Introduction: Zein and fucoidan are biomaterials useful to obtain hybrid nanoparticles to be orally administered and employed for the treatment of inflammatory bowel disease (IBD). Zein is stable in gastrointestinal fluids while fucoidan confers mucoadhesion and intrinsic anti-inflammatory activity to the nanosystems.

Methods: Nanoparticles were obtained by nanoprecipitation using zein and fucoidan at various weight ratios and they were employed to entrap mesalazine (5-ASA). The physico-chemical properties, entrapment efficiency and release rate of the active compound in simulated gastrointestinal fluids were evaluated by dynamic light scattering, FT-IR and spectrophotometric analyses, respectively. The muco-adhesive interactions were assessed monitoring their mean diameter e and surface charge after incubation with porcine gastric mucin (0.1–0.5% w/v, 37 °C, up to 4 h). The antioxidant activity was investigated by the DPPH assay. Additional studies were performed in Caenorhabditis elegans in order to evaluate the in vivo fate of hybrid nanoparticles.

Results: Hybrid zein–fucoidan nanoparticles showed mean sizes of 100 nm, a narrow size distribution (PDI<0.2), a negative Zeta potential (ζ ≈ −55 mV) and an encapsulation efficiency of ~60% when 0.6 mg/mL of 5-ASA were used. They demonstrated to preserve the antioxidant activity of 5-ASA in simulated gastrointestinal fluid and the incubation with mucin confirmed the mucoadhesive properties of the nanosystems. In vivo studies in Caenorhabditis elegans showed a strong biocompatibility of the nanosystems, a useful intake and favorable effects on fat accumulation, oxidative stress and aging biomarkers.

Conclusions: Zein–fucoidan hybrid nanoparticles containing 5-ASA represent innovative nanomedicine to be employed for the treatment of IBD.