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Albumin-based nanoparticles as magnetic resonance contrast agents: II. Physicochemical characterisation of purified and standardised nanoparticles

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Abstract

We are developing a nanoparticulate histochemical reagent designed for histochemistry in living animals (molecular imaging), which should finally be useful in clinical imaging applications. The iterative development procedure employed involves conceptual design of the reagent, synthesis and testing of the reagent, then redesign based on data from the testing; each cycle of testing and development generates a new generation of nanoparticles, and this report describes the synthesis and testing of the third generation. The nanoparticles are based on human serum albumin and the imaging modality selected is magnetic resonance imaging (MRI). Testing the second particle generation with newly introduced techniques revealed the presence of impurities in the final product, therefore we replaced dialysis with diafiltration. We introduced further testing methods including thin layer chromatography, arsenazo III as chromogenic assay for gadolinium, and several versions of polyacrylamide gel electrophoresis, for physicochemical characterisation of the nanoparticles and intermediate synthesis compounds. The high grade of chemical purity achieved by combined application of these methodologies allowed standardised particle sizes to be achieved (low dispersities), and accurate measurement of critical physicochemical parameters influencing particle size and imaging properties. Regression plots confirmed the high purity and standardisation. The good degree of quantitative physicochemical characterisation aided our understanding of the nanoparticles and allowed a conceptual model of them to be prepared. Toxicological screening demonstrated the extremely low toxicity of the particles. The high magnetic resonance relaxivities and enhanced mechanical stability of the particles make them an excellent platform for the further development of MRI molecular imaging.

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Acknowledgments

The Austrian Nano-Initiative, the Austrian Science Foundation (FWF) (Project N201-NAN) and the Austrian National Bank Jubilee Programme supported this work (Projects 9273, 10844, 11574 and 13096).

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  1. A. A. Abdelmoez

    Present address: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt

Authors and Affiliations

  1. Department of Radiology, Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria

    A. A. Abdelmoez, G. C. Thurner, E. A. Wallnöfer, C. Kremser & W. Jaschke

  2. Department of Anatomy, Histology and Embryology, Innsbruck Medical University, Müllerstrasse 59, 6020, Innsbruck, Austria

    N. Klammsteiner & P. Debbage

  3. Biozentrum of the Medical University Innsbruck, Section for Clinical Biochemistry, Fritz-Pregl-Straße 3, 6020, Innsbruck, Austria

    H. Talasz

  4. Center for Medical Research, Stiftingtalstrasse 24, 8010, Graz, Austria

    M. Mrakovcic & E. Fröhlich

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  1. A. A. Abdelmoez
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Correspondence to P. Debbage.

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A. A. Abdelmoez and G. C. Thurner contributed equally to this work.

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Abdelmoez, A.A., Thurner, G.C., Wallnöfer, E.A. et al. Albumin-based nanoparticles as magnetic resonance contrast agents: II. Physicochemical characterisation of purified and standardised nanoparticles. Histochem Cell Biol 134, 171–196 (2010). https://doi.org/10.1007/s00418-010-0726-6

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