Synthesis and use of hyaluronic acid-[sup.10]B polymeric chelates for neutron-capture therapy

The technology of solid-state modification of hyaluronic acid (HA) with sodium decahydroborate by deformation in Bridgman anvils was developed. The deformation was carried out at a pressure of 1 GPa and a rotation angle of 500°. The structure of the obtained complexes was studied. It was shown using Raman and IR-Fourier spectroscopy that HA and the polyborates could form a network of cyclic polymeric chelate complexes in which HA acted as a multidentate ligand. The biodistribution of the HA-based B-containing compound in organs and tissues of mice with B-16 melanoma was studied after a single intratumoral administration. The maximum B content in the tumor was observed 15 min after administration. However, it was halved after 1 h and decreased by 5 times by 3 h. The most opportune time for performing a boron-neutron-capture therapy session was 30 min after administration when the tumor B concentration was > 30µg/g and exceeded the content in surrounding tissues. The tumor/muscle and tumor/blood ratios reached 3 and 5, respectively. Use of this non-toxic compound for neutron-capture therapy was deemed promising based on preclinical studies. Keywords: hyaluronic acid, [sup.10]B, Bridgman anvils, biodistribution, B-16 melanoma, neutron-capture therapy.