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How Stealthy are PEG-PLA Nanoparticles? An NIR In Vivo Study Combined with Detailed Size Measurements

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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.

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Abbreviations

AF4:

asymmetrical field flow field fractionation

CHO:

Chinese hamster ovary

DiR:

1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide

EMEM:

Eagle’s minimum essential medium

EPR:

enhanced permeability and retention

FBS:

fetal bovine serum

MALLS:

multi-angle laser light scattering

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NIR:

near infrared

NR:

nile red

PBS:

phosphate-buffered saline

PCS:

photon correlation spectroscopy

PDI:

polydispersity indices

QD:

quantum dots

RES:

reticuloendothelial system

ROI:

region of interest

TEM:

transmission electron microscopy

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ACKNOWLEDGMENTS

Jörg Teßmar is acknowledged for the discussions during the polymer synthesis and nanoparticle preparation steps. We also thank also Anna Hezinger for the help with the TEM measurements and Martina Hennicke and Constanze Gottschalk for taking care of the animals. Parts of the studies were supported by grants from the Federal State of Saxony Anhalt (FKZ 3646A/0907).

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Authors and Affiliations

  1. Department of Pharmaceutical Technology and Biopharmaceutics, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120, Halle (Saale), Germany

    Andreas Schädlich, Judith Kuntsche & Karsten Mäder

  2. Department of Pharmaceutical Technology, University of Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany

    Cornelia Rose & Achim Göpferich

  3. Department of Internal Medicine IV, Oncology/Hematology, Martin Luther University Halle-Wittenberg, 06120, Halle (Saale), Germany

    Henrike Caysa & Thomas Mueller

Authors
  1. Andreas Schädlich
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  2. Cornelia Rose
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Correspondence to Karsten Mäder.

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Schädlich, A., Rose, C., Kuntsche, J. et al. How Stealthy are PEG-PLA Nanoparticles? An NIR In Vivo Study Combined with Detailed Size Measurements. Pharm Res 28, 1995–2007 (2011). https://doi.org/10.1007/s11095-011-0426-5

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  • DOI: https://doi.org/10.1007/s11095-011-0426-5

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