Curcumin micronization by supercritical fluid: In vitro and in vivo biological relevance

Curcumin, a polyphenol extracted from the rhizome of Curcuma longa L. (Zingiberaceae), is shown to have antioxidant, anti-inflammatory, neuroprotective, anxiolytic, and antidepressant properties in both preclinical and clinical studies. However, its low bioavailability is a limitation for its potential adoption as a therapeutic agent. The process of micronization can overcome this barrier by reducing the particle size and increasing the dissolution rate, potentially improving the bioavailability of the compounds of interest. In this study, we compared the in vitro antioxidant effects of curcumin (CUR) and micronized curcumin (MC) and studied their effects on behavioral and neurochemical parameters in zebrafish submitted to unpredictable chronic stress (UCS). MC was processed by the solution enhanced dispersion by supercritical fluids (SEDS) technique obtaining a particle average size of 2.29 µm (8 MPa and 35 °C), which means a reduction of 5.4 times. MC (1 g/L) presented higher antioxidant activity in vitro as compared to CUR, as measured by iron-reducing antioxidant power (FRAP), 1,1-diphenyl-2–2-picyryl-hydrazyl radical removal (DPPH), and deoxyribose tests. UCS increased total distance traveled in the social interaction test (SI), while decreased crossings, time, and entries to the top area in the novel tank test (NTT). No effects of UCS were observed in the open tank test (OTT). The behavioral effects induced by UCS were not blocked by any curcumin preparation. UCS also decreased non-protein thiols (NPSH) levels, while increased glutathione reductase (GR) activity and thiobarbituric acid reactive substances (TBARS) levels on zebrafish brain. MC presented superior antioxidant properties than CUR in vivo, blocking the stress-induced neurochemical effects. Although this study did not measure the concentration of curcumin on the zebrafish brain, our results suggest that micronization increases the bioavailability of curcumin, potentiating its antioxidant activity both in vitro and in vivo. Our study also demonstrates that counteracting the oxidative imbalance induced by UCS is not sufficient to block its behavioral effects.