Co-Amorphous Systems Based on Dihydroquercetin and l-Lysine: Synthesis and Evaluation.

Background/

Objectives

Dihydroquercetin (DHQ), also known as taxifolin, is a natural flavonoid which has anti-inflammatory and wound-healing biological effects. One of the main limitations for developing formulations with DHQ is its low solubility in water at room temperature. One of the high-potential co-formers for increasing its solubility is l-lysine, which has an aliphatic amino group in the side radical capable of entering into intermolecular interactions with the phenolic hydroxyl groups of DHQ.

Methods

Several modifications were obtained using grinding, drying, and lyophilization methods. Subsequent evaluation was conducted using a combination of physicochemical and biological analytical methods.

Results

Obtained modifications could be described as very easily soluble substances. The absence of the formation of new covalent bonds between the compounds during the formation of such systems was established. The glass transition effect was detected at 64 °C for the obtained films. It is important to note that as a result of studying the cytotoxic properties of the objects, a decrease in cytotoxicity was established during lyophilization of the mechanical mixture of the initial components. For these lyophilizates, the IC50 value was 0.025 mg/mL, 0.068 mg/mL, 0.145 mg/mL, and 0.288 mg/mL for the 3T3, HEK293, Caco-2, and HUVEC cell lines, respectively.

Conclusions

Co-amorphous systems of DHQ and l-lysine in the form of films and lyophilizates were obtained and described. These objects may be interesting from the point of view of increasing the solubility of natural flavonoids, which solves one of the main problems in developing drugs based on them.