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Edible Nanoencapsulation Vehicles for Oral Delivery of Phytochemicals: A Perspective Paper Jie Xiao, Yong Cao, and Qingrong Huang J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.7b02128 • Publication Date (Web): 24 Jul 2017 Downloaded from http://pubs.acs.org on July 28, 2017
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Journal of Agricultural and Food Chemistry
Edible Nanoencapsulation Vehicles for Oral Delivery of Phytochemicals: A Perspective Paper Jie Xiao † Cao Yong † and Qingrong Huang ‡,*
†
Department of Food Science, College of Food Science, South China Agricultural
University, Guangzhou 510640, China ‡
Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick,
New Jersey 08901, USA * To whom correspondence should be addressed. Tel: (848)-932-5514. Fax (732) 932 6776. Email:
[email protected] 1
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ABSTRACT
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Edible nanoencapsulation vehicles (ENVs) designed for the delivery of phytochemicals have
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gained increasing research interest. The major driving force for this trend is the potential
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bioavailability enhancement effect for phytochemicals when delivered via ENVs. ENVs affect
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the bioefficacy of phytochemicals by influencing their dispersion and gastrointestinal stability,
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rate and site of release, transportation efficiency across endothelial layer, systemic circulation
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and biodistribution, as well as the regulation of gut microflora. Enhanced bioefficacy can be
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achieved by rational design of the size, surface property, matrix materials and compartment
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structure of ENVs according to properties of phytochemicals. Future investigations may lay
10
particular emphasis on examining the relevance between results gained by in vitro digestion
11
simulations and those obtained via in vivo ones, structural evolutions of ENVs during digestion
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and absorption, impacts of ENVs on the metabolism of phytochemicals, and using ENVs for
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deciphering the reciprocal interactions between phytochemicals and gut microbiota.
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KEYWORDS: edible nanoencapsulation vehicles, phytochemicals, bioefficacy, digestion,
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structural changes, gut microflora
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Introduction:
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Phytochemicals or phytonutrients are secondary metabolites widespread in fruits, vegetables,
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and herbal extracts, their varieties span a wide range of chemical structures such as phenolic
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acids, indoles, alkaloids, isothiocyanates, phytosterols and saponins.1-4 Although not essential for
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growth and development, they have received constant research fever due to their well-
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documented beneficial effects in health maintenance and disease risk reduction.5-7
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Phytochemicals in the native format or their metabolites exert health beneficial effects through
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mechanisms involving direct radical scavenging effect, inhibition of the assembly of microtubule
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and microfilament, metal chelation, protease inhibition, etc. 8, 9
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After oral intake, phytochemicals are recognized and processed by human body as
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xenobiotics, five consecutive events occurred thereafter10: (i) Digestion and degradation along
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the mouth, stomach, small and large intestine; (ii) Absorption from the digestive tract into the
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blood or lymph circulation; (iii) Biodistribution via diffusion or transportation from the
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intravascular space to extra-vascular space or body circulation; (iv) Metabolism in body tissues
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by biochemical conversion or degradation; (v) Excretion via renal, biliary or pulmonary
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pathways. During this process, the maximum plasma level of phytochemicals (cmax), the time to
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reach the maximum concentration in the blood (tmax), and the area under the curve of plasma
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levels vs. time (AUC), are characterized as “bioavailability”.14-16 And “bioaccessibility”, the
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potentially absorbable amount from the small intestinal epithelial cell line, is defined as a
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prerequisite for bioavailability. Since the minimum dosage required for phytochemicals to exert
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biological effects in vivo is evaluated by “bioefficacy”, usually demonstrated by short-term
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changes in biomarkers such as liver function, plasma lipid profiles, blood pressure, plasma
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glucose and plasma antioxidant activity,11-13 bioefficacy are thus influenced by both chemical
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nature of phytochemicals and biochemical activities happened during the above-mentioned
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physiological processes. And “bioavailability” and “bioaccessibility” are commonly measured to
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serve as references for the predicting of “bioefficacy”.
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In the following sections, processes and factors that affect bioefficacy of phytochemicals will
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be summarized, current understanding on how edible nanoencapsulation vehicles (ENVs)
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influence the bioefficacy of phytochemicals during oral administration and corresponding
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challenges and perspectives will be elaborated.
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Processes and factors that affect bioefficacy of phytochemicals
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In reality, the occurrence of phytochemicals or their metabolites at the systemic and tissue
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levels may fall in the micromolar range, and their efficacies are thus limited due to insufficient
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dose efficiency after oral administration.
