Enhanced lymphatic transport of bioactive lipids: cell culture study of polymethoxyflavone incorporation into chylomicrons

Abstract

Polymethoxyflavones (PMFs) are bioactive flavonoids found in citrus fruits that have been shown to have potential health promoting properties. However, their application as nutraceuticals in functional foods and beverages is currently limited due to their low water solubility and high melting point. The oral bioavailability of lipophilic compounds can be enhanced by promoting their intestinal lymphatic transport through co-administration with digestible lipids. We investigated the effects of chylomicron-mediated intestinal lymphatic transport on the bioavailability of 5-hydroxy-6,7,8,3',4'-pentamethoxylflavone (5-HPMF), one of representative PMFs in Caco-2 cells. Our results demonstrated that oleic acid and bile acid promoted secretion of chylomicrons in Caco-2 cells, with mean diameter ranged from 70 to 150 nm. The intracellular level of 5-HPMF increased 3-fold by co-incubation with the mixed micelle solution. Moreover, the basolateral level of 5-HPMF increased 3-fold due to enhanced chylomicron-mediated transport. Overall, our results demonstrated for the first time that the bioavailability of polymethoxyflavones can be enhanced by promoting their incorporation into chylomicrons.

Controlling the gastrointestinal fate of nutraceutical and pharmaceutical-enriched lipid nanoparticles: From mixed micelles to chylomicrons

“…of fatty acids were prepared using a method described previously (Mingfei Yao, 2013). Three 120 types of mixed micelles were prepared: oleic acid-sodium taurocholate (C18:1-TC); linoleic 121 acid-sodium taurocholate (C18:2-TC) and linolenic acid-sodium taurocholate (C18:3-TC), with 122 the same fatty acid-to-TC molar ratio of 1.6:0.5.…”

“…The purpose of the current study was to examine the 90 influence of fatty acid type (C18:1, C18:2, C18:3) on the formation and structure of mixed 91 micelles, lipid droplets, and chylomicrons, as well as on the incorporation of a bioactive 92 lipophilic agent, 5DN into the chylomicrons. 5DN is high lipophilic nutraceutical mainly found 93 in the citrus fruits and has been reported to have various beneficial biological effects (Mingfei 94 Yao, 2013). The current study is particularly important as polyunsaturated fatty acids have been 95 increasingly utilized in the human diet due to their potential beneficial health effects in human 96 (Nelson, 2005) Inc., MA, USA) containing polyester filters (3 m pore size and 4.7 cm 2 surface area) and grown 113 for 21 days.…”

“…Our previous research using a Caco-2 cell culture model demonstrated that mixed micelles, 87 consisting of oleic acid and sodium taurocholate, increased the trans-intestinal transport of an 88 encapsulated lipophilic nutraceutical, 5-demethylnobiletin (5DN), by promoting its incorporation 89 into chylomicrons (Mingfei Yao, 2013). The purpose of the current study was to examine the 90 influence of fatty acid type (C18:1, C18:2, C18:3) on the formation and structure of mixed 91 micelles, lipid droplets, and chylomicrons, as well as on the incorporation of a bioactive 92 lipophilic agent, 5DN into the chylomicrons.…”

Boosting the bioavailability of hydrophobic nutrients, vitamins, and nutraceuticals in natural products using excipient emulsions

“…The type of lipid phase used has been shown to influence the nature of the mixed micelles formed under simulated small intestinal conditions, as well as the nature of the oil bodies and chylomicrons formed in epithelium cells (Figure 9). Consequently, lipid type may influence the absorption of bioactive components, and their subsequent GIT fate (Yao et al, 2013;Yao et al, 2014). The nature of the lipid phase in nanoemulsions has been shown to influence the absorption of pterostilbene using a cell culture model (Sun et al, 2015).…”

The role of the food matrix and gastrointestinal tract in the assessment of biological properties of ingested engineered nanomaterials (iENMs): State of the science and knowledge gaps

“…As discussed above, what is needed is development of in vitro and in vivo methods for studying transformations of iENMs in the GIT, and identifying structure activity relationships that influence absorption and accumulation. Methods such as simulated GIT models that include mouth, stomach, and small intestine phases that mimic the fluid compositions, incubation times, and flow/pressure conditions of the GIT are crucial for assessing ENM transformations and interactions with food matrices (Arroyo-Maya and McClements, 2016; Cho et al , 2014; Lopez-Pena et al , 2016; Mun et al , 2007; Mun et al , 2006; Ozturk et al , 2015; Park et al , 2007; Qiu et al , 2015; Sandra et al , 2008; Yao et al , 2013; Yao et al , 2015a; Yao et al , 2014; Zou et al , 2015a; Zou et al , 2015b). In future work, it may be useful to employ the newly developing “omic” approaches to better understand the potential toxicity of nanoparticles, e.g., metabolomics, proteomics, and transcriptomics.…”