Introduction: Delivery systems exhibited potential in masking undesirable taste and improving solubility and/or permeability of food-derived bioactives. Despite the excellent functionality of synthetic polymers or lipids, when it comes to foods and nutraceuticals, strict regulations rule out their use in food ingredients. Bearing this in mind, we engineered 3 nanoemulsions (NEs) of similar particle size (160-200 nm) using food-grade emulsifiers of different classes: a protein (whey protein isolate, WPI), a polysaccharide (modified starch) and a synthetic polymer (polysorbate 80). We sought to understand their fate under gastrointestinal conditions and thus to evaluate their potential for delivering a model nutraceutical to different target regions in the gastrointestinal tract (GIT). Methods: The NEs were prepared using a Microfluidizer. Emulsifiers at various concentrations (1-10% w/w) were investigated to generate the NEs while keeping the oil content (soybean oil) at 10%. The model nutraceutical, coenzyme Q10 (10% w/w), was dissolved in oil prior to microfluidizing. The particle size and colloidal stability in the GIT was analysed with a DLS technique and the zeta-potential was evaluated with an LDA technique, both using Malvern Zeta-Sizer. The morphology changes in simulated gastric and intestinal fluids (SGF and SIF) were visualized by confocal laser scanning microscopy (CLSM)1. The intestinal digestion profile was measured by quantifying the release of fatty acids following pancreatin-mediated lipolysis. The Q10 bioaccessibility2 (micellized fraction) was determined by HPLC following digestion in SGF and SIF. Results: The WPI and polysorbate 80 both showed excellent emulsifying capacity at low concentration (1-2% w/w), while 10% of OSA-modified starch was needed to obtain the same particle size. All formulations achieved 100% Q10 encapsulation efficiency and 1% loading. The WPI-based NEs flocculated in SGF, while the starch-based systems were gastric resistant and eventually digested in SIF (Fig 1A). The polysorbate 80-based formulation maintained its integrity in both SGF and SIF. The NE release rate was in line with their stability profile (Fig 1B), while WPI and polysorbate 80-based NEs led to much higher Q10 bioaccessibility (> 80%) than those emulsified by modified starch (~ 40%). Conclusion: This work confirmed that natural ingredients like milk protein or grain polysaccharide are able to form NE systems suitable for oral delivery of nutraceuticals. The WPI emulsions underwent digestion in the gastric stage, ideal for quick release of nutrients. The starch-based systems offered gastric protection and targeted delivery to the small intestine. The polysorbate 80 NE is expected to pass through both stomach and small intestine to deliver nutrients to the colon.