Dry powdered aerosols of diatrizoic acid nanoparticle agglomerates as a lung contrast agent

Abstract

Aerosolized contrast agents may improve the resolution of biomedical imaging modalities and enable more accurate diagnosis of lung diseases. Many iodinated compounds, such as diatrizoic acid, have been shown to be safe and useful for radiographic examination of the airways. Formulations of such compounds must be improved in order to allow imaging of the smallest airways. Here, diatrizoic acid nanoparticle agglomerates were created by assembling nanoparticles into inhalable microparticles that may augment deposition in the lung periphery. Nanoparticle agglomerates were fully characterized and safety was determined in vivo. After dry powder insufflation to rats, no acute alveolar tissue damage was observed 2h post-dose. Diatrizoic acid nanoparticle agglomerates possess the characteristics of an efficient and safe inhalable lung contrast agent.

Figure 1

The particle size distributions of diatrizoic acid nanoparticle agglomerates D9 after flocculation and resuspended after lyophilization.

Figure 2

Aerodynamic size distributions of diatrizoic acid nanoparticle agglomerates D9 after lyophilization.

Figure 3

The distribution of diatrizoic acid powder as received as well as nanoparticle agglomerate formulation (D9) deposited on the stages of a cascade impactor at a flow rate of ~30 L/min.

Figure 4

Transmission electron micrographs of diatrizoic acid A) D9 nanoparticles and B) D9 nanoparticle agglomerates.

Figure 5

Differential scanning calorimetry (DSC) thermograms for diatrizoic acid as received, nanoparticles (NP), nanoparticle agglomerates (NA) and l-leucine as received.

Figure 6

Thermogravimetric analysis (TGA) for diatrizoic acid as received, nanoparticles (NP) and nanoparticle agglomerates (NA).

Figure 7

Dissolution profiles of diatrizoic acid in PBS (pH 7.4) from diatrizoic acid powder as received, the prepared D9 nanoparticle (NP) and nanoparticle agglomerate formulation (NA).

Figure 8

Rat right lung histology images A) after 10 mg insufflation of D9 nanoparticle agglomerates (2 h post dose) and B) normal lung tissue, no insufflation.