4.7 Article

Iodinated Nano Clusters as an Inhaled Computed Tomography Contrast Agent for Lung Visualization

Journal

MOLECULAR PHARMACEUTICS
Volume 7, Issue 4, Pages 1274-1282

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/mp1000718

Keywords

NanoCluster; contrast agent; particle engineering; CT imaging; N1177; aerosol

Funding

  1. Savara Pharmaceuticals
  2. Cystic Fibrosis Foundation
  3. Coulter Foundation
  4. Higuchi Biosciences Center
  5. American Heart Association
  6. NIH [R03 AR054035, P20 RR016443, T32 GM08359-11]
  7. Department of Defense
  8. W.M. Keck Foundation
  9. NCI Cancer Center [P30CA118100-06]
  10. Div Of Chem, Bioeng, Env, & Transp Sys
  11. Directorate For Engineering [0966614] Funding Source: National Science Foundation

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Improvements to contrast media formulations may be an effective way to increase the accuracy and effectiveness of thoracic computed tomography (CT) imaging in disease evaluation. To achieve contrast enhancement in the lungs, a relatively large localized concentration of contrast media must be delivered. Inhalation offers a noninvasive alternative to intrapleural injections for local lung delivery, but effective aerosolization may deter successful imaging strategies. Here, NanoCluster technology was applied to N1177, a diatrizoic acid derivative, to formulate low density nanoparticle agglomerates with aerodynamic diameters 5 pm. Excipient-free N1177 NanoCluster powders were delivered to rats by insufflation or inhalation and scanned using CT up to 1 h post dose. CT images after inhalation showed a similar to 120 (HU) Hounsfield units contrast increase in the lungs, which was more than sufficient contrast for thoracic CT imaging. Lung tissue histology demonstrated that N1177 NanoClusters did not damage the lungs. NanoCluster particle engineering technology offers a novel approach to safely and efficiently disseminate high concentrations of contrast agents to the lung periphery.

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