Porous hydroxyapatite microparticles loaded with 169Er for treatment of chronic inflammatory disease of small joints: harnessing mechanochemistry for synthesis of an advanced biomaterial

Abstract

In the present study, nanoporous hydroxyapatite microparticles (HA MPs) were synthesized using a D(+)-glucose template mediated solid state mechanochemical approach. The synthesized nanoporous HA MPs were extensively characterized and found to have a particle size distribution in the range of 1–10 µm. The nanoporous HA MPs demonstrated high sorption capacity for ¹⁶⁹Er (285 ± 8 mg g⁻¹), which in turn facilitated loading of clinically relevant doses of low specific activity ¹⁶⁹Er produced in a medium neutron flux research reactor. The sorption of ¹⁶⁹Er in nanoporous HA followed the Langmuir–Freundlich adsorption isotherm and pseudo second order kinetics. The details of the sorption mechanism were investigated using density functional theory (DFT)-based calculations. The ¹⁶⁹Er-loaded nanoporous HA ([¹⁶⁹Er]Er-HA) MPs retained their radiochemical integrity (>98%) over a period of 14 days in physiological media. As a proof of concept, [¹⁶⁹Er]Er-HA MPs were administered intra-articularly in one of the ankle joints of healthy Wistar rats. The homogeneous diffusion of the MPs formulation in the joint cavity was ascertained by SPECT/CT imaging and ex vivo biodistribution studies. Overall, the suitability of nanoporous HA MPs synthesized by a solid state route for loading low specific activity therapeutic radionuclides was established, which makes them an ideal agent for treatment of inflammatory small joint disorders and other ailments.