Novel oral delivery system using modified inulin for enhanced liver cancer therapy.

Abstract

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths worldwide. Although advanced oral anticancer drugs, such as sorafenib and lenvatinib, are available for treating HCC, their effectiveness is limited by significant side effects and the requirement for optimal liver function, restricting their broader use. Furthermore, these drugs cannot be used in combination, leading to suboptimal treatment outcomes. This study introduces a novel therapeutic approach by repurposing two existing drugs, niclosamide and disulfiram, as a combination therapy to treat HCC. Despite their known anticancer properties, these drugs face challenges such as high lipophilicity and a significant first-pass effect, resulting in low bioavailability. To overcome this limitation, we used chemically modified inulin fibers as oral carriers to enhance drug absorption and protect the drugs from the acidic gastric environment. We compared the efficacy of this system across two HCC cell lines-HepG2 (from a Caucasian patient) and Huh6 (from an Asian patient)-to explore how genetic and ethnic variations impact sensitivity to the proposed therapeutic approach. Our findings indicate that the proposed inulin oral delivery approach improves drug efficacy both in vitro and in vivo. Moreover, our comparative study underscores the importance of considering ethnic and genetic diversity in designing effective cancer therapies. Overall, the proposed oral delivery system can potentially reduce the need for invasive procedures, lower infection risks, and minimize patient discomfort by avoiding the need for intravenous administration, while improving treatment outcomes.