title: How stealthy are PEG-PLA nanoparticles? An NIR in vivo study combined with detailed size measurements.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schädlich
authors.forename: Cornelia
authors.initials: C
authors.lastname: Rose
authors.forename: Judith
authors.initials: J
authors.lastname: Kuntsche
authors.forename: Henrike
authors.initials: H
authors.lastname: Caysa
authors.forename: Thomas
authors.initials: T
authors.lastname: Mueller
authors.forename: Achim
authors.initials: A
authors.lastname: Göpferich
authors.forename: Karsten
authors.initials: K
authors.lastname: Mäder
mesh_terms: D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D004355:Drug Stability; D005260:Female; D031521:Fractionation, Field Flow / Q000379:methods; D008297:Male; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission / Q000379:methods; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics*; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols