title: Block-copolymer of polyethylene glycol and polylysine as a carrier of organic iodine: design of long-circulating particulate contrast medium for X-ray computed tomography.
abstract: In order to obtain small, polymer-stabilized particulate carriers for organic iodine to serve as a contrast agent for X-ray computed tomography (CT) an attempt was made to design a carrier based on polymeric micelles. Here we describe the synthesis of an iodine-containing amphiphilic block-copolymer which can micellize in aqueous solutions. The two blocks of the copolymer consisted of methoxypoly(ethyleneglycol) and poly[epsilon,N-(triiodobenzoyl)-L-lysine]. Upon dispersion in water, the block copolymer formed particles with average diameter 80 nm and iodine content up to 44.7%. The particles start to dissociate to the individual polymeric chains in the concentration range of 0.05-0.5 microM in water at 23 degrees C. Upon intravenous injection at 250 mg of iodine/kg (570 mg of the agent/kg) in rabbits the medium demonstrated exceptional 24 hr half-life in the blood substantiating corona/core structure of the particles with PEG chains protecting the iodine-containing core. The possible use of these particulates as contrast medium for X-ray computed tomography is discussed.
authors.affiliation: Center for Imaging and Pharmaceutical Research, Massachusetts General Hospital-East, Charlestown 02129.
authors.forename: V S
authors.initials: VS
authors.lastname: Trubetskoy
authors.forename: G S
authors.initials: GS
authors.lastname: Gazelle
authors.forename: G L
authors.initials: GL
authors.lastname: Wolf
authors.forename: V P
authors.initials: VP
authors.lastname: Torchilin
mesh_terms: D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media / Q000138:chemical synthesis*; D004337:Drug Carriers; D015195:Drug Design; D007455:Iodine / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D011107:Polylysine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis*; D014057:Tomography, X-Ray Computed; D014283:Triiodobenzoic Acids / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D003287:Contrast Media; D004337:Drug Carriers; D011108:Polymers; D014283:Triiodobenzoic Acids; C107536:methoxypoly(ethyleneglycol)-poly(epsilon-N-(2,4,6-triiodobenzoyl)lysine) block copolymer; D011107:Polylysine; D011092:Polyethylene Glycols; D007455:Iodine