Many natural bioactive compounds bear various health-promoting benefits and are incorporated in functional foods. The utilization of the compounds in human body, or the bioavailability is usually not taken into consideration in the process of food formulation. In this Ph.D. study, the problem of the poor bioavailability of polyphenols, such as curcumin, was addressed by development of two nanoscale delivery systems, namely biopolymer micelles and nanoemulsions. It is known that solubilization and metabolism are two limiting factors for curcumin oral bioavailability. Using Caco-2 cell monolayers model, it was revealed that the permeation of solubilized curcumin was fast and by passive diffusion and that solubilization, not permeation of curcumin limited the absorption and the oral bioavailability. Subsequently, the solubilization of curcumin was improved by encapsulation of curcumin in biopolymer-based micelles and organogel-based formulations. Polymer micelles were generated from modified starch and self-synthesized modified epsilon polylysine. Upon encapsulation, the water solubility of curcumin was greatly increased and curcumin was stabilized against alkaline degradation. Moreover, the in vitro anti-cancer and cellular antioxidant activities of curcumin were also enhanced. On the other hand, food-grade curcumin organogel with high loading and in vitro bioaccessibility was developed. Based on the organogel, nanoemulsions were further generated to achieve faster and more complete digestion. The absorption mechanism of the nanoemulsion was examined using Caco-2 cell monolayer permeation assay and was suggested as the classic digestion-permeation route. It was further revealed that the oral bioavailability increased by 9-fold compared with unformulated curcumin on mice. Moreover, the toxicity of nanoemulsions was examined in vitro. Three tested food-grade nanoemulsions did not show significant toxicity on Caco-2 cell monolayers, which suggested that nanoemulsions may not affect the integrity of the small intestine epithelium. The biopolymer micelles and nanoemulsion formulations can be applied for oral delivery of other water-insoluble compounds for functional food application. And the formulation development method driven by absorption mechanisms also provides an example for future formulation studies.
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Food Science
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Rutgers University Electronic Theses and Dissertations
Rutgers University. Graduate School - New Brunswick
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