Newborns who lack natural surfactants develop respiratory distress syndrome.
Surfactants are materials that reduce liquid surface tension, enabling carbon dioxide and oxygen to easily exchange as lungs expand and contract, oxygenating blood and facilitating the body’s natural functions.
A VCU team received a $3 million grant from the Bill & Melinda Gates Foundation to create an aerosolized surfactant and a device to deliver the surfactant. Dr. Worth Longest and his team are developing an affordable, noninvasive treatment for RDS. Current treatment is through external therapy but the cost, complexity and invasiveness of the procedure make it inaccessible for many, especially infants in low- and middle-income countries.
The need for an affordable treatment option led Longest, the Louis S. and Ruth S. Harris Exceptional Scholar Professor in the Department of Mechanical and Nuclear Engineering in the College of Engineering, Dr. Hindle, Peter R. Byron Distinguished Professor at the VCU School of Pharmacy and Rob DiBlasi, leading clinical researcher and principal investigator at Seattle Children’s Research Institute, to seek funding from the Gates Foundation to develop an aerosol drug formulation and delivery mechanism for a synthetic lung surfactant capable of being delivered anywhere, with minimal equipment and at a reasonable cost.
“Some physicians regard aerosolized surfactant delivery as an obvious need in neonatal respiratory care,” Longest said. “It’s been envisioned for many years, but has not been realized due to a number of obstacles.”
Current RDS treatments require sedation of the patient for intubation and instillation of liquid surfactant into the lungs. If surfactant administration is available, doctors must weigh additional risk exposures prior to making the decision to give surfactant even when it is likely to be beneficial. When combined with the need for specialized equipment operating in a sterile, temperature-controlled environment, access to this life-saving treatment becomes inaccessible due to cost, availability of proper facilities or both.
Challenges include delivering an effective dosage of the aerosol formulation. Current dry powder inhalers require more air to operate effectively than can be administered to an infant who have smaller lung capacity. Inhalers are limited to approximately 1 milligram of medication, which is significantly less than the required dosage for surfactant treatment.
Longest and Hindle will create an effective delivery method by using 3D-printed upper respiratory pathway models and testing the effectiveness of a dispersal mechanism to ensure the dry powder formulation is being delivered deep within the lungs at the required high dosage.
Longest and Hindle previously developed inline dry powder inhalers to demonstrate the capacity to achieve proper powder formulation dispersion with a low air volume. Their teams received a patent for the technology in July and are applying the same strategy to a surfactant formulation that can be aerosolized.
“Because these delivery mechanisms are strongly linked to the drug formulations they are designed to administer, it’s important to perform this kind of research simultaneously and in an iterative manner,” Longest said. “My lab collaborates with Dr. Hindle’s lab on a daily basis to solve this and other challenging problems in the field of pharmaceutical aerosols.”
Work is currently underway with refinement of the delivery mechanism, followed by validation using computational fluid dynamics and concurrent lab testing to explore different design alternatives. The goal is a high-efficiency rapid aerosol delivery product that can fully restore an infant’s blood gas levels and be administered as a stand-alone therapy in less than one minute, or simultaneously during nasal continuous positive airway pressure, or CPAP, therapy.
The team will also employ unique 3D-printed airway models that replicate the anatomy of preterm infants with the goal of expanding the age range of treatment and preparation for commercial production. The team will concurrently develop a larger spray-drying system for producing the dry powder surfactant formula. The proposed devices, strategy and formulation are also based on earlier and ongoing work by Longest and Hindle funded by the National Institutes of Health.
“Though we have a strong foundation for what we want to accomplish, there is much work to be done,” Longest said. “This is a multi-year project that will involve collaboration between several teams with a focus on developing treatment accessible to low-resource populations, which will be supported by grant funding from the Gates Foundation.”
Two former VCU undergraduates, Dale Farkas and Sarah Strickler, returned to VCU as part of the mechanical and nuclear engineering Ph.D. program and joined the team.
“As an engineer, I want to use my training to have a positive impact on people’s lives,” Longest said. “Many elements of my skill set line up well with the treatment of respiratory diseases, and I came to VCU almost 20 years ago based on the opportunity to work with the School of Pharmacy Aerosol Group, including Drs. Hindle and Peter Bryon, who is now retired, as well as the chance to be a part of a young and growing engineering program.”
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Rebecca Barnabi
