Featured Post from VCU College of Engineering

At VCU, engineering and pharmacy join forces to make inhaled medications more effective for infants and children

Oct 31, 2019

3 min

Pharmaceutical aerosols are painless, fast-acting and less likely to cause side effects than medicines delivered via pills or injections. Yet inhaled therapies are often avoided because of the challenges associated with targeting how aerosol particles are deposited within the lung.


“Current inhalers produce fairly large particles, so approximately 90 percent of the medication gets lost in the mouth and throat. It’s swallowed and wasted. This prevents many medications from being delivered through the inhalation route, even though there are a number of advantages to be gained, such as improved efficacy and reduced side effects,” said Worth Longest, Ph.D., the Louis S. and Ruth S. Harris Exceptional Scholar Professor in the Department of Mechanical and Nuclear Engineering in the VCU College of Engineering.


Simply making the particles smaller isn’t a solution.


“The problem with making the particles smaller is that they go in really well — but they also come straight back out during exhalation,” said Michael Hindle, Ph.D., the Peter R. Byron Distinguished Professor in the VCU School of Pharmacy.

With three National Institutes of Health R01 grants totaling more than $7 million, Longest and Hindle are applying a combined engineering and pharmaceutical approach to make inhaled medications more effective and available.


In “High-Efficiency Aerosol Delivery Using the Excipient Enhanced Growth Concept: A Human Proof of Concept Study,” Longest and Hindle have created a novel platform that produces particles that are tiny when they enter the lungs — but grow in size as they travel down the warm, humid airways. This platform comprises a device that uses a mixer-heater to produce tiny particles, about one-fifth the size of those from conventional inhalers.


With this delivery concept, a pharmaceutical powder or liquid is enhanced with a hygroscopic excipient, essentially a substance that attracts water. “Your lungs are full of water,” Hindle said. “So if you put something inside your lungs that likes water, it’s going to swell and grow in size and not be expelled.” Using sodium chloride — salt — as the hygroscopic excipient, they have tested their system in vitro.

The results have been promising.


“We’ve flipped the needle,” Longest said. “Previously, only 10 percent of the initial dose would reach the lung, and that 10 percent was poorly targeted within different lung regions. With our approach, you can get 90 percent in and distribute that 90 percent evenly, or target a specific lung region.”


The researchers will begin testing their method on adults in two human proof-of-concept trials beginning in late 2019 and early 2020.


In two separate, but related, NIH studies, Longest and Hindle are adapting this concept for patients ranging in age from newborn to six. Each project proposes a device approximately the size of a lipstick tube that contains a pediatric formulation (liquid or powder) enhanced with a hygroscopic excipient. There are currently no inhalers on the market specifically designed for children or infants, even though their inhaling patterns and volumes differ from those of adults. Pediatric patients therefore must use adult-sized devices.


One study focuses on targeted lung delivery of the antibiotic tobramycin to children with cystic fibrosis, a population prone to respiratory infection because of overproduction of mucus in the lungs. Pediatric cystic fibrosis patients with lung infections usually receive the medication via, 20-minute nebulizer treatments daily, sometimes up to four per day.


Longest and Hindle’s proposed alternative is a pediatric dry powder inhaler that is fast and easy to use. Because its particles are engineered to reach the deep lung, it is expected to eradicate infection more efficiently because there is less risk of resistant strains of bacteria forming in undertreated regions of the lung.


The other study focuses on delivery of surfactant aerosols to premature infants. Surfactant is a substance found in healthy lungs that keeps the tissue supple enough to expand and contract properly. The respiratory system is among the last to develop in utero, so in newborns and preemies, this substance is sometimes not fully developed — or not present at all.


When these infants experience severe respiratory distress, the current protocol is to intubate and administer large doses of liquid surfactant to the lung by way of the throat. This highly invasive and potentially dangerous procedure causes distress and blood pressure fluctuations. In this third NIH-funded study, the researchers are also developing a tiny, small volume nebulizer and a dry powder inhaler for efficient, noninvasive respiratory support for infants.





