From Analytical Profiling to Liposomal Delivery: Cannabinol as a Model for Antioxidant Encapsulation and Diffusion Enhancement

This study explores the antioxidant potential and delivery performance of five structurally distinct cannabinoids, with a particular focus on cannabinol (CBN). Comprehensive structural characterization using mass spectrometry (MS) and nuclear magnetic resonance (NMR) revealed key molecular features relevant to antioxidant function. Among the tested compounds, CBN exhibited the most potent and balanced radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl, and superoxide radicals. Based on these findings, CBN was selected for formulation into soy lecithin liposomes. The resulting CBN-loaded liposomes displayed favorable colloidal properties, with an average size of approximately 122.9 ± 0.4 nm. Results indicating increased membrane order upon CBN incorporation suggest enhanced stability of the liposomal bilayer. Antioxidant activity assays showed that CBN-loaded liposomes retain significant radical scavenging capacity, though with a moderate reduction compared to free CBN. EPR imaging further demonstrated superior diffusion of liposomal CBN through a gelatin-based semi-solid model compared to the control solution. While the current model does not replicate skin architecture, it provides a cost-effective and reproducible platform for early-stage screening of formulation mobility. These results position CBN-loaded liposomes as a promising candidate for dermal antioxidant applications, combining favorable physicochemical properties with enhanced diffusion behavior.