In Vitro Drug Loading, Releasing Profiles, and In Vivo Embolic Efficacy and Safety Evaluation of a Novel Drug-Eluting Microsphere (CalliSpheres).

Abstract

Background: To investigate morphology, physical property, loadability, stability, and release profiles of a novel drug-eluting microsphere, CalliSpheres, in vitro and to explore its embolic efficacy and safety in vivo. Materials and Methods: CalliSpheres (50-150 μm, 100-300 μm, and 300-500 μm) and doxorubicin in different amounts (20, 40, 80, and 100 mg) and concentrations (5 and 10 mg/mL) were prepared for experiments. Dynamic light scattering and an Agilent 1260 high-performance liquid chromatography system were used to quantify bead diameters and the efficiency of drug loading and release, respectively. Twelve New Zealand rabbits were treated with catheter-aided hepatic embolization using CalliSpheres. Results: CalliSpheres displayed a red color after loading with doxorubicin, and the mean diameters decreased by 20.7-25.8%. Almost 100% of the drug was incorporated with CalliSpheres in different sizes immersed with doxorubicin 20 mg, while loading efficiency ranged from 75.8% to 100.0% with doxorubicin at 40, 80, and 100 mg dependent on CalliSpheres sizes (smaller sizes, higher loading efficiency). Elevated loading efficiency was observed at higher concentration of doxorubicin solutions. Regarding release profiles, doxorubicin was released from CalliSpheres quickly at the very beginning, and doxorubicin release percentage was increased in the 50-150 μm group (39.2% ± 1.2%) compared with the 100-300 μm group (31.3% ± 1.3%) and 300-500 μm group (31.7% ± 2.5%). Digital subtraction angiography, computed tomography, and histopathologic emanation results proved in vivo safety and embolic efficacy of CalliSpheres. Conclusions: CalliSpheres present with good physical characteristics and satisfactory loading and releasing profiles in vitro and are well tolerated and efficient in embolization in vivo.