title: Surface modification of PLGA nanospheres with Gd-DTPA and Gd-DOTA for high-relaxivity MRI contrast agents.
abstract: The preparation of particulate contrast agents for magnetic resonance imaging (MRI) based on biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanocarriers is reported. By spacer-aided covalent surface-grafting of the prominent chelating ligands diethylenetriaminepentaacetic acid (DTPA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), respectively, up to 236 μg gadolinium per mg PLGA can be immobilized in a stable manner. Due to the localisation at the particle surface, water protons may effectively interact with the gadolinium chelates and the modified particles exhibit high proton relaxivities as confirmed by T1 relaxivities of up to 17.5 mm(-1)s(-1) (25 °C, 1.41 T) in case of Gd-DOTA-functionalized carriers and also supported by NMRD profiles. The obtained values compare favorably with marketed low-molecular weight contrast agents and thus suggest suitability for in vivo use.
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria.
authors.forename: Gerda
authors.initials: G
authors.lastname: Ratzinger
authors.forename: Prashant
authors.initials: P
authors.lastname: Agrawal
authors.forename: Wilfried
authors.initials: W
authors.lastname: Körner
authors.forename: Julia
authors.initials: J
authors.lastname: Lonkai
authors.forename: Honorius M H F
authors.initials: HM
authors.lastname: Sanders
authors.forename: Enzo
authors.initials: E
authors.lastname: Terreno
authors.forename: Michael
authors.initials: M
authors.lastname: Wirth
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Strijkers
authors.forename: Klaas
authors.initials: K
authors.lastname: Nicolay
authors.forename: Franz
authors.initials: F
authors.lastname: Gabor
mesh_terms: D003287:Contrast Media; D019786:Gadolinium DTPA / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D054118:Nanospheres / Q000737:chemistry* / Q000648:ultrastructure; D009942:Organometallic Compounds / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D019786:Gadolinium DTPA