A Trans-Nasal Aerosol Delivery Device for Efficient Pulmonary Deposition.
BACKGROUND
Efficient delivery of aerosols to the lungs via the nasal route has been difficult to achieve, but it may offer benefits over the traditional oral route for a range of patient populations. Because slow, continuous delivery of short-acting agents could improve safety, tolerability, compliance, and efficacy when compared with the rapid, intermittent aerosol treatments delivered by mouthpiece or mask, a novel trans-nasal pulmonary aerosol delivery (tPAD) device was developed. The tPAD incorporates an aerosol particle-size selection chamber and a custom nasal cannula that are specifically optimized for aerosol delivery to the lung via the nasal route. The tPAD device produced a steady aerosol output (∼2 mL/h) from an optimized nasal cannula with negligible rainout in the cannula for up to 8 hours. The generated aerosol particles were small enough to minimize nasal deposition [volume median diameter (VMD) = 1.4 μm].


METHODS
In this proof-of-concept study, gamma scintigraphy was used to quantitate deposition efficiency of99mTc-labeled DTPA in 7% NaCl (hypertonic saline) in healthy human subjects (n = 6) during a short dosing period (15 minutes). A comparison was made with a standard oral jet nebulizer in the same subjects.


RESULTS
The tPAD device achieved high pulmonary deposition (39% ± 8%), based on emitted dose, and matched that of the oral jet nebulizer (36% ± 9%). Low fractions of aerosol deposition in the head and nose region were observed for tPAD (6% ± 6%) and jet nebulizer deliver (1% ± 1%) as well.


CONCLUSIONS
A profile of high pulmonary deposition efficiency and low nasal dose may enable the sustained use of the tPAD platform with a variety of therapeutic agents for a range of pulmonary disorders.
1 University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, Marsico Lung Institute.
Kirby L
KL
Zeman
1 University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, Marsico Lung Institute.
Juan Rojas
JR
Balcazar
1 University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, Marsico Lung Institute.
Fred
F
Fuller
2 Parion Sciences, Inc. , Durham, North Carolina.
Karl H
KH
Donn
1 University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, Marsico Lung Institute.
Richard C
RC
Boucher
1 University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, Marsico Lung Institute.
William D
WD
Bennett
1 University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, Marsico Lung Institute.
Scott H
SH
Donaldson
D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000328:Adult; D000336:Aerosols / Q000008:administration & dosage; D000072601:Cannula; D018592:Cross-Over Studies; D016503:Drug Delivery Systems; D004867:Equipment Design; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008397:Masks; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage; D016284:Technetium Tc 99m Pentetate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution
D000336:Aerosols; D019275:Radiopharmaceuticals; D012462:Saline Solution, Hypertonic; D016284:Technetium Tc 99m Pentetate
aerosol deposition; hypertonic saline; nasal delivery