goal.”

Taking aerosols from lab to lung

Over more than a decade, the duo and their teams have created the three keys to making aerosol drug-delivery work: “developing the strategy, developing the device, and developing the formulation,” says Longest, the College of Engineering’s Louis S. and Ruth S. Harris Exceptional Scholar Professor. “When you see inhalation of aerosols fail, or a new pharmaceutical aerosol product fail, one of these areas has often been neglected. Between my lab and the Hindle lab, we have expertise in each of these different areas.”

The fourth component — commercializing their inventions — is underway through a partner in Quench Medical in a deal signed in 2020 thanks to VCU Innovation Gateway. The Minnesota-based company, led by founder and CEO Bryce Beverlin II, Ph.D., has identified lung cancer, severe asthma, and cystic fibrosis as potential initial applications using VCU’s intellectual property, the licensing of which covers both the aerosols and the delivery devices.

“It’s very difficult for an academic institution to develop a drug product,” says Hindle, the Peter R. Byron Distinguished Professor in Pharmaceutics. “So Bryce has moved forward with a team of manufacturers, clinical testing plans, and is talking to the Food and Drug Administration.”

The VCU researchers had not previously pursued lung cancer as a possible application until Quench came along, Hindle says. “The idea that you could deliver a chemotherapy locally to the lungs is obviously very advantageous, because you don't get the systemic side effects through the body like with traditional chemotherapy,” he says. “You're just delivering drugs direct to that site of action for targeting the metastases in the lung.”

In May, Quench presented data using the VCU technology to the Respiratory Drug Delivery conference in Florida showing that using a chemotherapeutic dry powder aerosol in rats was highly effective. It significantly reduced tumor burden but used half of the standard IV-delivered chemo dose. “This approach also aims to decrease the total drug delivered with reduced systemic drug levels in the circulation to decrease systemic toxicity,” the report read. It noted the efforts “solve a critical unmet medical need to develop new strategies to improve treatment outcomes in patients with lung cancer.”

Heavy interest nationally

Hindle and Longest have millions of dollars in funded projects underway, backed by the National Institutes of Health, U.S. Food & Drug Administration, and the Bill & Melinda Gates Foundation.

Their work is building on the reputation of VCU’s Aerosol Research Group, founded in 1988 by emeritus professor Dr. Peter Byron (the name on Hindle’s professorship). The group’s work spans a wide variety of research areas in aerosol formulation and delivery. Hindle and Longest have worked together since 2006.

While Hindle is focused on drug formulations, Longest is the engineering and computer modeling expert. His background is in biological fluid flow, and prior to joining VCU in 2004 had worked in the area of blood flow in vascular disease. But he wanted to differentiate his work, and found VCU’s reputation in medical aerosols was the place he could, in his words, “make an impact.”

Through computer models, Longest and his team can understand how powders or liquids will turn into aerosol particles and the behaviors they will undertake when delivered into the body. “The lung is an area of the body where we have all these complex phenomena occurring with airflow and moving walls,’” he says. “It really takes high performance computers to understand it.”

Drs. Longest and Hindle have developed a series of technology platforms that produce particles that are tiny when entering the lungs to minimize deposition losses in the mouth and throat — but grow in size as they travel down the warm, humid airways. One of the devices uses a mixer-heater to produce tiny particles, other technologies use a pharmaceutical powder or liquid containing a simple hygroscopic excipient such as sodium chloride; it is this excipient that attracts water from the lungs and makes the particles grow and deposit in the lungs with high efficiency.

Eyes on infants

Lately, the pair have been working on a method of aerosol drug delivery to newborns and prematurely born babies. “It’s a different set of challenges when you're trying to deliver aerosols to infants who are born prematurely, and don't have the ability to breathe on their own due to the lack of airway surfactant,” Hindle says. “And that's something that, academically, we thought we were in a position to try and make a contribution to the field.” The group is working with funding from the NIH and the Bill and Melinda Gates Foundation to develop a method of delivering an aerosol surfactant to infants that will hopefully remove the need to intubate these fragile babies.

In addition to striking licensing deals with Quench and building relationships with additional partners, Innovation Gateway has backed the pair’s work with an initial $25,000 from VCU’s Commercialization Fund as well as a just-awarded additional $35,000. “We turned that into a series of intellectual property that has resulted in three licensed patents and a whole family of IP in relation to both formulations and devices,” Hindle says. “There’s been lots of interest in delivering drugs to the lungs, it's just been very difficult to institute any sea change, because the pharmaceutical industry is relatively risk averse.”

And so their research continues, as Quench moves forward to bring their inventions to the bedside.

“What I'm doing, I don't really consider it work — it's an opportunity to interact with great colleagues and contribute to a mission that will be very helpful to a broad range of people,” Longest says. “I also see it as a big responsibility. We want to do this in the right way. Because people's health and lives are at stake. We want to make sure we approach this with a large sense of responsibility, and do our best.”