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The aim of the study was to devise a novel Fluvastatin (FT) based curcumin (CR) nanostructured lipid carrier (NLC) loaded into an in situ gelling system (ISG) for localized and prolonged chemotherapy in the treatment of aggressive tongue carcinoma. FT-CR NLC was prepared using the solvent evaporation method, characterized, and optimized. FT-CR NLC was loaded in a Poloxamer 407 and polyvinyl alcohol-based ISG, further characterized and evaluated. The percentage of cellular viability and caspase-3 enzyme levels were evaluated for the optimized FT-CRNLC, and loaded ISG formulations were applied to HCS-3 cancer cell lines. Stability studies were performed. The optimized FT-CR NLC was spherical with an indicated particle size of 107 ± 4.5 nm, a polydispersity index of 0.38 ± 0.6, surface charge of -31.1 ± 1.8 mV, and entrapment efficiency of 98.4% ± 0.81%. The optimized ISG had an optimum sol-gel transition temperature. The FT IC50 was decreased by half for FT-CR NLC–loaded ISG in comparison to plain FT and FT-CR NLC. The studies indicated that CR’s synergistic anti-oxidant effect in the FT NLC formulation led to a higher inhibition against HCS-3 cancer cell lines. FT-CR NLC–loaded ISG had a prolonged release that can be significant in localized therapy as an alternative to surgery, especially in the treatment of aggressive tongue squamous cell carcinoma.
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