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In this study, nanoemulsion-based delivery systems fabricated using three different methods were compared with three commercially available curcumin supplements. Powdered curcumin was dispersed into the oil-in-water nanoemulsions using three methods: the conventional oil-loading method, the heat-driven method, and the pH-driven method. The conventional method involved dissolving powdered curcumin in the oil phase (60 °C, 2 h) and then forming a nanoemulsion. The heat-driven method involved forming a nanoemulsion and then adding powdered curcumin and incubating at an elevated temperature (100 °C, 15 min). The pH-driven method involved dissolving curcumin in an alkaline solution (pH 12.5) and then adding this solution to an acidified nanoemulsion (pH 6.0). The three commercial curcumin products were capsules or tablets purchased from an online supplier: Nature Made, Full Spectrum, and CurcuWin. Initially, the encapsulation efficiency of the curcumin in the three nanoemulsions was determined and decreased in the following order: pH-driven (93%) > heat-driven (76%) > conventional (56%) method. The different curcumin formulations were then subjected to a simulated gastrointestinal tract (GIT) model consisting of mouth, stomach, and small intestine phases. All three nanoemulsions had fairly similar curcumin bioaccessibility values (74−79%) but the absolute amount of curcumin in the mixed micelle phase was highest for the pH-driven method. A comparison of these nanoemulsions and commercial products indicated that the curcumin concentration in the mixed micelles decreased in the following order: CurcuWin ≈ pH-driven method > heat-driven method > conventional method ≫ Full spectrum > Nature Made. This study provides valuable information about the impact of the delivery system type on curcumin bioavailability. It suggests that encapsulating curcumin within small lipid particles may be advantageous for improving its absorption form the GIT.

24The potential of mixed colloidal dispersions for increasing the bioaccessibility of a 25 hydrophobic bioactive agent (curcumin) was examined. Curcumin was encapsulated within zein 26 nanoparticles (fabricated by antisolvent precipitation) to obtain a high loading capacity and good 27 chemical stability. These protein nanoparticles were then mixed with digestible lipid 28 nanoparticles (fabricated by microfluidization) designed to increase curcumin bioaccessibility by 29 forming mixed micelles in the small intestine. Changes in particle properties (size, charge, and 30 organization) were measured as the mixed colloidal dispersions were passed through a simulated 31 gastrointestinal tract: mouth; stomach; small intestine. Curcumin bioaccessibility increased with 32 increasing lipid nanoparticle concentration in the mixed colloidal dispersions, which was 33 attributed to an increase in the solubilization capacity of the mixed micelle phase. This study 34 suggests that delivery systems containing mixed colloidal particles (protein and lipid 35 nanoparticles) may be designed to increase the bioaccessibility of lipophilic bioactive agents. 36 37

Curcumin is a bioactive constituent isolated from turmeric that has historically been used as a seasoning, pigment, and herbal medicine in food. Recently, it has become one of the most commonly studied nutraceuticals in the pharmaceutical, supplement, and food areas because of its myriad of potential health benefits. For instance, it is claimed to exhibit antioxidant, anti-inflammatory, antimicrobial, antiparasite, and anticancer activities when ingested as a drug, supplement, or food. Toxicity studies suggest that it is safe to consume, even at relatively high levels. Its broad-spectrum biological activities and low toxicity have meant that it has been widely explored as a nutraceutical ingredient for application in functional foods. However, there are several hurdles that formulators must overcome when incorporating curcumin into commercial products, such as its low water solubility (especially under acidic and neutral conditions), chemical instability (especially under neutral and alkaline conditions), rapid metabolism by enzymes in the human body, and limited bioavailability. As a result, only a small fraction of ingested curcumin is actually absorbed into the bloodstream. These hurdles can be at least partially overcome by using encapsulation technologies, which involve trapping the curcumin within small particles. Some of the most commonly used edible microparticles or nanoparticles utilized for this purpose are micelles, liposomes, emulsions, solid lipid particles, and biopolymer particles. Each of these encapsulation technologies has its own benefits and limitations for particular product applications and it is important to select the most appropriate one.