The aim of this study was to prepare a solid dispersion formulation of curcumin to\nenhance its solubility, dissolution rate, and oral bioavailability. The formulation was prepared with\nD-�±-tocopheryl polyethylene glycol 1000 succinate (TPGS) and mannitol using solvent evaporation\nand freeze-drying methods, which yielded a solid dispersion composed of curcumin, TPGS,\nand mannitol at a ratio of 1:10:15 (w/w/w). The solubility and dissolution rate of the curcumin solid\ndispersion markedly improved compared with those of curcumin powder and a physical mixture of\ncurcumin, TPGS, and mannitol. About 90% of the curcumin was released from the solid dispersion\nformulation within 10 min. After administering the formulation orally to rats, higher plasma\nconcentrations of curcumin were observed, with increases in the maximum plasma concentration\n(Cmax) and area under the plasma concentration-time curve (AUC) of 86- and 65-fold, respectively,\ncompared with those of curcumin powder. The solid dispersion formulation effectively increased\nintestinal permeability and inhibited P-gp function. These effects increased the anti-proliferative\neffect of curcumin in MDA-MB-231 breast cancer cells. Moreover, 2 h incubation with curcumin\npowder, solid dispersion formulation, and its physical mixture resulted in differential cytotoxic effect\nof paclitaxel in P-gp overexpressed LLC-PK1-P-gp and MDA-MB-231 cells through the inhibition\nof P-gp-mediated paclitaxel efflux. In conclusion, compared with curcumin, a solid dispersion\nformulation of curcumin with TPGS and mannitol could be a promising option for enhancing\nthe oral bioavailability and efficacy of curcumin through increased solubility, dissolution rate,\ncell permeability, and P-gp modulation.
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