MEAN-Eluting Microspheres for Catheter-Directed Delivery to Liver Tumors

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and third most common cause of cancer-related death worldwide. Curative surgical interventions are rarely an option. Patients are commonly treated with palliative loco-regional approaches; however, with these palliative approaches, improvements in patient survival remain modest. Recently, catheter-directed delivery of drugs to HCC has been accomplished using drug-eluting microspheres. The drug amonafide has demonstrated potent efficacy for the treatment of a broad range of solid tumors but clinical application has been limited due to severe toxicities. These toxicities have been mitigated with the recently developed metabolically stable drug 6-methoxyethylamino numonafide (MEAN). We propose the development of MEAN-eluting magnetic alginate microspheres to permit selective transcatheter delivery thus increasing therapeutic efficacy of this drug for the treatment of HCC and further reducing toxicity. Our multidisciplinary studies will address two Specific Aims. In Aim 1, we will determine the relationship between our microfluidic microsphere synthesis protocols and resulting MEAN loading and release kinetics. For Aim 2, using HCC rat models, we will compare therapeutic outcomes following intra-hepatic transcatheter administration of MEAN-eluting microspheres and IV MEAN administration procedures in rat HCC