Nanoemulsions loaded with 5-fluorouracil and curcumin as a strategy for enhancing anticancer activity in FaDu cells for treating oral cancer.

Abstract

e18035 Background: 5-fluorouracil (5-FU), a chemotherapeutic agent, and curcumin (Cur), a natural antioxidant, offer a broad pharmacological window for treating oral cancer; nevertheless, both medicines have low bioavailability. This research study plans to develop a nanoemulsion (NE) formulation by combining 5-FU with Cur to boost anticancer activity against oral squamous cell carcinoma (OSCC) cells, FaDu (hypopharyngeal tumor). Methods: 5-FU/Cur-NE was formulated through homogenization, applying high-energy ultrasonication techniques. Then it was characterized by different in vitro assays to evaluate the release and treatment efficiency in FaDu cells. To monitor the anticancer activity of 5-FU/Cur -NE, including inhibition rate, apoptotic changes in plasma membrane, and protein densitometry, MTT assay, Annexin V assay using flow cytometry, and a western blot analysis of the apoptotic markers (Bcl-2, Bax, and active caspase 3) were performed. Results: 5-FU/Cur -NE was successfully formulated and showed a mean value of the particle size 148.3 nm, PDI (0.154), surface charge (- 25.5mV), and in vitro release of 5-FU/Cur -NEs was monitored over the course of two days at pH 7.4 along with acceptable stability data. According to the dose-dependent cytotoxicity analysis, 5-FU/Cur -NE had a lower IC 50 value (4.3±4 9) at 24 hours than 5-FU (27.6± 9.6) and was significantly more effective at higher doses. The Annexin V assay further demonstrated that 5-FU/Cur -NE treatment induces apoptosis of FaDu cells in a dose-dependent manner. The treated cells showed ≥70% apoptosis (early and late) induction as compared to untreated cells. Along with, active/pro-caspase3 was found to have a substantial change in protein fold at higher concentrations, whereas Bax expression was increased at lower doses compared to the control. Meanwhile, as 5-FU/Cur -NE concentration rises, Bcl-2 was gradually down regulated (80% reduced expression at 100nm), indicating effective anti-cancer properties. Conclusions: The 5-FU/Cur -NE showed promising functionality compared to the systemic chemotherapeutic regimen. It exhibited enhanced cytotoxicity at a lower IC 50 value and was attributed to increased apoptosis of oral cancer FaDu cells. Therefore, in the near future, the effective anticancer potency of 5-FU/Cur -NE can be considered formidable system to deliver drugs for improved treatment options in oral cancer patients.