Synthesis and assessment of drug-eluting microspheres for transcatheter arterial chemoembolization

• Published in: Acta biomaterialia Vol. 88; pp. 370 - 382
• Main Authors: Du, Lingran, Huang, Yugang, Zhang, Qiang, Zhou, Yi, Huang, Jianwen, Yan, Libiao, Yu, Zongjun, Qin, Aiping, Yang, Hainan, Chen, Mianrong, Liang, Lu, Bian, Biyun, Li, Xufeng, Fu, Jijun
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2019; Elsevier BV
• Subjects: Acrylic acid; Animals; Catheters; Cell Death - drug effects; Cell Proliferation - drug effects; Chemoembolization; Chemoembolization, Therapeutic; Cytotoxicity; Doxorubicin; Doxorubicin - pharmacology; Drug delivery; Drug vehicle; Elastic Modulus; Elasticity; Embolization; Hepatocellular carcinoma; Human Umbilical Vein Endothelial Cells - cytology; Human Umbilical Vein Endothelial Cells - drug effects; Humans; Injections; Ion exchange; Ion-exchange microspheres; Kidney - diagnostic imaging; Kidney - pathology; Medical instruments; Microspheres; Morphology; Particle Size; Polyhydroxyethyl methacrylate; Polyhydroxyethyl Methacrylate - chemistry; Polymerization; Rabbits; Saline Solution; Spectrophotometry, Infrared; Surface Properties; Suspension polymerization; Toxicity; Viscoelasticity; Viscosity; Water - chemistry; Doxorubicin; Drug vehicle; Ion-exchange microspheres; Chemoembolization
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2019.02.035

[Display omitted] Transcatheter arterial chemoembolization (TACE) is well known as an effective treatment for inoperable hepatocellular carcinoma (HCC). In this study, a novel embolic agent of ion-exchange poly(hydroxyethyl methacrylate-acrylic acid) microspheres (HAMs) was successfully synthesized by the inverse suspension polymerization method. Then, HAMs were assessed for their activity as an embolic agent by investigating morphology, particle size, water retention capability, elasticity and viscoelasticity, microcatheter/catheter deliverability, cytotoxicity, renal arterial embolization to rabbits and histopathological examinations. The ability of drug loading and drug eluting of HAMs was also investigated by using doxorubicin (Dox) as the model drug. HAMs showed to be feasible and effective for vascular embolization and to be as a drug vehicle for loading positively charged molecules and potential use in the clinical interventional chemoembolization therapy. A novel embolic agent of ion-exchange poly(hydroxyethyl methacrylate-acrylic acid) microspheres (HAMs) was successfully synthesized by the inverse suspension polymerization method and was used as a drug vehicle to load positively charged molecules by ion absorption. Then, a series of assessments including physicochemical properties, mechanical properties, drug-loading capability, and embolic efficacy were performed. Surface and cross-section morphology and pore size of fully hydrated HAMs were first investigated by Phenom ProX SEM, which intuitively disclosed the “honeycomb” network morphology. HAMs also showed to be feasible and effective for vascular occlusion and have potential use in clinical interventional embolization therapy.