Nanostructured Lipid Carriers Enriched Hydrogels for Skin Topical Administration of Quercetin and Omega-3 Fatty Acid

Chronic skin exposure to external hostile agents (e.g., UV radiation, microorganisms, and oxidizing chemicals) may increase oxidative stress, causing skin damage and aging. Because of their well-known skincare and protective benefits, quercetin (Q) and omega-3 fatty acids (ω₃) have attracted the attention of the dermocosmetic and pharmaceutical sectors. However, both bioactives have inherent properties that limit their efficient skin delivery. Therefore, nanostructured lipid carriers (NLCs) and enriched PFC^® hydrogels (HGs) have been developed as a dual-approach vehicle for Q and/or ω₃ skin topical administration to improve bioactives' stability and skin permeation. Two NLC formulations were prepared with the same lipid composition but differing in surfactant composition (NLC1-soy lecithin and poloxamer 407; NLC2-Tween^® 80 and dioctyl sodium sulfosuccinate (DOSS)), which have an impact on physicochemical properties and pharmaceutical and therapeutic performance. Despite both NLCs presenting high Q loading capacity, NLC2's physicochemical properties make them more suitable for topical skin administration and ensure longer colloidal stability. Additionally, NLC2 demonstrated a more sustained Q release, indicating higher bioactive storage while improving permeability. The occlusive effect of NLCs-enriched HGs also has a positive impact on skin permeability. Q-loaded NLC2, with or without ω₃, -enriched HGs demonstrated efficacy as antioxidant and photoprotective formulations as well as effective reduction in S. aureus growth, indicating that they constitute a promising approach for topical skin administration to prevent skin aging and other damaging cutaneous processes.