Co-delivery of 5-Fluorouracil and Curcumin Nanohybrid Formulations for Improved Chemotherapy Against Oral Squamous Cell Carcinoma

Abstract

Purpose The chemotherapeutics agent, 5-fluorouracil (5-FU), and curcumin (Cur), a natural antioxidant, has a wide pharmacological window to treat oral carcinoma; however, both drugs have limited bioavailability. This research study designs to develop a nanoemulsions (NEs) formulation by combining 5-FU and Cur to improve anticancer activity against oral cavity squamous cell carcinoma (OSCC) cells from the diversified origin for in vitro analysis, SCC090 (human tongue) and SCC152 (human hypo-pharynx). Methodology NEs formulated through homogenization, applying high-energy ultrasonication technique. The prepared 5-FUNE/Cur-NE/5-FU-Cur-NE were characterized and optimized by different in vitro assays to evaluate release system and treatment of OSCC cells to monitor cellular acceptability, such as in vitro anticancer activity by MTT assay, cell uptake studies and protein expression associated apoptotic study. Results 5-FUNE/Cur-NE/5-FU-Cur-NE successfully formulated and show mean-value of the particle size (150-200 nm), surface charge (-25.70 to-37.91 mV), and PDI (0.194). In vitro release of 5-FUNE/Cur-NE/5-FU-Cur-NEs was monitored over a course of 04 days, where acidic pH shows higher release as compared to alkaline pH, along with acceptable stability data. Cytotoxicity study has shown higher-dose-dependent anticancer effect with a reduced IC50 value of NEs as compared to BLNE. Cellular uptake study of 5-FUNE/Cur-NE/5-FU-Cur-NEs upgraded many folds, comparatively BLNE and show potential cell arrest. Additionally, the cell protein (Blc2, Bax, P53, and P21) expression was revised and raised cell apoptosis. Conclusion The combinational loaded, 5-FU and Cur in nanoformulation system have proven their potency to deliver improved anticancer activity, against oral cancer. Keywords 5-Fluorouracil Á Curcumin Á Oral cancer Á Nanoparticles Á Drug Delivery Saurabh Srivastava and Shadab Mohammad are equally contributed for the manuscript.

Drug Delivery (Nano)Platforms for Oral and Dental Applications: Tissue Regeneration, Infection Control, and Cancer Management

“…Nanoemulsions provide targeted delivery and sustained-release that are of importance in promoting anti-cancer activity of both curcumin and 5-fluorouracil. [288] These studies are in agreement with the capability of nanoparticles as synergistic factors in anti-cancer therapy. Table 2 summarizes the recent progress in using nanoaprticles for therapy against oral cancer.…”

Comparative and Mechanistic Study on the Anticancer Activity of Quinacrine-Based Silver and Gold Hybrid Nanoparticles in Head and Neck Cancer

“…37−39 It is now a wellaccepted fact that the nanoparticles were absorbed at the surface of the cancer cells and eventually got internalized into the cell and through various mechanisms caused cell death. 39 But due to lack of targeted delivery, normal cells are affected too. Hybrid nanoparticles have proven to be advantageous over other strategies due to their targeted and controlled delivery against cancers.…”

“…Although recent studies have reported the advancement of combination therapy to eradicate oral cancer, the morbidity and mortality rates are not changing. − It is now a well-accepted fact that the nanoparticles were absorbed at the surface of the cancer cells and eventually got internalized into the cell and through various mechanisms caused cell death . But due to lack of targeted delivery, normal cells are affected too.…”

Evidence mapping and quality assessment of systematic reviews on therapeutic interventions for oral cancer

“…Thus, nowadays, it is likely that there are other options for chemotherapy. For example, 5-fluoro-uracil, cisplatin, carboplatin, paclitaxel and docetaxel are among the chemotherapy drugs most often used for oral and oropharyngeal cancers; these may be used alone or combined with other drugs 42,43…”