In vitro evaluation of sunitinib loaded bioresorbable microspheres for potential application in arterial...

Drug-loadable bioresorbable microspheres (BRMS) are designed for treating hypervascular tumors through chemoembolization, thereby reducing systemic side effects via controllable local delivery. The present study investigated the degradation and loading capability of bioresorbable microspheres with an anti-angiogenic agent, sunitinib, and then evaluated the release profiles in different media (PBS, 10μg/mL and 4mg/mL lysozyme solutions), and tested catheter deliverability as well as potential antiangiogenic effects of the loaded microspheres. The dry weight of the BRMS showed a consistent decrease over the period of incubation in a 10μg/mL lysozyme solution with 61.3% mass remaining on day 21. Sunitinib was loaded efficiently onto the microspheres, with smaller sizes exhibiting a slightly faster loading and release rate. At 2h, the loading percentages were 99.28%, 97.95%, and 94.39% for 100-300, 300-500, and 500-700μm microspheres, respectively. At 8h, the percentage of drug released were 78.4±5.8%, 71.7±0.3%, and 67.0±2.9% for 100-300, 300-500, and 500-700μm microspheres under static medium conditions, respectively. Under replacing-medium conditions, the presence of 10μg/mL lysozyme slightly delayed the drug release while 4mg/mL lysozyme significantly facilitated the drug release from the microspheres as compared with PBS solution. Confocal imaging revealed an even distribution of sunitinib throughout the microspheres. Drug loaded microspheres were delivered through microcatheters smoothly without any clogging. Sunitinib retained its efficacy at reducing the viability of human endothelial cells after elution from the microspheres. Thus, these bioresorbable microspheres are promising for arterial chemoembolization.