Otimização da extração de antocianinas de Hibiscus sabdariffa L. via solventes eutéticos profundos naturais (NADES) para a obtenção de um hidrogel de HPMC

Abstract

The anthocyanins from Hibiscus sabdariffa L. are known for their antioxidant, anti-inflammatory, and antimicrobial activity, but their chemical instability in the presence of pH, temperature, and oxygen limits their application. The objective of this study was to optimize the extraction of these anthocyanins using Natural Deep Eutectic Solvents (NADES) and to employ them in the preparation, characterization, and safety evaluation of a hydroxypropylmethylcellulose (HPMC) hydrogel as a delivery system. Seven eutectic systems were screened by ultrasound-assisted extraction, using total anthocyanin content as the selection criterion. The lactic acid:glycerol:citric acid (LAT:GLY:CIT) system exhibited the highest content (10.63 mg/mL) and high antioxidant activity, and was selected for optimization using Box-Behnken design and response surface methodology, in which sonication time was the most significant factor; the optimal condition (270 W, 20–50 °C, 15 min) yielded 6.52 mg/mL, with thermal robustness between 20 and 50 °C. Characterization by UPLC-QToF-MS/MS and HPLC-DAD identified delphinidin-3-O-sambubioside and cyanidin-3-O-sambubioside as the major anthocyanins, while FTIR revealed the integration of the pigments into the NADES hydrogen-bond network. The eutectic extract retained 72.6% of the anthocyanins after 28 days at room temperature, compared to 36.0% for the ethanolic extract. Four 3% HPMC hydrogels were developed, exhibiting a density close to that of water and spreadability compatible with topical formulations, in which the extract/NADES acted as a plasticizer. The formulations containing NADES exhibited a pH favorable for the stabilization of the flavyl cation, and the preliminary HET-CAM assay indicated no irritation from the gel formulations. The results demonstrate that the LAT:GLY:CIT system constitutes an efficient green platform for the extraction, stabilization, and topical delivery of anthocyanins in an HPMC matrix.