The Impact of Polymeric Nanoencapsulation on the Bioavailability of Lutein.
Kamil, Alison.
2014
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Abstract: Lutein, a
fat-soluble xanthophyll, contributes partially to the health benefits from consuming
plant foods. Like all dietary carotenoids, lutein has a low bioavailability. In addition
to increasing the intake of lutein-rich foods to enhance lutein status, delivery of
lutein in polymeric nanoparticles (NP) presents a novel approach to enhancing lutein
bioavailability. The overall ... read moreresearch objective of this project was to investigate, in
rats, the impact of nanoencapsulation using poly(lactic-co-glycolic acid) (PLGA) on the
pharmacokinetics of lutein. We also used an in vitro cell culture approach utilizing
human epithelial colorectal adenocarcinoma (Caco-2) cells grown in both conventional
(CONV) and permeable support (PS) systems to investigate the impact of PLGA-NP on the
absorption of lutein in intestinal cells. In chapter one, we compared the efficacy of
lutein absorption in vitro using Caco-2 cells grown in both CONV and PS systems. We
further examined the role of the micelle, the physiological vehicle for lutein within
the small intestine, on its intestinal absorption in vitro compared to an organic
solvent, ethanol, which is safe and consumed by humans. The finding from this study
demonstrated that the CONV system displayed a larger efficacy of lutein uptake by Caco-2
cells. Further, in the PS system, micelle components appeared to facilitate more
effective intestinal secretion of lutein. These findings suggest that lutein uptake by
Caco-2 cells is subject to the influence of culturing system (CONV vs. PS) and delivery
vehicle (ethanol vs. micelle). Chapter two examined the impact of PLGA-NP in rats on
lutein pharmacokinetics in plasma and distribution in selected tissues as compared to
free lutein. We also investigated the effect of nanoencapsulation on the absorption of
lutein in intestinal cells compared to a more physiological vehicle, the micelle, using
the PS method. In addition, we explored the need of additional micelles for the ultimate
absorption of lutein loaded in a water soluble NP. The findings of the rat study
indicated that, compared to free lutein, PLGA-NP improved the pharmacokinetics (Cmax and
AUC) of lutein in the plasma of rats and in general promoted lutein accumulation in
mesenteric adipose tissue and spleen but not liver. Yet, compared to micellized lutein,
although NP improved the maximal concentration of lutein in the plasma of rats as well
as in selected tissues it decreased the cell uptake and secretion of lutein in Caco-2
cells. The negative effect of the NP on cell uptake and secretion was partially remedied
by the addition of micelle components. These findings suggest that the delivery of
lutein within polymeric NP appears to be a promising approach to improving the
bioavailability of lutein in rats. The inconsistent results between the rat and cell
culture models warrant further investigations to determine which approach better
predicts responses in humans. Further, bile salts and phospholipids, which are necessary
to stimulate synthesis and secretion of chylomicrons, appear to facilitate more
effective intestinal secretion of PLGA-NP lutein. In summary, with Caco-2 cells cultured
in the PS system reliably grown to display phenotypes and functions of enterocytes in
the small intestine, this in vitro platform enables the generation of information that
is closer to the physiology of the absorptive enterocytes. However, although the CONV
system has the physiological attributes of colonic tissue, it appeared to display a
greater efficacy of lutein uptake by Caco-2 cells which can provide a rapid preliminary
tool for methodology development for nutrient absorption studies. Further, the delivery
of lutein in polymeric NP appears to be a promising approach to improve the
bioavailability of lutein in vivo but raises issues with regard to the comparability and
the predictive value of in vitro models to in vivo
responses.
Thesis (Ph.D.)--Tufts University, 2014.
Submitted to the Dept. of Biochemical and Molecular Nutrition.
Advisor: Oliver Chen.
Committee: Jeffrey Blumberg, Eric Decker, and Donald Smith.
Keywords: Nanotechnology, and Nutrition.read less - ID:
- bg257s23g
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