title: A novel formulation for superparamagnetic iron oxide (SPIO) particles enhancing MR lymphography: comparison of physicochemical properties and the in vivo behaviour.
abstract: The major aim of this study was to prove or disprove the theories concerning the correlation between physicochemical properties of superparamagnetic iron oxide (SPIO) particles and their accumulation in the lymph nodes. New SPIO particles were produced using starch as stabilising polymer shell. The synthesis was done in a two-step procedure using conventional wet-chemical precipitation technique and subsequent coating of the iron oxide cores. The particles were physicochemically characterised and their lymphotrophy studied in rats using well described lymphotropic dextran-coated SPIO particles as reference. Despite the short blood half-lives of approximately 13 min and the relatively large sizes (approximately 60-90 nm), the starch SPIO particles proved at least as efficient in lymph node accumulation as the small 25 nm dextran SPIO particles having a half-life of 90 min. The currently accepted theories concerning the connection between particle properties and their uptake into lymph nodes are not generally valid, or have at least to be limited for dextran-coated SPIO particles. Lymph node targeting could be achieved despite the present theories consider small size (<30 nm) and long circulation times in the blood as prerequisites. Histological examination showed, that SPIO particles could only be found in lymph node areas where macrophages could be marked which enclosed the particles. Localisation in marginal areas of the lymph nodes indicates endothelial transcytosis as the major accumulation pathway.
authors.affiliation: Department of Pharmaceutical Technology, The Free University of Berlin, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Lind
authors.forename: Mayk
authors.initials: M
authors.lastname: Kresse
authors.forename: Nils P
authors.initials: NP
authors.lastname: Debus
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Müller
mesh_terms: D000818:Animals; D002627:Chemistry, Physical / Q000379:methods; D003287:Contrast Media / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003911:Dextrans / Q000378:metabolism; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005295:Ferrocyanides / Q000494:pharmacology; D052203:Ferrosoferric Oxide; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007501:Iron / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017078:Laser-Doppler Flowmetry / Q000295:instrumentation; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism*; D008220:Lymphography / Q000379:methods; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010087:Oxides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013213:Starch / Q000378:metabolism; D013499:Surface Properties / Q000187:drug effects; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D003911:Dextrans; D005295:Ferrocyanides; D010087:Oxides; D013213:Starch; D007501:Iron; C000170:ferric ferrocyanide; D052203:Ferrosoferric Oxide