Article Archive
January/February 2022

Medication Monitor: Medication Delivery Directly to the Lungs
By Lindsey Getz
Today’s Geriatric Medicine
Vol. 15 No. 1 P. 26

Findings from Rutgers University researchers provide an exciting outlook.

With several challenges arising concerning the distribution of the COVID-19 vaccination, evidence of a safe and effective method for delivering medicine directly to the lungs is a particularly exciting development. In December 2020, researchers at Rutgers Cancer Institute of New Jersey and Rutgers New Jersey Medical School announced that they had identified such a method.

Future clinical applications include new therapeutic possibilities as well as a delivery method for vaccinations. Using a pulmonary delivery system, the medication would be transported through the lungs via a physiologic pathway.

“The conceptual idea,” says Renata Pasqualini, PhD, co-corresponding author of the study, “is the possibility of a system of vaccination that people could breathe in with an inhaler. This could completely change our vaccination strategy.”

Understanding the Findings
The research hinged on a molecular discovery that certain particle compounds have the ability to transport from the lungs to the circulatory system. A key finding was the identification of a small protein sequence (peptide), present on the surface of small, benign virus particles (phages) in order to interact with the lung cells. Upon binding, these molecules are transported from the lung tissue into circulation and induce an immune response.

According to Pasqualini, a resident member of Rutgers Cancer Institute and chief of the division of cancer biology, department of radiation oncology at Rutgers New Jersey Medical School, the discovery of a molecular compound that could transport from the lungs into the bloodstream was critical, as this is where the immune response of building antibodies occurs. Pasqualini says the research shows that phage-based vaccines trigger a sustained immune response without indication of any toxic side effects.

In fact, phage particles have already been used safely in clinics for nearly 100 years as a method of treating patients with antibiotic-resistant bacterial infections. Therefore, they have been proven safe in humans.

Because phage particles are highly stable and do not need to be kept frozen, there are enormous implications for what this finding could mean for the future of vaccination access and distribution. The potential of distributing vaccines through the mail could be a true game changer, says Wadih Arap, MD, PhD, director at Rutgers Cancer Institute of New Jersey at University Hospital, chief of hematology-oncology at Rutgers Medical School, and the senior coauthor of the study.

According to the Rutgers Cancer Institute of New Jersey press release announcing these findings, phage particles could be genetically engineered to develop different types of vaccines against other infectious pathogens or medication for a range of targeted aerosol applications. This points to many exciting possibilities for the future.

Given the challenges that have and continue to emerge with the COVID-19 pandemic, a future where vaccines can be mailed could add speed and address challenges related to global access and distribution during the present and future pandemics. This includes the possibility of more quickly and safely reaching members of the older adult population, many of whom have been sheltering in place.

“Considering the fact that the SARS-CoV-2 virus is highly contagious and presents a risk to anyone, isolation/social distancing is the most effective strategy to avoid exposure,” Pasqualini says. “Being able to deliver a vaccination in a friendlier way while keeping individuals in a protected environment could really make a difference in what a future outbreak would look like.”

It also means reaching more of the underserved populations that might not have easy access to hospitals or medical care in the first place. There has been a considerable amount of reporting assessing whether the COVID-19 vaccine has been reaching underserved populations—and in many communities there have been marked disparities.

“There are many populations, including the geriatric population, who have had limitations to gaining access to the COVID-19 vaccine,” Pasqualini explains. “And getting vaccinations out to third-world countries also poses its own set of challenges. The truth is, with this pandemic, we have been faced with an infrastructure problem that we never could have imagined, and it has been a logistical nightmare on many accounts. But these findings mean a new level of preparedness could be adopted at a global level, to address large-scale manufacturing and distribution. While we still have an enormous amount of validation to do before this is ever a reality, the concept that this might even be possible is exciting.”

Beyond distribution, there are also potential advantages to a targeted pulmonary delivery system (over traditional vaccination). This is particularly true for respiratory infections, since the treatment arrives directly to the site of infection.

“This system has been demonstrated to be safe at the doses studied in representative models,” Pasqualini says. “Normally, when you inhale something and it comes into contact with the lungs, you run the risk of it killing or damaging those lung cells. But the compounds used in this delivery system are transported from the lungs to the circulation without damaging lung cells in any way. In our study, no pulmonary damage was observed.”

 “Targeted pulmonary delivery is needle-free and minimally invasive, an attribute particularly relevant in the administration of multidose vaccines or other molecules,” according to Arap, quoted in the Rutgers’ press release. “Also, because the lungs are constantly being exposed to pathogens from the air, they have a high level of immune defense activity and therefore may represent an efficient site for complete immune protection against airborne pathogens.”

Looking Ahead
In addition to using this delivery system for vaccinations, Pasqualini says it also can be used for therapeutics, such as giving insulin to diabetes patients. Insulin could be coupled with the small peptide and undergo transport to ensure it makes it into circulation.

Pasqualini admits more research needs to be done, but the findings so far have been remarkably promising. “What comes next is proving that we can generate an immune response that would be neutralizing against a highly contagious agents such as SARS-CoV-2 or a [tuberculosis] virus—or any other,” she explains. “So, we will be using molecular fragments of the coronavirus and then observing what the immune system does. This will first be performed in animal models until we can ultimately move into clinical trials—so there is a long way to go. But we do have some speed on the table because of the cancer program we are also working on. We have been researching similar entities but with an oncology application, so we already have some of this work underway.”

Numerous challenges have arisen in ensuring the vaccine is distributed widely and swiftly. Arap says that the future applications of these findings could play a role in avoiding the logistical headaches that have arisen during the COVID-19 pandemic. Pasqualini agrees. “The biggest headache that we have is getting vaccinations into large populations at an efficient speed—and it’s been made clear in many ways that we just weren’t ready,” she says. “But the advantage to these findings would be the ability to manufacture and distribute vaccinations in a large-scale way that is safe and doesn’t require refrigeration. It could really change the future of vaccination.”

— Lindsey Getz is an award-winning freelance writer in Royersford, Pennsylvania.