Integration of cocrystal and nanocrystal techniques to ameliorate solubility, topical antioxidant activity and cytotoxicity of curcumin

Abstract Curcumin (CUM), a promising nutraceutical, exhibits diverse pharmacological activities such as antioxidant, anti-inflammatory, antitumor and anti-hyperglycemic, but the clinical applications of CUM is restricted by virtue of its scarce aqueous solubility, poor stability and, low oral and topical absorption. In this work a nano-cocrystal strategy, integrating the benefits of cocrystallization and nanocrystal techniques, has been proposed to obtain superior characters of CUM. A cocrystal of CUM was successfully synthesized with ascorbic acid by solvent evaporation and then transformed into nano-cocrystal (NCC) by a top down homogenization technique using poloxamer 188 as stabilizer. NCC delineated by SEM and Zetasizer appeared to be round-shaped particles with mean particle size of 200 ± 30nm. Further characterization was undertaken using PXRD, DSC and FTIR spectroscopy. NCC presented 16 and 10 fold enhanced solubility and dissolution of CUM in distilled water in comparison to pure CUM. From the In-vitro antioxidant and cytotoxicity studies, it was suggested that NCC displayed the highest percentage inhibition (99.154 ± 0.58%) with IC50 value of 1.4 ± 0.180µg/ml and also led to a reduction of viability of MCF-7 breast cancer cells. On formulating topical gel, NCC was stable for six months at 4 ± 2°C and 30 ± 2°C /65 ± 5% RH. In-vitro release studies of NCC gel by modified Franz diffusion cell demonstrated a 2.4fold cumulative release of CUM compared to pure CUM gel. Release data was best fitted to Hixon-Crowell kinetic model with n value showing non Fickian release. Hence, the higher solubility, greater stability and release of NCC make it a promising topical gel formulation.