Development of Ecofriendly Carbon Dots for Improving Solubility and Antinociceptive Activity of Glycyrrhizic Acid

The therapeutic potential of glycyrrhizic acid (GA) with various pharmacological properties is extremely limited owing to its poor water solubility. To solve this problem, nanocarrier-nontoxic Glycyrrhizae Radix et Rhizoma-derived carbon dots (GRR-CDs) with a narrow particle distribution of (1.90 ±0.44) nm were developed by an ecofriendly, simple and low-cost calcination method using GRR as the sole precursor. Then, the solubility of GA was shown to be prominently improved up to 27 times by GRR-CDs via a convenient and cost-effective ultrasonic dispersion method without needing to add any organic reagent. Various technologies were further used to demonstrate the interaction between GA and GRR-CDs. In addition, a release study in vitro exhibited a sustained release of GA for 24 h with a higher release ratio of up to 92.87% compared with that of pure GA. A significantly higher antinociceptive activity of the GRR-CDs-GA complexes compared to unprocessed GRR-CDs and GA was further demonstrated in both hot-plate model and acetic acid-induced writhing model. These results support the promising application of GRR-CDs as a potential tool for improving the solubility and antinociceptive activity of poorly water-soluble drugs, such as GA.