Fabrication and characterization of a bilayered system enabling sustained release of bioflavonoids derived from mandarin biomass

Food-grade hydrogels, those prepared with Generally Recognized as Safe (GRAS) polymers, are promising delivery systems. In this work, alginate hydrogels were studied for their ability to uphold flavonoids laden poly-lactic-co-glycolic acid (PLGA) nanoparticles, and their subsequent release pattern was observed through in vitro gastrointestinal environments. Flavonoids were derived from mandarin peels, and consisted of polymethoxyflavones, chiefly tangeretin and nobiletin, and flavanones, chiefly naringenin. Incorporating these into nanoparticles prepared from GRAS classified PLGA, hereinafter referred to as flavonoids-PLGA nanoparticles, offered the first layer of protection, which were then embedded into alginate hydrogels, offering the second layer of protection. This bilayered system was developed to ensure guarded passage of the bioactives through the severe gastric environment, which would otherwise lead to presystemic metabolism of the flavonoids, rendering them ineffective. The gels were characterised and a 6.0% alginate hydrogel was considered optimal as it offered a dense network, as confirmed by a field emission scanning electron microscope (FE-SEM) image, and a low porosity, which ensured retention of the nanoparticles. Gel rheology revealed the shear thinning behavior of hydrogels, and high resistance to deformation was observed for 6% hydrogel when subjected to a load of 500N. Subjecting the ensemble to gastrointestinal environments showed a negligible 4.0% release of flavonoids in the first 2 hours of the gastric phase, followed by a sustained release through the next 10 hours in the intestinal environment, as confirmed by mass spectrometry (MS) profiles. Confocal laser scanning microscope (CLSM) images of the hydrogel clearly revealed the pH-responsive swelling and release of the nanoparticles from the hydrogel in the intestinal phase. It is envisaged that these, and other similar findings, would eventually manifest into ‘functional hydrogels’ delivery systems that bear the ability to incorporate nutraceuticals whilst retaining their functionality, as viable products in the near future.