| Summary: | Nanotechnology has revolutionized dermocosmetic innovation by improving the stability, bioavailability, and efficacy of active ingredients. In this study, we developed and optimized a novel xanthan gum-based hydrogel containing quercetin-loaded chitosan lactate nanoparticles for antioxidant and antimicrobial skincare applications. Chitosan was converted to its lactate form to enhance water solubility and enable nanoparticle formation at physiological pH via ionic gelation with citric acid. The formulation was optimized using Box–Behnken response surface methodology to achieve minimal particle size and maximal zeta potential. The final gel was structured with xanthan gum as the gelling polymer, into which the optimized nanoparticles were incorporated to create a stable and bioactive hydrogel system. Encapsulation efficiency was measured separately to assess the effectiveness of drug loading. The optimized nanoparticles exhibited a mean diameter of 422.02 nm, a zeta potential of +29.49 mV, and a high quercetin encapsulation efficiency (76.9%), corresponding to the proportion of quercetin retained in the nanoparticle matrix relative to the total amount initially used in the formulation. Antioxidant assays (TAC, DPPH, and reducing power) confirmed superior radical-scavenging activity of the nanoformulation compared to the base hydrogel. Antibacterial tests showed strong inhibition against <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i>, and <i>Staphylococcus aureus</i>, with MIC values comparable to streptomycin. Accelerated stability studies demonstrated excellent physicochemical and microbiological stability over 60 days. This natural, bioactive, and eco-friendly formulation represents a promising platform for next-generation cosmeceuticals targeting oxidative stress and skin-related pathogens.
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