title: MRI-visible poly(ε-caprolactone) with controlled contrast agent ratios for enhanced visualization in temporary imaging applications.
abstract: Hydrophobic macromolecular contrast agents (MMCAs) are highly desirable to provide safe and efficient magnetic resonance (MR) visibility to implantable medical devices. In this study, we report on the synthesis and evaluation of novel biodegradable poly(ε-caprolactone)-based MMCAs. Poly(α-propargyl-ε-caprolactone-co-ε-caprolactone)s containing 2, 5, and 10 mol % of propargyl groups have been prepared by ring-opening copolymerization of ε-caprolactone and the corresponding propargylated lactone. In parallel, a diazido derivative of the clinically used diethylenetriaminepentaacetic acid (DTPA)/Gd(3+) complex has been synthesized. Finally, MRI-visible poly(ε-caprolactone)s (PCLs) were obtained by the efficient click ligation of these compounds via a Cu(I)-catalyzed [3 + 2] cycloaddition. ICP-MS analyses confirmed the efficient coupling of the complex on the PCL backbone with the MRI-visible PCLs containing 1.0, 2.6, and 3.6 wt % of Gd(3+). The influence of the Gd(3+) grafting density on the T1 relaxation times and on the MRI visibility of the novel biodegradable MMCAs was evaluated. Finally, their stability and cytocompatibility were assessed with regard to their potential as innovative MRI-visible biomaterials for biomedical applications.
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR CNRS 5247, University of Montpellier 1 , University of Montpellier 2 - ENSCM , Faculty of Pharmacy, 15 Av. C. Flahault, Montpellier, 34093, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: El Habnouni
authors.forename: Benjamin
authors.initials: B
authors.lastname: Nottelet
authors.forename: Vincent
authors.initials: V
authors.lastname: Darcos
authors.forename: Barbara
authors.initials: B
authors.lastname: Porsio
authors.forename: Laurent
authors.initials: L
authors.lastname: Lemaire
authors.forename: Florence
authors.initials: F
authors.lastname: Franconi
authors.forename: Xavier
authors.initials: X
authors.lastname: Garric
authors.forename: Jean
authors.initials: J
authors.lastname: Coudane
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D049109:Cell Proliferation; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D019786:Gadolinium DTPA / Q000737:chemistry / Q000378:metabolism; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D015394:Molecular Structure; D011091:Polyesters / Q000737:chemistry / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D003287:Contrast Media; D046911:Macromolecular Substances; D011091:Polyesters; C016240:polycaprolactone; D019786:Gadolinium DTPA