Modified curcumin with hyaluronic acid: Combination of pro-drug and nano-micelle strategy to address the curcumin challenge

- Curcumin modified with hyaluronic acid was prepared
- Modified curcumin self-assembled into nano-micelle in water
- The nano-micelle was loaded with curcumin successfully
- The combined strategy was attempted to tackle the challenges of curcumin

Curcumin is well known for its pleiotropic activities such as anti-oxidant, anti-inflammatory and anti-tumor properties. But curcumin has extremely low solubility in aqueous medium which limits its potential applications in food and pharmaceutical industries. In this study, the combined pro-drug and nano-micelle strategy was attempted to address the limitation. We modified curcumin with hyaluronic acid (HA) based on the understanding that the hydrophilic polymer facilitates dissolution of curcumin in water. The amphiphilic curcumin derivative self-assembled into nano-micelle in water with the size around 100 nm and low PDI (< 0.3) which indicated that it had narrow size distribution. FT-IR spectrum verified that curcumin was successfully conjugated onto the backbone of HA. On the other hand, curcumin was also loaded into the hydrophobic core of the nano-micelle which worked as carrier for it. Using this combined strategy, the water solubility of curcumin was increased more than 1100 times compared to the pure curcumin. The morphology characteristic of curcumin loaded nano-micelle was examined by TEM which confirmed that curcumin loaded nano-micelle has spherical shape and unified size distribution. Meanwhile, the antioxidant activities of the nano-micelle and the curcumin loaded nano-micelle were examined by DPPH radical scavenging assay and reducing power assay the results of which indicated that the antioxidant potentials were significantly enhanced. The pro-drug and nano-micelle combined method reported here may be promising to address the curcumin challenge such as low water solubility and low availability.