Polyphenol Extracts from Glycyrrhiza glabra L.: Encapsulation, Chemical Characterization, and Evaluation of Anti-Inflammatory, Anti-Proliferative, Oral, and Intraperitoneal Activities

This study analyzes the therapeutic properties of polyphenolic extracts from Glycyrrhiza glabra L. (licorice) and the efficacy of their nanoencapsulation in liposomes produced via microfluidic technology, a strategy developed to overcome the poor stability and low aqueous solubility of free phytocompounds. Phytochemical analysis revealed a profile rich in specific flavonoids and chalcones, such as liquiritin and glabridin. In biological assays, the extract-loaded liposomes (GG-Lipo) exhibited marked selective cytotoxicity against three human colorectal cancer cell lines (HT29, SW480, and CaCo2), drastically reducing their viability without affecting healthy human colonic epithelial cells (HCECs). Furthermore, the liposomal system demonstrated excellent immunomodulatory and antioxidant properties both in vitro and in vivo, significantly reducing lipid peroxidation and the levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), while restoring endogenous enzymatic defenses such as superoxide dismutase, catalase, and glutathione peroxidase. Regarding analgesic activity, animal models of chemical and thermal nociception confirmed the ability of the nanoencapsulated formulation to suppress both peripheral and central pain via supraspinal mechanisms, matching or exceeding the performance of reference drugs like acetaminophen. Finally, the 14-day toxicological evaluation highlighted that encapsulation flattens toxic plasma peaks, thereby preventing the systemic shock and mortality observed with high doses of the free extract administered intraperitoneally, validating the safety and biocompatibility of the lipid matrix for future clinical applications against cancer and related painful inflammatory conditions.