Preparation and evaluation of degradable imaging drug loaded embolization microspheres for hepatocellular carcinoma.

Abstract

Transarterial chemoembolization (TACE) necessitates the use of embolic agents with intrinsic radiopacity and controlled biodegradability to enhance therapeutic precision. In addressing the limitations inherent in current drug-eluting microspheres (DEMs), this study introduces the development of inherently radiopaque and biodegradable (DOX+Lipiodol) @PLGA @CaCO₃ @Alg core-shell microspheres. These microspheres were synthesized using rotating membrane emulsification and surface-induced ion crosslinking, with calcium carbonate serving multiple roles: a solid surfactant for Pickering stabilization, an acid-neutralizing agent, and an alginate shell inducer. The microspheres successfully encapsulated iodine loads, demonstrated by CT values reaching up to 8,000 HU, and contained doxorubicin at 1.53 ± 0.12 wt.%. They exhibited prolonged radiopacity for over 14 days in vivo and showed a pH-responsive drug release pattern, releasing 90% of their payload at pH 5.2 compared to 30% at pH 7.2 over 120 h. The sequential degradation process (alginate → CaCO₃ → PLGA) resulted in greater than 60% mass loss within four months, correlating with a reduction in CT attenuation. In rabbit embolization models, the microspheres achieved effective vascular occlusion and induced ischemic necrosis in ears and kidneys. CT tracking was possible without additional contrast agents, and systemic biosafety was confirmed with cell viability exceeding 90%, hemolysis below 1%, and normal hematological and histological profiles. These findings suggest that the microspheres could serve as a clinically translatable platform for image-guided TACE, integrating occlusion, therapy, and monitoring into a cohesive treatment strategy.