Improved Respiratory Models and Lung Surfactants for Neonatal Respiratory Distress Syndrome

Technology Overview

Dr. Robert DiBlasi

Every year, approximately 1 million babies worldwide are born prematurely. In the absence of fully developed lungs, many of these premature babies lack mature lung surfactant — a complex mixture of lipids and proteins that coats and protects the inner surface of lung saccules (precursors to alveolar ducts and ultimately alveoli) and helps to keep them open during exhalation. Lung surfactant deficiency can lead to a severe form of neonatal respiratory distress syndrome (RDS), which is a major contributor to infant mortality.

Standard therapy for RDS in newborns involves delivering an expensive liquid solution of purified animal-based surfactant to the lungs, where it coats the bronchioles (the smallest airways) and saccules. The therapy necessitates an in-hospital procedure that requires placement of a breathing tube and use of a mechanical ventilator for up to several days at a time.

Artificial ventilation, however, is not without adverse side effects. It can cause lung inflammation and injury that increase the risk of complications such as retinopathy of prematurity, bronchopulmonary dysplasia, neurological injury and a spectrum of gastrointestinal disorders.

To improve both the mortality and morbidity associated with neonatal RDS and traditional therapies, respiratory therapist and pediatric pulmonary researcher Robert DiBlasi, RRT-NPS, FAARC, is working to develop an aerosolized version of lung surfactant that can be more easily delivered to premature babies and does not depend on an animal-derived formulation, intubation or a mechanical ventilator.

For the first part of that goal, DiBlasi worked with researchers from Virginia Commonwealth University to develop a delivery method that uses an inhaler device to convert a dry powder formulation into an aerosol of small particles that can be easily inhaled and targets the deep regions of the lungs. To bypass the lifesaving but often deleterious effects of mechanical ventilation, DiBlasi is investigating devices that can deliver the aerosol through the transnasal route. One device being explored is a CPAP machine that mimics the intrauterine pressure maintained by fetal lung fluid to keep the lungs open without injury.

In one project, the DiBlasi Lab is putting liquid animal-derived surfactant into a nebulizer equipped with an abdominal sensor that releases the aerosol only during inhalations to prevent excess accumulation of the surfactant in the nasal passages. Physiological and anatomical differences between infants and adults suggest that smaller aerosol particle sizes may be required to minimize upper-airway deposition and facilitate targeted delivery to the distal lungs of premature infants. However, nebulizer performance and aerosol particle size must be carefully optimized, because aerosol particles that are too small can be exhaled before depositing in the lungs. DiBlasi uses methods such as laser diffractometry and particle impactor technologies to characterize and quantify the delivered particle sizes.

To determine the most efficient delivery method, his research team is using animal models and 3D-printed, biocompatible models of infants’ upper airway anatomy — which can mimic the rapid, shallow breathing of babies and their disproportionately large nasopharyngeal cavity. This work aims to expand the field’s understanding of how surfactant travels through an infant’s airway. To increase the 3D model’s fidelity, DiBlasi is using published and bedside data to configure the model to replicate the precise breathing volumes, patterns, resistance and other characteristics of a premature baby.

The 3D model can be connected to a piston diaphragm to simulate spontaneous breathing movements and evaluate the comparative efficiency, performance and safety of different aerosol drug delivery systems. Such determinations can include how much aerosol is trapped in the upper airway or lost due to inefficiencies in the flow pathways. Branching airway models equipped with filters can directly measure the amount of aerosol delivered to the lungs. Similarly, in animal models, drug formulations radiolabeled with tags such as the chemical element technetium can be inhaled and detected with a gamma camera to provide granular information about where the drug particles go.

Although some animal models of neonatal RDS bear striking anatomic similarities in the lungs and similar breathing patterns as human neonates, these animals’ nose and nasal passageways are more complex and highly effective at filtering inhaled aerosols before reaching the lungs. To overcome this limitation, DiBlasi has developed a translational, in vivo chimera model which involves placing a 3D-printed human upper airway configuration into an animal trachea to simulate the breathing of a preterm infant with RDS. The chimera provides a more realistic preclinical model of nasal prongs and CPAP devices commonly used in babies, which can help answer key mechanical, safety and efficacy questions about transnasal delivery of surfactants and surfactant-delivery devices.

