title: Carbohydrate plasma expanders for passive tumor targeting: in vitro and in vivo studies.
abstract: The objective of this study was to investigate the suitability of carbohydrate plasma volume expanders as a novel polymer platform for tumor targeting. Many synthetic polymers have already been synthesized for targeted tumor therapy, but potential advantages of these carbohydrates include inexpensive synthesis, constant availability, a good safety profile, biodegradability and the long clinical use as plasma expanders. Three polymers have been tested for cytotoxicity and cytokine activation in cell cultures and conjugated with a near-infrared fluorescent dye: hydroxyethyl starches (HES 200 kDa and HES 450 kDa) and dextran (DEX 500 kDa). Particle size and molecular weight distribution were determined by asymmetric flow field-flow fractionation (AF4). The biodistribution was investigated non-invasively in nude mice using multispectral optical imaging. The most promising polymer conjugate was characterized in human colon carcinoma xenograft bearing nude mice. A tumor specific accumulation of HES 450 was observed, which proves it's potential as carrier for passive tumor targeting.
authors.affiliation: Institute of Pharmacy, Pharmaceutical Technology and Biopharmacy, Martin-Luther-University Halle-Wittenberg, 06120 Halle, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Henrike
authors.initials: H
authors.lastname: Caysa
authors.forename: Judith
authors.initials: J
authors.lastname: Kuntsche
authors.forename: Patrick
authors.initials: P
authors.lastname: Kreideweiss
authors.forename: Anja
authors.initials: A
authors.lastname: Leimert
authors.forename: Thomas
authors.initials: T
authors.lastname: Mueller
authors.forename: Karsten
authors.initials: K
authors.lastname: Mäder
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D003911:Dextrans / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010952:Plasma Substitutes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D016207:Cytokines; D003911:Dextrans; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes