Gastrointestinal Stability of Lipophilic Polyphenols is Dependent on their Oil-Water Partitioning in Emulsions: Studies on Curcumin, Resveratrol, and Quercetin.

Many lipophilic polyphenols have low bioavailability because of their poor solubility and chemical stability within the human gut. The encapsulation of these polyphenols within digestible lipid droplets can improve their solubility and stability. However, there is currently a poor understanding of how the molecular and physicochemical properties of specific polyphenols impact these characteristics. In this study, the factors influencing the solubility and stability of different polyphenols (curcumin, resveratrol, and quercetin) under simulated gastrointestinal conditions were examined when they were delivered in the form of soybean oil-in-water nanoemulsions containing quillaja saponin-coated droplets ( ≈ 0.15 μm; ζ = -63 mV; pH 5). The polyphenols were loaded into the lipid droplets using a pH-driven method, which is based on the pH-dependent electrical charge, oil-water partitioning, and water-solubility of these molecules. The encapsulation efficiency of all three polyphenols was relatively high (75-87%). However, their chemical stability under gastrointestinal conditions (i.e., the % remaining after exposure to gastrointestinal conditions) differed considerably: quercetin (44%), curcumin (92%), and resveratrol (100%). This effect was mainly attributed to the lower logD value of quercetin (2.17) than those of resveratrol (3.39) and curcumin (4.12). As a result, a high fraction (>50%) of quercetin was located within the aqueous gastrointestinal fluids, where it would be more prone to chemical degradation or precipitation. The fraction of the polyphenols solubilized in the gastrointestinal fluids (bioaccessibility) followed a different trend: curcumin (57%) < quercetin (73%) < resveratrol (76%). This effect was attributed to the chemical instability and/or binding of curcumin with other molecules in the simulated intestinal conditions. These results provide useful information for designing nanoemulsion-based delivery systems to improve the efficacy of lipophilic polyphenols.