Preparation of Quercetin-Loaded Lipid Nanoparticle-Embedded Hydrogels and Stability Studies

Quercetin, a plant-derived flavonoid with potent antioxidant and anti-inflammatory properties, is limited for topical use by its poor aqueous solubility, low bioavailability, and chemical instability. This research developed and validated a formulation-driven strategy to stabilize quercetin by encapsulating it in lipid nanoparticles (QLNs) and embedding these in a Carbopol hydrogel, providing comprehensive physicochemical and functional stability data. A fully validated HPLC-PDA assay was used to quantify quercetin in the nanoparticle–hydrogel matrix. In vitro bioactivity testing showed notable antioxidant activity (DPPH IC50 6.84 ± 0.12 µg/mL; ABTS IC50 4.04 ± 0.08 µg/mL; FRAP 301.46 ± 3.68 µg/mL) and an anti-inflammatory effect in LPS-stimulated RAW264.7 macrophages (1 µM quercetin reduced NO from 50.72 ± 2.00 µM to 41.57 ± 3.12 µM, p < 0.05). Forced degradation mapping across acidic, basic, oxidative, and photolytic conditions defined degradation pathways (complete loss in 1 N NaOH at 24 h; greater retention in 1 N HCl, 3% H2O2, and UV-254). QLN–hydrogel formulations remained physically and chemically stable through heating–cooling cycles and 180-day storage at multiple temperatures, retaining >90% quercetin and preserving antioxidant and anti-inflammatory activities (<10% reduction). These results establish a robust, application-ready approach for maintaining quercetin’s chemical integrity and bioactivity in topical formulations.