Development of Resorbable Phosphate-Based Glass Microspheres as MRI Contrast Media Agents

In this research, resorbable phosphate-based glass (PBG) compositions were developed using varying modifier oxides including iron (Fe₂O₃), copper (CuO), and manganese (MnO₂), and then processed via a rapid single-stage flame spheroidisation process to manufacture dense (i.e., solid) and highly porous microspheres. Solid (63-200 µm) and porous (100-200 µm) microspheres were produced and characterised via SEM, XRD, and EDX to investigate their surface topography, structural properties, and elemental distribution. Complementary NMR investigations revealed the formation of Q², Q¹, and Q⁰ phosphate species within the porous and solid microspheres, and degradation studies performed to evaluate mass loss, particle size, and pH changes over 28 days showed no significant differences among the microspheres (63-71 µm) investigated. The microspheres produced were then investigated using clinical (1.5 T) and preclinical (7 T) MRI systems to determine the R₁ and R₂ relaxation rates. Among the compositions investigated, manganese-based porous and solid microspheres revealed enhanced levels of R₂ (9.7-10.5 s^-1 for 1.5 T; 17.1-18.9 s^-1 for 7 T) and R₁ (3.4-3.9 s^-1 for 1.5 T; 2.2-2.3 s^-1 for 7 T) when compared to the copper and iron-based microsphere samples. This was suggested to be due to paramagnetic ions present in the Mn-based microspheres. It is also suggested that the porosity in the resorbable PBG porous microspheres could be further explored for loading with drugs or other biologics. This would further advance these materials as MRI theranostic agents and generate new opportunities for MRI contrast-enhancement oral-delivery applications.