Powered by

You might also like...

Check out some other posts from VCU College of Engineering

2 min

Department of Energy awards $928,000 to Lane Carasik, Ph.D., for fusion energy systems research

The Department of Energy (DOE) recently announced $128 million of funding for seven Fusion Innovation Research Engine (FIRE) Collaboratives. Virginia Commonwealth University (VCU) College of Engineering researchers will support the project titled “Advancing the maturity of liquid metal (LM) plasma facing materials and first wall concept” led by the Department of Energy’s Princeton Plasma Physics Laboratory (PPPL). This includes $928,000 to support research led by Lane Carasik, Ph.D., assistant professor in the Department of Mechanical and Nuclear Engineering, as part of a multi-institution effort for fusion energy systems. The FIRE Collaborative seeks to advance the maturity of liquid metal plasma-facing materials and wall concepts. High operating temperatures within fusion energy systems pose a significant material design challenge. Research will help solve technical problems with liquid metal plasma-facing materials and first wall concepts, including four main challenges: testing protective materials, understanding material properties, studying how liquid metals behave in magnetic fields and developing new liquid metal alloys. The goal is to make liquid metals viable for fusion pilot plant designs. “The work done by VCU as part of the FIRE Collaborative will help raise the technology readiness of Liquid Metal based fusion energy concepts. Over the next four years, we will train undergraduate and graduate students on how to extract electricity from these fusion concepts,” Carasik said. Rajesh Maingi, Ph.D., is the lead primary investigator at PPPL. Institutional investigators for the group include Sergey Smolentsev, Ph.D., Oak Ridge National Laboratory (ORNL); Vsevolod Soukhanovskii, Ph.D., Lawrence Livermore National Laboratory (LLNL); Daniel Andruczyk, Ph.D., University of Illinois Urbana-Champaign; Bruce Koel, Ph.D., Princeton University; Michael Kotschrenreuther, Ph.D., ExoFusion; Xing Wang, Ph.D., The Pennsylvania State University; Kevin Woller, Ph.D. from Massachusetts Institute of Technology; and Carasik from VCU. Up to $220 million is expected to fund the FIRE Collaboratives over four years, with $31 million allocated for the 2025 fiscal year. Future distributions are dependent on congressional appropriations.

3 min

Mechanical and Nuclear Engineering professor John Speich, Ph.D., advances bladder biomechanics research through collaboration with VCU School of Medicine