In a related effort aimed at replacing animal-derived surfactant, DiBlasi is involved in a collaborative project to develop a synthetic, dry-powder aerosol formulation of lung surfactant that avoids the issue of fluid accumulation in the upper airways as well as long treatment times. Initial results from testing done in juvenile and premature animal models suggest that this synthetic formulation rapidly achieves significantly higher blood oxygen levels and better lung mechanics than the standard hospital formulation of surfactant. DiBlasi plans to test the dry-powder surfactant formulation in additional animal models as the next step toward clinical trials in preterm infants. With his 3D-printed airway and chimera model systems recapitulating the upper airway physiology of infants, he is testing other surfactant formulations as well, including a fully synthetic liquid surfactant.

DiBlasi has extensive expertise in developing and testing neonatal and pediatric respiratory support devices, using realistic 3D-printed airways, lung simulators and physiologic animal models of respiratory disease. He also has deep experience in developing and evaluating surfactant and other medical aerosol delivery devices and medication formulations. He is interested in partnerships and collaborations that can help to further develop his model systems, evaluate new ventilation and drug delivery devices and modes and test novel surfactant formulations and other inhaled medications.

Stage of Development

• Preclinical in vitro
• Preclinical in vivo
• Preclinical ex vivo

Partnering Opportunities

• Collaborative research and development
• Sponsored research agreement
• Consultation agreement
• Clinical trials
• Data access
• Drug screening
• Computational modeling
• Animal model access
• Aerosol testing
• Lung injury testing

Learn More

• Robert DiBlasi
• DiBlasi Lab

Publications

1. Longest W, Hindle M, Farkas D … DiBlasi RM. Preclinical testing of a new dry powder aerosol synthetic lung surfactant formulation and device combination for the treatment of neonatal respiratory distress syndrome. J Aerosol Med Pulm Drug Deliv. 2025;38(4):168-191.
2. Kontoudios N, KenKnight HR, DiBlasi RM. In vitro comparison of aerosol delivery in high-frequency assisted airway clearance devices with integrated nebulizers. Respir Care. 2024;69(10):1221-1230.
3. DiBlasi RM, Engberg RJ, Poli J, et al. Aerosol delivery efficiency with high-flow nasal cannula therapy in neonatal, pediatric, and adult nasal upper-airway and lung models. Respir Care. 2024;69(9):1146-1160.
4. DiBlasi RM, KenKnight H, Kontoudios N, et al. Development of a new dry powder aerosol synthetic lung surfactant product for neonatal respiratory distress syndrome (RDS)–Part II: in vivo efficacy testing in a rabbit surfactant washout model. Pharm Res. 2024;41(9):1827-1842.
5. Momin MA, Farkas D … DiBlasi RM, Longest W. Development of a new dry powder aerosol synthetic lung surfactant product for neonatal respiratory distress syndrome (RDS)–Part I: In vitro testing and characterization. Pharm Res. 2024;41(8):1703-1723.
6. DiBlasi RM, Micheletti KJ, Romo T, et al. Evaluation of lung volumes and gas exchange in surfactant-deficient rabbits between variable and fixed servo pressures during high-frequency jet ventilation. J Perinatol. 2024;44(2):266-272.
7. DiBlasi RM, Crandall CN, Engberg RJ, et al. Evaluation of a novel dry powder surfactant aerosol delivery system for use in premature infants supported with bubble CPAP. Pharmaceutics. 2023;15(10):2368.
8. Walther FJ, Waring AJ, Otieno M, DiBlasi RM. Efficacy, dose–response, and aerosol delivery of dry powder synthetic lung surfactant treatment in surfactant-deficient rabbits and premature lambs. Respir Res. 2022;23(1):78.

Article last updated September 17, 2026