title: Preparation and initial characterization of biodegradable particles containing gadolinium-DTPA contrast agent for enhanced MRI.
abstract: Accurate imaging of atherosclerosis is a growing necessity for timely treatment of the disease. Magnetic resonance imaging (MRI) is a promising technique for plaque imaging. The goal of this study was to create polymeric particles of a small size with high loading of diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) and demonstrate their usefulness for MRI. A water-in-oil-in-oil double emulsion solvent evaporation technique was used to encapsulate the MRI agent in a poly(lactide-co-glycolide) (PLGA) or polylactide-poly(ethylene glycol) (PLA-PEG) particle for the purpose of concentrating the agent at an imaging site. PLGA particles with two separate average sizes of 1.83 microm and 920 nm, and PLA-PEG particles with a mean diameter of 952 nm were created. Loading of up to 30 wt % Gd-DTPA was achieved, and in vitro release occurred over 5 h. PLGA particles had highly negative zeta potentials, whereas the particles incorporating PEG had zeta potentials closer to neutral. Cytotoxicity of the particles on human umbilical vein endothelial cells (HUVEC) was shown to be minimal. The ability of the polymeric contrast agent formulation to create contrast was similar to that of Gd-DTPA alone. These results demonstrate the possible utility of the contrast agent-loaded polymeric particles for plaque detection with MRI.
authors.affiliation: Department of Biomedical Engineering, University of Texas, Austin, TX 78712, USA.
authors.forename: Amber L
authors.initials: AL
authors.lastname: Doiron
authors.forename: Kevin
authors.initials: K
authors.lastname: Chu
authors.forename: Adeel
authors.initials: A
authors.lastname: Ali
authors.forename: Lisa
authors.initials: L
authors.lastname: Brannon-Peppas
mesh_terms: D050197:Atherosclerosis / Q000175:diagnosis*; D002460:Cell Line; D003287:Contrast Media / Q000633:toxicity; D042783:Endothelial Cells / Q000187:drug effects; D019786:Gadolinium DTPA; D006801:Humans; D019344:Lactic Acid / Q000138:chemical synthesis*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011100:Polyglycolic Acid / Q000138:chemical synthesis*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D003287:Contrast Media; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D019786:Gadolinium DTPA
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