title: Dextran-based therapeutic nanoparticles for hepatic drug delivery.
abstract: OBJECTIVE
  Evaluation of dextran-based nanoparticles (DNP) as a drug delivery system to target myeloid cells of the liver.
  
  
  METHODS
  DNP were synthesized and optionally PEGylated. Their toxicity and cellular uptake were studied in vitro. Empty and siRNA-carrying DNP were tested in vivo with regard to biodistribution and cellular uptake.
  
  
  RESULTS
  In vitro, DNP were taken up by cells of the myeloid lineage without compromising their viability. In vivo, empty and siRNA-carrying DNP distributed to the liver where a single treatment addressed approximately 70% of macrophages and dendritic cells. Serum parameters indicated no in vivo toxicity.
  
  
  CONCLUSIONS
  DNP are multifunctional liver-specific drug carriers which lack toxic side effects and may be utilized in clinical applications targeting liver macrophages.
authors.affiliation: Institute of Translational Immunology & Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.|Department of Medicine I, University Medical Center, Mainz, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Foerster
authors.affiliation: Institute of Pharmacy & Biochemistry, Johannes Gutenberg-University Mainz, Staudingerweg 5, Mainz, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Bamberger
authors.affiliation: Department of Dermatology, University Medical Center, Mainz, Germany.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Schupp
authors.affiliation: Department of Dermatology, University Medical Center, Mainz, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Weilbächer
authors.affiliation: Institute of Translational Immunology & Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
authors.forename: Leonard
authors.initials: L
authors.lastname: Kaps
authors.affiliation: Institute of Translational Immunology & Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Strobl
authors.affiliation: Institute of Pharmacy & Biochemistry, Johannes Gutenberg-University Mainz, Staudingerweg 5, Mainz, Germany.
authors.forename: Lydia
authors.initials: L
authors.lastname: Radi
authors.affiliation: TRON - Translational Oncology at the University Medical Center of Johannes Gutenberg University Mainz gGmbH, Freiligrathstraße 12, 55131 Mainz, Germany.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Diken
authors.affiliation: Department of Medicine I, University Medical Center, Mainz, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Strand
authors.affiliation: Department of Dermatology, University Medical Center, Mainz, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tuettenberg
authors.affiliation: Institute of Pharmacy & Biochemistry, Johannes Gutenberg-University Mainz, Staudingerweg 5, Mainz, Germany.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Wich
authors.affiliation: Institute of Translational Immunology & Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.|Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism; D003911:Dextrans / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D000067996:RAW 264.7 Cells; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D013499:Surface Properties; D014018:Tissue Distribution; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003911:Dextrans; D004337:Drug Carriers; D011092:Polyethylene Glycols; D034741:RNA, Small Interfering; C081026:CD68 protein, mouse; D000097382:CD68 Molecule
keywords: PEGylation; biodegradable; dendritic cell; dextran; drug delivery; liver targeting; macrophage; nanoparticles; siRNA