title: Biodistribution of size-selected lyophilisomes in mice.
abstract: Lyophilisomes are a novel class of proteinaceous biodegradable nano/microparticle capsules developed for tumor drug delivery. The in vivo characteristics of lyophilisomes are unknown and, therefore, the time course of biodistribution of sized albumin-based lyophilisomes in CD1 mice after intravenous administration was studied. Lyophilisomes, prepared from Dylight680-labeled albumin, were sized using a sucrose gradient centrifugation methodology and four fractions with a mean size of approximately 200nm, 400nm, 550nm, and 650nm were pooled for in/ex vivo localization, (immuno)histochemistry and biochemical analysis. Lyophilisomes were rapidly taken out of the circulation by the liver and spleen. Immunohistochemistry revealed that lyophilisomes were taken up in the liver by F4/80 positive macrophages, and in the spleen by Sign-R1 positive macrophages specifically located in the marginal zones. Lyophilisomes were most likely degraded by the liver and spleen and subsequently excreted via the urine, as high levels of degraded Dylight680-labeled albumin were detected in the urine. This was corroborated by electron microscopy of the spleen, which showed intact lyophilisomes in the marginal zone 5 and 30min after injection, but not after 2h. In conclusion, IV injected lyophilisomes are rapidly entrapped by liver and splenic macrophages, biodegraded, and excreted in the urine.
authors.affiliation: Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Biochemistry, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: Etienne.vanBracht@Radboudumc.nl.
authors.forename: Etienne
authors.initials: E
authors.lastname: van Bracht
authors.affiliation: Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Biochemistry, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: Rene.Raave@Radboudumc.nl.
authors.forename: René
authors.initials: R
authors.lastname: Raavé
authors.affiliation: Department of Molecular Biophysics and Physics of Polymers, St. Petersburg State University, Ulianovskaya Str. 1, 198504 St. Petersburg, Russia. Electronic address: Igor.Perevyazko@uni-jena.de.
authors.forename: Igor Y
authors.initials: IY
authors.lastname: Perevyazko
authors.affiliation: Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Biochemistry, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: Elly.Versteeg@Radboudumc.nl.
authors.forename: Elly M
authors.initials: EM
authors.lastname: Versteeg
authors.affiliation: Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Biochemistry, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: Theo.Hafmans@Radboudumc.nl.
authors.forename: Theo G
authors.initials: TG
authors.lastname: Hafmans
authors.affiliation: Friedrich Schiller University Jena, Laboratory of Organic and Macromolecular Chemistry (IOMC), Humboldtstr. 10, 07743 Jena, Germany; Friedrich Schiller University Jena, Jena Center for Soft Matter (JCSM), Philosophenweg 7, 07743 Jena, Germany; Dutch Polymer Institute (DPI), P.O. Box 902, 5600 AX Eindhoven, The Netherlands. Electronic address: Ulrich.Schubert@uni-jena.de.
authors.forename: Ulrich S
authors.initials: US
authors.lastname: Schubert
authors.affiliation: Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Urology, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: Egbert.Oosterwijk@Radboudumc.nl.
authors.forename: Egbert
authors.initials: E
authors.lastname: Oosterwijk
authors.affiliation: Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Biochemistry, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: Toin.vanKuppevelt@Radboudumc.nl.
authors.forename: Toin H
authors.initials: TH
authors.lastname: van Kuppevelt
authors.affiliation: Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Biochemistry, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: Willeke.Daamen@Radboudumc.nl.
authors.forename: Willeke F
authors.initials: WF
authors.lastname: Daamen
mesh_terms: D061605:Administration, Intravenous; D000418:Albumins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D002499:Centrifugation, Density Gradient; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D000067493:Dynamic Light Scattering; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007150:Immunohistochemistry; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D010316:Particle Size; D059748:Proteolysis; D065667:Renal Elimination; D013154:Spleen / Q000378:metabolism / Q000648:ultrastructure; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution
chemical_list: D000418:Albumins; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008055:Lipids
keywords: Albumin; Biodistribution; Drug delivery; Lyophilisomes; Nanocapsules; Sucrose gradient; Ultracentrifugation