caa a22 4500 445313625 CHVBK 20180317142638.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s11095-011-0426-5 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0426-5 How Stealthy are PEG-PLA Nanoparticles? An NIR In Vivo Study Combined with Detailed Size Measurements [Elektronische Daten] [Andreas Schädlich, Cornelia Rose, Judith Kuntsche, Henrike Caysa, Thomas Mueller, Achim Göpferich, Karsten Mäder] ABSTRACT: Purpose: Detailed in vivo and ex vivo analysis of nanoparticle distribution, accumulation and elimination processes were combined with comprehensive particle size characterizations. Methods: The in vivo fate of near infrared (NIR) nanoparticles in nude mice was carried out using the Maestro™ in vivo fluorescence imaging system. Asymmetrical field flow field fractionation (AF4) coupled with multi-angle laser light scattering (MALLS), photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM) were employed for detailed in vitro characterization. Results: PEG-PLA block polymers were synthesized and used for the production of defined, stable, nontoxic nanoparticles. Nanoparticle analysis revealed narrow size distribution; AF4/MALLS permitted further accurate size evaluation. Multispectral fluorescence imaging made it possible to follow the in vivo fate non-invasively even in deep tissues over several days. Detailed fluorescence ex vivo imaging studies were performed and allowed to establish a calculation method to compare nanoparticle batches with varying fluorescence intensities. Conclusion: We combined narrow-size distributed nanoparticle batches with detailed in vitro characterization and the understanding of their in vivo fate using fluorescence imaging, confirming the wide possibilities of the non-invasive technique and presenting the basis to evaluate future size-dependent passive tumor accumulation studies. Springer Science+Business Media, LLC, 2011 AF4 nationallicence fluorescence imaging nationallicence in vivo imaging nationallicence nanoparticle nationallicence PEG-PLA nationallicence AF4 : asymmetrical field flow field fractionation nationallicence CHO : Chinese hamster ovary nationallicence DiR : 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide nationallicence EMEM : Eagle's minimum essential medium nationallicence EPR : enhanced permeability and retention nationallicence FBS : fetal bovine serum nationallicence MALLS : multi-angle laser light scattering nationallicence MTT : 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide nationallicence NIR : near infrared nationallicence NR : nile red nationallicence PBS : phosphate-buffered saline nationallicence PCS : photon correlation spectroscopy nationallicence PDI : polydispersity indices nationallicence QD : quantum dots nationallicence RES : reticuloendothelial system nationallicence ROI : region of interest nationallicence TEM : transmission electron microscopy nationallicence Schädlich Andreas Department of Pharmaceutical Technology and Biopharmaceutics, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120, Halle (Saale), Germany aut Rose Cornelia Department of Pharmaceutical Technology, University of Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany aut Kuntsche Judith Department of Pharmaceutical Technology and Biopharmaceutics, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120, Halle (Saale), Germany aut Caysa Henrike Department of Internal Medicine IV, Oncology/Hematology, Martin Luther University Halle-Wittenberg, 06120, Halle (Saale), Germany aut Mueller Thomas Department of Internal Medicine IV, Oncology/Hematology, Martin Luther University Halle-Wittenberg, 06120, Halle (Saale), Germany aut Göpferich Achim Department of Pharmaceutical Technology, University of Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany aut Mäder Karsten Department of Pharmaceutical Technology and Biopharmaceutics, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120, Halle (Saale), Germany aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1995-2007 0724-8741 28:8<1995 2011 28 11095 https://doi.org/10.1007/s11095-011-0426-5 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0426-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Schädlich Andreas Department of Pharmaceutical Technology and Biopharmaceutics, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120, Halle (Saale), Germany aut NATIONALLICENCE 700 1- Rose Cornelia Department of Pharmaceutical Technology, University of Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany aut NATIONALLICENCE 700 1- Kuntsche Judith Department of Pharmaceutical Technology and Biopharmaceutics, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120, Halle (Saale), Germany aut NATIONALLICENCE 700 1- Caysa Henrike Department of Internal Medicine IV, Oncology/Hematology, Martin Luther University Halle-Wittenberg, 06120, Halle (Saale), Germany aut NATIONALLICENCE 700 1- Mueller Thomas Department of Internal Medicine IV, Oncology/Hematology, Martin Luther University Halle-Wittenberg, 06120, Halle (Saale), Germany aut NATIONALLICENCE 700 1- Göpferich Achim Department of Pharmaceutical Technology, University of Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany aut NATIONALLICENCE 700 1- Mäder Karsten Department of Pharmaceutical Technology and Biopharmaceutics, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120, Halle (Saale), Germany aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 1995-2007 0724-8741 28:8<1995 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer