Advances in emulsion-based delivery systems for nutraceuticals: Utilization of interfacial engineering approaches to control bioavailability.

Designing functional foods fortified with nutraceuticals is an important focus of modern food science with the aim of improving human health and wellbeing. However, many nutraceuticals have a low water solubility and poor physiochemical stability, which makes it challenging to incorporate into food matrices. Moreover, nutraceuticals may also have a low bioavailability after oral administration because they can either precipitate or chemically degrade, and/or might not be absorbed in the gastrointestinal tract. Numerous strategies have been developed and applied to encapsulate and deliver nutraceuticals. Emulsions are a kind of colloid delivery system where one phase is dispersed into another immiscible phase in the form of small droplets. These droplets have been widely used as carriers to improve the dispersibility, stability, and absorption of nutraceuticals. Many factors affect the formation and stability of emulsions, with the interfacial coating formed around the droplets by emulsifiers and other stabilizers being one of the most important. Hence, interfacial engineering principles are needed for the design and development of emulsions. Different approaches to interfacial engineering have been developed, which can help to modulate the dispersibility, stability, and bioavailability of nutraceuticals. This chapter summarizes recent research in developing interfacial engineering approaches and their impacts on the bioavailability of nutraceuticals.

In Vivo Reversal of P-Glycoprotein-Mediated Drug Resistance in a Breast Cancer Xenograft and in Leukemia Models Using a Novel, Potent, and Nontoxic Epicatechin EC31.

The modulation of P-glycoprotein (P-gp, ABCB1) can reverse multidrug resistance (MDR) and potentiate the efficacy of anticancer drugs. Tea polyphenols, such as epigallocatechin gallate (EGCG), have low P-gp-modulating activity, with an EC50 over 10 µM. In this study, we optimized a series of tea polyphenol derivatives and demonstrated that epicatechin EC31 was a potent and nontoxic P-gp inhibitor. Its EC50 for reversing paclitaxel, doxorubicin, and vincristine resistance in three P-gp-overexpressing cell lines ranged from 37 to 249 nM. Mechanistic studies revealed that EC31 restored intracellular drug accumulation by inhibiting P-gp-mediated drug efflux. It did not downregulate the plasma membrane P-gp level nor inhibit P-gp ATPase. It was not a transport substrate of P-gp. A pharmacokinetic study revealed that the intraperitoneal administration of 30 mg/kg of EC31 could achieve a plasma concentration above its in vitro EC50 (94 nM) for more than 18 h. It did not affect the pharmacokinetic profile of coadministered paclitaxel. In the xenograft model of the P-gp-overexpressing LCC6MDR cell line, EC31 reversed P-gp-mediated paclitaxel resistance and inhibited tumor growth by 27.4 to 36.1% (p < 0.001). Moreover, it also increased the intratumor paclitaxel level in the LCC6MDR xenograft by 6 fold (p < 0.001). In both murine leukemia P388ADR and human leukemia K562/P-gp mice models, the cotreatment of EC31 and doxorubicin significantly prolonged the survival of the mice (p < 0.001 and p < 0.01) as compared to the doxorubicin alone group, respectively. Our results suggested that EC31 was a promising candidate for further investigation on combination therapy for treating P-gp-overexpressing cancers.