The inhibitory effect of disulfiram encapsulated PLGA NPs on tumor growth: Different administration routes

• A new delivery system for delivery of disulfiram into breast cancer cells is proposed.
• The encapsulated disulfiram shows higher activity in apoptosis induction compared to free drug.
• The encapsulated disulfiram shows significant cytotoxicity against breast cancer cells both in vitro and in vivo.
• Different administration routes including intra-venous, intra-tumoral and intra-peritoneal are investigated.
• The intravenous route is more efficient in suppressing tumor growth compared to other routes of administration.

The strong anticancer activity of disulfiram is hindered by its rapid degradation in blood system. A novel folate-receptor-targeted poly (lactide-co-glycolide) (PLGA)-polyethylene glycol (PEG) nanoparticle (NP) is developed for encapsulation and delivery of disulfiram into breast cancer tumor using passive (EPR effect) and active (folate receptor) targeting. The anticancer activity of disulfiram and its effect on caspase-3 activity and cell cycle are studied. The administration of encapsulated PLGA NPs using intra-peritoneal, intravenous and intra-tumor routes is investigated using animal model. Disulfiram shows strong cytotoxicity against MCF7 cell line. The activity of caspase-3 inhibited with disulfiram via dose dependent manner while the drug causes cell cycle arrest in G0/G1 and S phase time-dependently. The encapsulated disulfiram shows higher activity in apoptosis induction as compared to free drug. In nontoxic dose of encapsulated disulfiram, the highest and lowest efficacy of NPs in tumor growth inhibition is observed for intravenous injection and intraperitoneal injection. It is suggested that administration of disulfiram by targeted PLGA nanoparticles using intravenous injection would present an alternative therapeutic approach for solid tumor treatment.

Figure optionsDownload as PowerPoint slide