The year was 2003, and John Speich, Ph.D., professor in the Department of Mechanical & Nuclear Engineering, felt like he had a clear sense of the direction his burgeoning career was heading in. Speich had recently completed his doctorate in mechanical engineering from Vanderbilt University, where he concentrated on robotics. Following Vanderbilt, Speich went on to become an associate professor at the Virginia Commonwealth University (VCU) College of Engineering, working with students in the Department of Mechanical & Nuclear Engineering. Leveraging his robotics expertise, Speich planned to continue his work developing robotics for medical surgery and rehabilitation. Then Speich got a call from Paul Ratz, Ph.D., a professor at the VCU School of Medicine, asking for assistance that would change the entire focus of Speich’s career. Ratz used a small robotic lever that moved up and down just a few millimeters to stretch tiny strips of bladder muscle and rings of artery, trying to determine how different chemical compounds changed the mechanical properties of the muscle. Speich was intrigued—this was a form of mechanical engineering. “In mechanical engineering, we pull on things to determine the mechanical properties,” says Speich. “Here, Dr. Ratz was pulling on pieces of bladder instead of the typical substances mechanical engineers are known to work with, like steel, aluminum or plastic.” Speich and Ratz began working together in 2003, and now, because of that unique partnership, nearly all of the research Speich does is about the bladder. “Before I started working with Dr. Ratz, I had never even heard the words neurourology or urodynamics,” says Speich. “Now, Neurourology and Urodynamics is the name of the journal I publish in the most.” Today, Speich collaborates on bladder biomechanics with two doctors at VCU Health. Adam Klausner, MD is a urologist and the interim chair of the new Department of Urology at VCU. Linda Burkett, MD is a urogynecologist from the Department of Obstetrics and Gynecology; prior to medical school, Burkett completed her bachelor’s degree in Biomedical Engineering from the VCU College of Engineering. Together, Speich, Klausner and Burkett aim to find non-invasive methods to characterize and diagnose overactive bladder, with the goal of allowing doctors to precisely match patients with the most effective treatments. A number of students across the VCU College of Engineering and VCU School of Medicine have aided in their research, including recent Biomedical Engineering graduate Mariam William. Speich’s primary methods of research involve Near-Infrared Spectroscopy (NIRS)—a non-invasive technology that uses light to measure tissue oxygenation and brain activity—and ultrasound imaging. By using NIRS to study the brain activity associated with the sudden urge to urinate, Speich and his team are working to pinpoint the brain’s role and determine whether it or the bladder is the primary cause of an individual’s condition. “There are a lot of potential causes of overactive bladder,” says Speich. “Some people may have more than one cause. Individual responses to these treatments vary; what works well for one patient may not work at all for the next. We want to give doctors better tools for quantifying information about their patients so they can make better decisions and more optimized treatments.” Thanks to research grants, including a National Institutes of Health (NIH) grant from 2015-2025, Speich has been able to make a number of important findings in his bladder research. His team has closely examined the bladder’s dynamic elasticity, investigating the biomechanical mechanisms that allow the bladder muscle to fill and expand. Another recent focus asks, “Bladder or Brain. Which is it?” Speich and his team developed a tool called a sensation meter that they use to help determine what an individual is feeling as their bladder is filling over time. All this groundbreaking research and medical school collaboration, and to think—Speich nearly missed the opportunity to enter this field entirely. “When I tell students about how I came to be involved in bladder biomechanics, I tell them, you will always keep learning throughout your entire career,” says Speich. “You never know where you’re going to end up. If you’re an engineer, you’re a problem solver, and there are all kinds of problems in areas like business and medicine—beyond the traditional areas people think of when they think of mechanical engineering.”

2 min

VCU College of Engineering receives $4.5 million of funding for research supporting blind-visually impaired individuals

Pioneering systems to aid the visually impaired, Dianne Pawluk, Ph.D., associate professor in the Department of Biomedical Engineering, recently received two grants totaling $4.5 million in support of her research. Real-time Conversion and Display of Visual Diagrams in Accessible Forms for Blind-Visually Impaired (BVI) is a five-year project to develop real-time assistive technology for BVI individuals. It received a $3.2 million grant from the National Institutes of Health’s National Eye Institute to fund a low-cost system that will automatically convert and render visual diagrams in effective accessible formats on a multimodal display, including a refreshable tactile display and an enhanced, visual magnification program. Diagram exploration support will be provided by an automated haptic assistant. Pawluk is collaborating with Tomasz Arodz, Ph.D., associate professor in the Department of Computer Science, on the project. Including Blind and Visually Impaired Students in Computer Programming Education Through a Tangible Interface for Scratch is a four-year project to develop a nonvisual interface for the Scratch programming platform. Receiving a $1.3 million grant from the National Science Foundation, the project aims to make computer science education more accessible to BVI students. The interface will allow these students to learn programming alongside their sighted peers in classrooms, camps and clubs, supporting both BVI and other kinesthetic learners with a haptic-based tangible interface. High contrast visual information will also be provided for those with low vision and collaboration with sighted peers. This project is a collaboration with the Science Museum of Virginia, Arizona Science Center and Liberty Science Center. “Equal access to information is important for individuals who are blind or visually impaired to have autonomy and control over their decision-making processes and other tasks, which will allow them to live productive and fulfilling lives,” Pawluk said. “These projects go beyond creating an equivalent experience. They enable full collaboration between visually impaired and sighted people, ensuring equal opportunity.”

View all posts
Powered by