Industrial processing of citrus fruits produces tons of peel, pulp, and seeds as by-products. Although currently considered waste, these byproducts may be inexpensive sources of bioactive compounds. For example, mandarins (Citrus nobilis X Citrus deliciosa) are a potential source of flavonoid antioxidants. However, the metabolism of flavonoids in the gut limits their potential as nutritional supplements; colloidal delivery systems that protect flavonoids from metabolism may overcome this barrier. Here, we examined the flavonoid profile of mandarin peel. To this end, dried and pulverized peels were subjected to supercritical fluid extraction, and the extract contained 47.3±1.06 mg/ml rutin equivalents of total flavonoids. Mass spectral analysis revealed the predominance of polymethoxyflavones, chiefly tangeretin and nobiletin. We tested the pre-systemic metabolism of these flavonoids in an in vitro cell-free gastric environment and observed that nearly 50% of the flavonoids degraded within the first 2 hours of gastric exposure. To limit this, we nanoencapsulated flavonoids with polylactic-co-glycolic acid to a particle size of 200–250 nm. This monolayer nanoparticle system protected flavonoids in the gastric environment, allowing only 20% to be released in the first 2 h. To further protect the flavonoids, we constructed a bilayered delivery system by embedding the nanoencapsulated flavonoids in alginate hydrogels. This achieved 100% protection from pre-systemic release of flavonoids. Cryo-scanning electron microscopy showed that the nanoencapsulated flavonoids were well encapsulated in the dense pockets of alginate hydrogel. The monolayered and bilayered systems protected the flavonoids and either could be used for functional foods, depending upon the intended application and format (for example, as a liquid-flavonoid PLGA nanoparticles or a solid formulation- nanoparticle infused hydrogel). Kinetic modeling was studied in order to depict the mechanism of release behind the delivery vehicles and it was found that the Korsmeyer–Peppas model was the best fit for monolayered system and the Higuchi model as suitable fit for the bilayered system, the difference being in the mechanism of release i.e., Fickian diffusion for the monolayered system and Supercase II transport mechanism for bilayered system. This work underpins the role of carriers in the efficient delivery of flavonoids, in addition to the importance of extracting valuable bioactives from waste, thereby leading to sustainable valorization.
