The delivery of aerosolized medications to neonates and infants on mechanical ventilation is expected to provide a number of benefits including increased drug concentrations at the site of action within the airways, improved drug efficacy, and reduced side effects. Presently, clinical outcomes of aerosol therapy delivered to infants for a variety of medical conditions are often disappointing or inconclusive. Current aerosol generation techniques for use with neonates and infants on mechanical ventilation have been shown to deliver approximately 1% or less of the initial dose to the lungs. It is believed that aerosolized medicines delivered to infants are often ineffective because of low delivery efficiencies and high dose variability. The objective of this study is to develop a new wick-based electrospray system (WES) for highly efficient delivery of electrostatically charged submicrometer and nanometer scale aerosols to the respiratory airways of neonates and infants during invasive mechanical ventilation. In contrast with previous devices for aerosol delivery, the WES system is intended to generate aerosols in the submicrometer (<1000 nm) and nanometer (<100 nm) size regimes. The small size of the aerosol droplets will dramatically reduce deposition in the delivery lines and allow a large fraction of the dose to enter the airways. Once inside the lungs, the inherent charge of the electrospray droplets as well as Brownian motion of the nanometer aerosol will foster enhanced deposition and ensure almost complete lung retention. Compared with conventional electrospray, the WES device replaces the syringe pump and capillary with a porous polymer wick, which reduces device cost and complexity. Furthermore, the corona needle of typical electrospray devices is removed, which eliminates the formation of ozone. In order to develop this novel device for respiratory drug delivery, the following specific aims are proposed.
Specific Aim 1 : Develop a polymer-based wick electrospray (WES) system for generating and delivering charged submicrometer and nanometer pharmaceutical aerosols.
Specific Aim 2 : Optimize the performance of the WES system in terms of increasing the aerosol output rate and minimizing deposition within the device and delivery lines.
Specific Aim 3 : Evaluate the transport and deposition of WES aerosols in the respiratory airways of infants using in vitro experiments and CFD simulations. The proposed device will provide, for the first time, a source of submicrometer droplets with minimal device and delivery line deposition (<20-30%) and full lung retention of the aerosol, which represents a 1 to 2 order of magnitude improvement compared with current devices. Potential applications where improved delivery efficiency to the lungs, reduced dose variability, and deposition within the entire airways of infants are of critical importance include the use of aerosolized surfactants, antibiotics, prostanoids, and diuretics.

Public Health Relevance

Current devices for delivering aerosolized medicines to infants on mechanical ventilation lose a large amount of the administered dose in the connective tubing, such that only approximately 1% of the drug reaches the patient's lungs. In this study, polymer wicks and electrospray are combined to produce nanometer-scale aerosols that increase delivery efficiency to the lungs by a factor ranging between 10 and 100 compared with conventional systems. It is expected that improving delivery efficiency and reducing variability in dose will make many current inhaled medications more effective and may allow for the use of inhaled antibiotics and surfactants in infants.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Exploratory/Developmental Grants (R21)
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Gene and Drug Delivery Systems Study Section (GDD)
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Raju, Tonse N
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Virginia Commonwealth University
Engineering (All Types)
Schools of Engineering
United States
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Golshahi, Laleh; Longest, P Worth; Holbrook, Landon et al. (2015) Production of Highly Charged Pharmaceutical Aerosols Using a New Aerosol Induction Charger. Pharm Res 32:3007-17
Holbrook, Landon; Hindle, Michael; Longest, P Worth (2015) Generating Charged Pharmaceutical Aerosols Intended to Improve Targeted Drug Delivery in Ventilated Infants. J Aerosol Sci 88:35-47
Longest, P Worth; Tian, Geng (2015) Development of a new technique for the efficient delivery of aerosolized medications to infants on mechanical ventilation. Pharm Res 32:321-36
Longest, P Worth; Azimi, Mandana; Hindle, Michael (2014) Optimal delivery of aerosols to infants during mechanical ventilation. J Aerosol Med Pulm Drug Deliv 27:371-85