A Comparative Study of the Influence of Lipid Composition on Stability, In Vitro Release, and Antioxidant Activity of Quercetin-loaded Ceramide-containing Liposomes for Topical Delivery

Abstract This study investigates the influence of phospholipid saturation by comparing hydrogenated soy phosphatidylcholine (HSPC) and egg yolk phosphatidylcholine (EPC) on the physicochemical characteristics, colloidal stability, drug release behavior and antioxidant activity of quercetin-loaded ceramide-containing liposomes for topical delivery. Liposomes composed of EPC:Cer:Que and HSPC:Cer:Que were prepared by thin-film hydration followed by sonication. The nanosystems were studied for particle size, polydispersity index, ζ-potential, and entrapment efficiency. Colloidal stability was evaluated under mechanical stress, accelerated aging, and long-term storage, while in vitro drug release, drug retention, and antioxidant activity were assessed under simulated skin conditions. Incorporation of ceramides into EPC bilayer reduced stability issues associated with unsaturated phospholipids and maintained a fluid structure, promoting drug release. Both formulations exhibited enhanced colloidal stability with EPC-based liposomes maintaining their properties at all conditions, whereas HSPC-based liposomes showed increased particle size following mechanical stress. HSPC-based liposomes demonstrated higher quercetin entrapment efficiency (63 ± 5%), improved retention over time (75% at 90 days), and a more sustained release (45% at 480 min). EPC-based ceramide-containing liposomes exhibited faster release (50% at 240 min), resulting in greater antioxidant activity as indicated by DPPH assay (0.474 ascorbic acid equivalents), while FRAP assay results were comparable for both formulations (0.012 Fe 2+ equivalents), indicating consistent ferric reducing potential after release. These findings highlight the significance of phospholipid composition in liposome behavior and provide insights into the design of stable and effective ceramide-containing nanosystems for topical delivery of poorly water-soluble compounds such as quercetin, with potential applications in managing photoaging, inflammation, and wound healing. Graphical Abstract