Disulfiram-containing polymeric nanocapsules with anticancer activity for cancer treatment

Abstract

Disulfiram, a medication traditionally used to treat alcohol addiction, has gained attention as a potential cancer treatment in recent years. Disulfiram works by inhibiting the enzyme aldehyde dehydrogenase, involved in the breakdown of acetaldehyde, a by-product of alcohol metabolism. This results in the build up of acetaldehyde in the body leading to unpleasant side effects such as nausea and vomiting when alcohol is consumed while taking the drug. With cancer treatment, disulfiram has been found to have several mechanisms of action. It has been shown to inhibit cancer cell growth and metastasis and to induce apoptosis in cancer cells. Additionally, disulfiram has been found to sensitize cancer cells to other treatments, including chemotherapy and radiation therapy, by increasing their susceptibility to these treatments. Disulfiram treatment is effective against a variety of cancers, including breast cancer, prostate cancer, and glioblastoma. Overall, disulfiram holds promise as a potentially effective and inexpensive cancer treatment. Thus, researchers are exploring various delivery systems for disulfiram in cancer treatment to improve its effectiveness and reduce its side effects. Among delivery systems nanoparticles and liposomes have been used to deliver disulfiram. Our study demonstrates the efficacy of polycaprolactone-based nanocapsules for encapsulating DSF, maintaining stable size distribution (∼250 nm) and long-term stability. These nanocapsules exhibit sustained, controlled DSF release, effectively addressing the drug's instability in the bloodstream and showing promising therapeutic potential. Notably, DSF-loaded nanocapsules exhibited a twofold increase in cytotoxicity against certain tumors compared to free DSF, attributed to their extended-release profile. These findings highlight the potential of nanocapsules to improve therapeutic efficacy while reducing side effects.

Keywords: Cancer; Disulfiram; Drug delivery system; Nanocapsules; Polycaprolactone.