Abstract No. 548 Controlled Doxorubicin Release from a Distally Penetrating Polyelectrolyte Gel Embolic Material

Transarterial chemoembolization (TACE) is an important tool in interventional oncology (IO). However, TACE is limited to particle embolics or Lipiodol slurries. This study examined the feasibility of loading doxorubicin (DOX) into a polyelectrolyte gel embolic (study material), found to provide durable and deep distal penetration in preclinical and clinical studies. The study included an in vitro characterization of the loading, solidification, and drug release profile of this study material loaded with DOX. A durable, distal embolic with a sustained elution of DOX may provide advantages over current solutions for IO applications. DOX was mixed directly into the study material at 5 and 10 mg/mL. For quantitative release studies, 50 μL of DOX-loaded study material was injected into a Float-A-Lyzer dialysis device (MWCO 2 kDa) and placed into a vial containing 1 mL of normal saline. The saline was replaced at each timepoint. DOX concentration in the release media was quantified by absorbance at 485 nm and used to calculate cumulative release. During drug loading, the DOX powder readily dissolved in the study material at concentrations up to 10 mg/mL. When delivered into physiological saline, the DOX-loaded study material solidified into a microporous solid, with DOX appearing to concentrate within the pores. Rheological comparison of the solidified DOX-loaded study material to standard non-loaded study material showed no adverse effect on mechanical properties of the embolic material. In vitro release studies showed minimal bolus release and a linear, zero-order release profile over the first 36 days, followed by continued release out to 100 days (Higuchi model). A doxorubicin-loaded polyelectrolyte gel embolic provided a zero-order release profile for 5 weeks and sustained release of doxorubicin out to 100 days. The long linear release profile is desirable in drug delivery, as a constant amount of drug is delivered regardless of the concentration within the carrier. These properties are unique in the field of liquid embolics and warrant further development and testing. Future studies will examine other chemotherapeutic agents and efficacy in animal models.