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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.

SUBMITTER: El-Gendy N

PROVIDER: S-EPMC2859999 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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

El-Gendy Nashwa N Aillon Kristin L KL Berkland Cory C

International journal of pharmaceutics 20100307 1-2

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 ma ...[more]

PMID: 20214960

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Project description:In the tumor micro-environment, tumor associated macrophages (TAMs) represent a predominant component of the total tumor mass, and TAMs play a complex and diverse role in cancer pathogenesis with potential for either tumor suppressive, or tumor promoting biology. Thus, understanding macrophage localization and function are essential for cancer diagnosis and treatment. Typically, tissue biopsy is used to evaluate the density and polarization of TAMs, but provides a limited "snapshot" in time of a dynamic and potentially heterogeneous tumor immune microenvironment. Imaging has the potential for three-dimensional mapping; however, there is a paucity of macrophage-targeted contrast agents to specifically detect TAM subtypes. We have previously found that sulfated-dextran coated iron oxide nanoparticles (SDIO) can target macrophage scavenger receptor A (SR-A, also known as CD204). Since CD204 (SR-A) is considered a biomarker for the M2 macrophage polarization, these SDIO might provide M2-specific imaging probes for MRI. In this work, we investigate whether SDIO can label M2-polarized cells in vitro. We evaluate the effect of degree of sulfation on uptake by primary cultured bone marrow derived macrophages (BMDM) and found that a higher degree of sulfation led to higher uptake, but there were no differences across the subtypes. Further analysis of the BMDM showed similar SR-A expression across stimulation conditions, suggesting that this classic model for macrophage subtypes may not be ideal for definitive M2 subtype marker expression, especially SR-A. We further examine the localization of SDIO in TAMs in vivo, in the mammary fat pad mouse model of breast cancer. We demonstrate that uptake by TAMs expressing SR-A scales with degree of sulfation, consistent with the in vitro studies. The TAMs demonstrate M2-like function and secrete Arg-1 but not iNOS. Uptake by these M2-like TAMs is validated by immunohistochemistry. SDIO show promise as a valuable addition to the toolkit of imaging probes targeted to different biomarkers for TAMs.

Dataset Information

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

Publications

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

Similar Datasets

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