Enhanced cytotoxic, antioxidant and anti-inflammatory activities of curcumin diethyl disuccinate using chitosan-tripolyphosphate nanoparticles

Abstract Curcumin diethyl disuccinate (CDD) is an ester prodrug of curcumin previously shown to have better stability and cytotoxicity against cancer cell lines compared to curcumin. However, the lipophilic character of CDD may hinder its further development for preclinical and clinical studies. In this study, CDD-loaded chitosan-tripolyphosphate nanoparticles (CDD–CS–TPP-NPs) were optimized and further tested for their biological activities. The CDD–CS–TPP-NPs were fabricated by oil-in-water emulsification and ionotropic gelation. The effect of the CS, Tween ® 80 and CDD concentrations on the characteristics of the CDD–CS–TPP-NPs were investigated to optimize the formulation using response surface methodology. The formulation with 0.15% (w/v) CS, 1% (w/v) Tween ® 80 and 1.5 mg/mL CDD was found to be optimal and that it should be stored at 4 °C. The release rate of CDD from the optimized CDD–CS–TPP-NPs depended on the pH of the simulated fluids (pH 1.2 > pH 4.5 > pH 6.8 > pH 7.4). Compared to free CDD, the optimized CDD–CS–TPP-NPs showed better biological activities, including a mucoadhesive property, cellular uptake and cytotoxicity against Caco-2 cells, and antioxidant and anti-inflammatory effects in lipopolysaccharide-activated RAW 264.7 cells.