Chitosan-coated liposomes loaded with phenolics from macadamia husk for improving their stability and in vitro bioaccessibility

Globally, macadamia nut production generates substantial amounts of by-products such as macadamia husk, which is rich in phenolic compounds known for their antioxidant and health benefits (1) . In this study, we encapsulated a phenolic-rich extract from macadamia green husk into soy-lecithin liposomes and applied a chitosan biopolymer coating to protect phenolic integrity, enhance physical stability (2) , and improve delivery for food applications (3) , as the phenolic compounds are often unstable and susceptible to environmental conditions such as heat, light, enzymes, and pH. Liposomes were prepared in aqueous media by high-pressure homogenization (2,000 MPa) and subsequently coated with 0.4% (w/v) chitosan. Particle size, ζ-potential, and polydispersity index (PDI) were measured by dynamic light scattering, morphology was assessed by transmission electron microscopy (TEM), and encapsulation efficiency (EE) was determined by quantifying free total phenols (unencapsulated phenolics). In vitro bioaccessibility was evaluated by measuring total phenolic content during an in vitro simulated gastrointestinal digestion. Empty and extract-loaded liposomes had mean diameters ranging between ~77 to 112 nm. Chitosan coating increased vesicle size (empty: 523 nm; loaded: 501 nm) and produced a broader size distribution (PDI = 0.41). Uncoated liposomes were strongly anionic (ζ = −62 mV empty; −43 mV loaded); chitosan coating reversed the surface charge to strongly positive values of +48 mV for empty and +50 mV for loaded liposomes, indicating successful adsorption of the cationic polymer. TEM confirmed largely spherical vesicles with sizes consistent with those measured by dynamic light scattering. Coated liposomes achieved higher encapsulation efficiency (91.15%) than uncoated liposomes (81.50%). Simulated digestion showed that liposomal encapsulation provided good protection under gastric (low pH) conditions but lost membrane integrity under intestinal conditions, releasing the phenolic compounds. The release of phenolic compound from coated liposomes was lower than uncoated liposomes. These results demonstrate that chitosan-coated liposomes improve the stability and in vitro bioaccessibility of macadamia husk-derived phenolics and provide practical design guidance for the development of liposomal delivery systems in food and pharmaceutical applications.