title: Evaluation of Gd-DTPA-monophytanyl and phytantriol nanoassemblies as potential MRI contrast agents.
abstract: Supramolecular self-assembling amphiphiles have been widely used in drug delivery and diagnostic imaging. In this report, we present the self-assembly of Gd (III) chelated DTPA-monophytanyl (Gd-DTPA-MP) amphiphiles incorporated within phytantriol (PT), an inverse bicontinuous cubic phase forming matrix at various compositions. The dispersed colloidal nanoassemblies were evaluated as potential MRI contrast agents at various magnetic field strengths. The homogeneous incorporation of Gd-DTPA-MP in PT was confirmed by polarized optical microscopy (POM) and synchrotron small-angle X-ray scattering (SAXS) of the bulk phases of the mixtures. The liquid crystalline nanostructures, morphology, and the size distribution of the nanoassemblies were studied by SAXS, cryogenic transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS). The dispersions with up to 2 mol % of Gd-DTPA-MP in PT retained inverse cubosomal nanoassemblies, whereas the rest of the dispersions transformed to liposomal nanoassemblies. In vitro relaxivity studies were performed on all the dispersions at 0.54, 9.40, and 11.74 T and compared to Magnevist, a commercially available contrast agent. All the dispersions showed much higher relaxivities compared to Magnevist at both low and high magnetic field strengths. Image contrast of the nanoassemblies was also found to be much better than Magnevist at the same Gd concentration at 11.74 T. Moreover, the Gd-DTPA-MP/PT dispersions showed improved relaxivities over the pure Gd-DTPA-MP dispersion at high magnetic fields. These stable colloidal nanoassemblies have high potential to be used as combined delivery matrices for diagnostics and therapeutics.
authors.affiliation: CSIRO , Manufacturing Flagship, P.O. BOX 52, North Ryde, New South Wales 1670, Australia.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Gupta
authors.forename: Liliana
authors.initials: L
authors.lastname: de Campo
authors.forename: Beenish
authors.initials: B
authors.lastname: Rehmanjan
authors.forename: Scott A
authors.initials: SA
authors.lastname: Willis
authors.forename: Lynne J
authors.initials: LJ
authors.lastname: Waddington
authors.forename: Tim
authors.initials: T
authors.lastname: Stait-Gardner
authors.forename: Nigel
authors.initials: N
authors.lastname: Kirby
authors.forename: William S
authors.initials: WS
authors.lastname: Price
authors.forename: Minoo J
authors.initials: MJ
authors.lastname: Moghaddam
mesh_terms: D003287:Contrast Media; D020285:Cryoelectron Microscopy; D005233:Fatty Alcohols / Q000737:chemistry*; D019786:Gadolinium DTPA / Q000008:administration & dosage* / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D046529:Microscopy, Electron, Transmission; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction
chemical_list: D003287:Contrast Media; D005233:Fatty Alcohols; C508873:3,7,11,15-tetramethyl-1,2,3-hexadecanetriol; D019786:Gadolinium DTPA