Holmium-loaded poly(L-lactic acid) microspheres: in vitro degradation study

The clinical application of holmium-loaded poly(L-lactic acid) (PLLA) microspheres for the radionuclide treatment of liver malignancies requires in depth understanding of the degradation characteristics of the microspheres. To this end, an in-vitro degradation study was conducted. PLLA-microspheres with and without HoAcAc loading, and before and after neutron or gamma irradiation, were incubated in a phosphate buffer at 37 degrees C for 12 months. In contrast with the other microsphere formulations, only the neutron-irradiated Ho-PLLA-MS disintegrated. At the end of the experiment (52 weeks) highly crystalline fragments, as evidenced from Differential Scanning Calorimetry, were present. Infrared spectroscopy showed that these fragments consisted of holmium lactate. In conclusion, this study demonstrates that the degradation of neutron-irradiated Ho-PLLA-MS was substantially accelerated by the HoAcAc incorporation and subsequent neutron irradiation. The degradation of these microspheres in aqueous solution resulted in the formation of insoluble holmium lactate microcrystals without release of Ho3+.