Whey Protein-Based Hydrogel Microspheres for Endovascular Embolization

Transarterial embolization (TAE) is an image-guided, minimally invasive procedure for treating various clinical conditions by delivering embolic agents to occlude diseased arteries. Conventional embolic agents focus on vessel occlusion but can cause unintended long-term inflammation and ischemia in healthy tissues. Next-generation embolic agents must exhibit biocompatibility, biodegradability, and effective drug delivery, yet some degradable microspheres degrade too quickly, leading to the potential migration of fragments into distal blood vessels causing off-target embolization. This study presents the development of whey protein hydrogel microspheres (WPHMS) made from methacrylated whey protein, which successfully withstood terminal sterilization by autoclaving. In vitro characterization revealed that sterile WPHMS are suspensible in iodine-containing contrast agents, injectable through standard catheters and microcatheters, and can be temporarily compressed by at least 12.8% without permanent deformation. Cytocompatibility was confirmed using NIH/3T3 cells, while enzymatic degradation was assessed with proteinase K. Preliminary drug loading and release studies demonstrated the potential for doxorubicin hydrochloride (Dox-HCl) as a model drug. In vivo assessments in rabbit renal models showed that WPHMS successfully occluded the renal arteries in the acute study and remained in the renal arteries for up to 3 weeks in the chronic study, with signs of early degradation. Fibrous tissue anchored the degraded residues, minimizing the risk of migration. These findings indicate that WPHMS holds significant promise as endovascular embolization agents for minimally invasive therapies.