Nanoassemblies of Gd-DTPA-monooleyl and glycerol monooleate amphiphiles as potential MRI contrast agents

Abstract

Self-assembly of lipid-based amphiphiles into various supramolecular nanostructured particles has been used in creating novel nanomaterials with diverse applications in drug delivery and diagnostic imaging. Here we report on Gd(iii) chelated DTPA amphiphiles with an oleyl chain (Gd-DTPA-MO) incorporated within the self-assembly matrix of glycerol monooleate (GMO), an inverse cubic phase forming system, at varying compositions. The dispersed colloidal nanoassemblies were explored for their potential as magnetic resonance imaging (MRI) contrast agents. We investigated the homogeneity of the mixed amphiphiles in bulk phases by differential scanning calorimetry (DSC) and their lyotropic phase behaviour by synchrotron small angle X-ray scattering (SAXS). The liquid crystalline nanostructures, morphology and the size distribution of the nanoassemblies were studied by synchrotron SAXS, cryogenic transmission electron microscopy (cryo-TEM) and dynamic light scattering (DLS). SAXS and cryo-TEM results revealed the formation of inverse cubosomes in dispersions with ≤1 mol% of Gd-DTPA-MO, and liposomal and rod-shaped micellar aggregates with >1 mol%. The stability of cubosomal nanoassemblies was assessed in the presence of fetal bovine serum, showing minimal effect on their nanostructures. In vitro relaxivity studies were performed at four different magnetic field strengths (0.54, 7.05, 9.40 and 11.74 T). All the colloidal dispersions displayed enhanced longitudinal relaxivities per Gd over Magnevist, a commercially available contrast agent, at both low and high magnetic field strengths. In addition, cubosomes with 3D-periodic interior nanostructures, extensive water channels and high interfacial surface area, showed promise as high field contrast agents. These stable colloidal particles also have potential to be used as combined delivery matrices for diagnostics and therapeutics (theranostics). Show more