1Faculty of Health and Society, Malmö University, 205 06 Malmö, Sweden. 2Institute of Inorganic Chemistry, University of Vienna, Währinger Str. 42, 1090 Vienna, Austria. 3Department of Radiology, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. 4Section for Clinical Biochemistry, Biozentrum of the Medical University Innsbruck, Fritz-Pregl-Straße 3, 6020 Innsbruck, Austria. 5Department of Anatomy, Histology and Embryology, Innsbruck Medical University, Mu¨llerstrasse 59, 6020 Innsbruck, Austria. 6Department of Nuclear Medicine, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria. 7Center for Medical Research, Stiftingtalstrasse 24, 8010 Graz, Austria. 8Division of Neuroanatomy, Department of Anatomy, Histology and Embryology, Innsbruck Medical University, Müllerstrasse 59, 6020 Innsbruck, Austria. 9Current address: Department of Pharmaceutical Organic Chemistry, Assiut University, Assiut, Egypt

To develop a platform for molecular magnetic resonance imaging, we prepared gadolinium-bearing albumin-polylactic acid nanoparticles in the size range 20–40 nm diameter. Iterative cycles of design and testing upscaled the synthesis procedures to gram amounts for physicochemical characterisation and for pharmacokinetic testing. Morphological analyses showed that the nanoparticles were spheroidal with rough surfaces. Particle sizes were measured by direct transmission electron microscopical measurements from negatively contrasted preparations, and by use of photon correlation spectroscopy; the two methods each documented nanoparticle sizes less than 100 nm and generally 10–40 nm diameter, though with significant intrabatch and interbatch variability. The particles’ charge sufficed to hold them in suspension. HSA retained its tertiary structure in the particles. The nanoparticles were stable against turbulent flow conditions and against heat, though not against detergents. MRI imaging of liquid columns was possible at nanoparticle concentrations below 10 mg/ml. The particles were non-cytotoxic, non-thrombogenic and non-immunogenic in a range of assay systems developed for toxicity testing of nanoparticles. They were micellar prior to lyophilisation, but loosely structured aggregated masses after lyophilisation and subsequent resuspension. These nanoparticles provide a platform for further development, based on non-toxic materials of low immunogenicity already in clinical use, not expensive, and synthesized using methods which can be upscaled for industrial production.