Abstract: Curcumin (Cur) nanoparticles were prepared by subcritical water (SBCW) method and its membrane permeability was evaluated. The processing conditions for the preparation of curcumin nanoparticles were investigated in terms of its particle size distribution, polydispersity index (PDI) and zeta potential, and the prepared nanoparticles were characterized and evaluated for in vitro membrane permeability. The results showed that nanoparticles with a diameter of 166 nm and a drug loading of 70.2% were obtained under the conditions: SBCW temperature 120 ℃, receiving solvent temperature 0 ℃, subcritical water/receiving solution ratio 1:3 (V/V), 0.04 g/100 mL lactose as stabilizing agent, and 30% (V/V) ethanol as entrainer. Fourier transform infrared (FTIR) spectroscopy showed no structural changes in Cur. Scanning electron microscopy (SEM) showed that Cur nanoparticles were uniformly spherical in shape. Differential scanning calorimetry (DSC) analysis showed a decrease in the crystallinity of the nanoparticles. Cur nanoparticles exhibited excellent membrane permeability in vitro, and the permeation rate in the first two hours was 25 folds higher than that of free Cur. Furthermore, Cur nanoparticles exhibited good transmembrane capacity in rabbits and significantly enhanced the bioavailability of Cur. The preparation of Cur nanoparticles using subcritical water method has the advantages of high drug loading, good membrane permeability, no need for carriers, simple process, and green environmental protection.

Key words: curcumin; subcritical water; preparation; nanoparticles; membrane permeability