Disulfiram-loaded nanoemulsions for enhanced anticancer efficacy in peritoneal carcinomatosis: Design, optimization, in vitro and in vivo evaluation

Disulfiram (DSF), an FDA-approved anti-alcoholism drug, has demonstrated potent anticancer activity against peritoneal carcinomatosis. However, its therapeutic potential is severely hampered by poor aqueous solubility and instability. Nanoemulsion system provides a promising platform to overcome these challenges. Herein, this study developed and optimized a DSF-loaded nanoemulsions (DSF-NE) to enhance the therapeutic efficacy of DSF in peritoneal carcinomatosis. The optimized DSF-NE exhibited several formulation advantages, including a small particle size (∼84 nm), narrow size distribution (∼0.1), high encapsulation efficiency (>90 %) and sustained-release behavior. Subsequently, cytotoxicity assays against MGC-803, SKOV-3 and Caco-2 cells revealed that DSF-NE significantly enhanced cytotoxic effects compared to DSF, with IC 50 values reduced by 74 %, 62 % and 56 %, respectively. Consistently, DSF-NE achieved a tumor inhibition rate 108.57 % higher than that of DSF in a murine peritoneal carcinomatosis model. The main mechanism involves enhanced cellular uptake of DSF-NE, which promotes ROS generation and subsequently triggers apoptosis. Collectively, these findings highlight DSF-NE as a nanoformulation strategy that not only improves the therapeutic performance of DSF in peritoneal carcinomatosis but also offers broader implications in the development of effective delivery systems for poorly soluble and unstable drugs.