# High Efficiency Delivery of Surfactant Aerosols to Infants without Intubation

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $723,687

## Abstract

Surfactant replacement therapy in neonates is currently achieved through endotracheal intubation and
liquid bolus instillation. High efficiency delivery of aerosolized surfactant is proposed as a technique to improve
airway distribution of the surfactant and prevent endotracheal intubation in cases where noninvasive ventilation
(NIV) is the preferred respiratory support strategy. Primary limitations of aerosolized surfactants are currently
very low lung delivery efficiencies (typically ~1%), long delivery times (~3 hours for mesh nebulizers), and poor
distribution of the surfactant to the alveolar region.
 The goal of this study is to develop formulations and devices for the effective delivery of aerosolized
surfactants to the lungs of infants using the nose-to-lung (N2L) route thereby avoiding intubation. To achieve
high efficiency lung delivery, the excipient enhanced growth (EEG) approach will be used in which
submicrometer particles are formed through spray drying and contain the surfactant and a hygroscopic
excipient. The initial small size of the aerosolized particles allows for effective penetration through the new
delivery device and infant upper airways. Inclusion of the hygroscopic excipient in the primary particles fosters
aerosol size increase inside the airways and effective deposition in the alveolar region. This approach was
successfully employed by our group to improve N2L aerosol delivery in adults. The aerosol will be generated
using new EEG surfactant powder formulations together with new low-flow and low-volume dry powder
inhalers, which are developed and optimized using a combination of computational fluid dynamics (CFD), rapid
prototyping, and in vitro experiments. Functionality of the new surfactant aerosol will be assessed in surfactant
depletion animal models and compared with liquid instillation. The following aims are proposed to develop this
new therapeutic approach:
Specific Aim 1. Develop an excipient enhanced growth (EEG) formulation of a lung surfactant that can be
efficiently aerosolized, increase in aerodynamic size within the airways, and maintain surfactant function.
Specific Aim 2. Develop and optimize a device for generating and administering surfactant aerosols to infants
using the noninvasive nose-to-lung (N2L) route and achieving high efficiency lung delivery.
Specific Aim 3. Adapt the N2L aerosol delivery device and test EEG surfactant aerosol efficacy in an infant-
size ferret model compared with surfactant instillation in terms of oxygenation, lung distribution and histology.
Outcomes and Impact. Successful delivery of aerosolized surfactant will avoid the side effects associated
with instillation in already compromised infant airways. Efficient N2L delivery will allow for expanded use of
NIV respiratory support techniques, thereby avoiding the greater risks associated with intubation and liquid
bolus instillation. In addition to respiratory distress syndrome in infants, improved surfactant delivery to ...

## Key facts

- **NIH application ID:** 9889160
- **Project number:** 5R01HL139673-03
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Michael Hindle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $723,687
- **Award type:** 5
- **Project period:** 2018-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889160

## Citation

> US National Institutes of Health, RePORTER application 9889160, High Efficiency Delivery of Surfactant Aerosols to Infants without Intubation (5R01HL139673-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9889160. Licensed CC0.

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