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poor water solubility, their dispersion ability in stomach and small intestine are limited in the
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first place. Phytochemicals that form insoluble-complex or subject to degradation during
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digestion process also exhibit a limited bioaccessibility; When absorbed through the gut, small
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intestinal enterocytes host the cellular uptake, efflux pumping and phase I & II metabolism
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processes, the combined effects determined the bioaccessible amount of phytochemicals;
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Afterward, the absorbed phytochemicals together with those metabolites of enterocyte pass next
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into hepatocytes where extensive phase I and phase II biotransformation reactions take place.
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Such processes are on the one hand necessary for certain phytochemicals to transfer from
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precursors to active formats, on the other hand dramatically diminished the bioavailability of
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phytochemicals such as polyphenols;18-20 For certain lipophilic phytochemicals, these routines
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can be escaped by lymphatic absorption pathway.
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parent phytochemicals or their metabolites exert functional activities through circulation and
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As presented in Figure 1, for phytochemicals with
4
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After entering the systemic circulation,
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distribution in body tissues, where bioefficacy of phytochemicals are more often than not to be
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further decreased if they were quickly excreted;22 Lastly, the unabsorbed phytochemicals
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together with their digestive residues then reach to the colon, where they may be further broken
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down by the gut microflora and affect the bioafficacy indirectly.
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Edible nanoencapsulation vehicles (ENVs) for delivery of phytochemicals
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Edible nanoencapsulation vehicles (ENVs), utilizing the “generally recognized as safe”
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(GRAS) ingredients (various lipid, polysaccharides, proteins and biodegradable polymer that
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featured on the “GRAS” list) as building materials, are encapsulation and delivery vehicles with
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at least one dimension in the size range of 1-100 nm. Rational design of ENVs with controlled
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sizes, surface properties, matrix materials and compartment structure have been utilized as
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effective strategies for enhancing the bioefficacy of phytochemicals.23, 24 ENVs with different
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structural characteristics, such as nanoliposome, micelle, nanoemulsion, solid lipid nanoparticles,
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polymeric nanoparticles (nanospheres and nanocapsules), protein-polysaccharides complex
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coacervation, cyclodextrin inclusive and polymeric nanogel, vary in the phytochemical loading
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process, encapsulation efficiency, stability during digestion, drug release mechanism, and
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therefore bioefficacy enhancement principles (Table 1).
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The bioefficacy enhancement effects of ENVs are associated with their particle size, surface
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properties, matrix materials and compartment structure.25 In general, ENVs affect the bioefficacy
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of phytochemicals by influencing the dispersion and gastrointestinal stability, the rate and site of
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release, the transportation efficiency across endothelial layer, the systemic circulation and
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biodistribution, as well as the regulation of microflora metabolism processes.
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1) Influences of ENVs on dispersion and gastrointestinal stability
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The nano-scale particle size, usually in the range of tens to hundreds of nanometers, is the
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foremost characteristic property of ENVs. Such property is essential for them to remain stable in
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dispersion system due to the large surface area per unit volume. Besides, ENVs in format of
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polymeric nanoparticles, solid lipid nanoparticles or nanoemulsion further ensure the colloidal
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stability by introducing inter-particle repulsion forces and/or interfacial tension decreasing
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compounds.26-29 Both properties lift their chances of interacting with intestinal lining and
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facilitate the cellular uptake process thereafter. Loading phytochemicals within such ENVs has
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been one of the most popular research strategies to enhance dispersion property of initially water
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insoluble phytochemicals. For instance, kafirin protein based nanoparticles,
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nanocapsules,30 cyclodextrin inclusive, 31 and hydrophobically modified starch based micelles32
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have all been adapted to lift the bioavailability of curcumin by enhancing its aqueous dispersion
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property.
26
casein based
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Furthermore, the physical barrier property introduced by ENVs provides additional
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protective effects to sensitive phytochemicals through the digestive tract. 33 For example, free
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epigallocatechin gallate (EGCG) and catechin rapidly degraded under alkaline small intestinal
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fluids, encapsulation within caseinophosphopeptides/chitosan nanoparticles effectively prevented
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EGCG from oxidation,34 and catechin loaded liposomes lowered the degradation risks in
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simulated intestinal fluid.35 Except for polymeric nanoparticles, the inner compartment of water-
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in-oil-in-water double emulsions, solid lipid nanoparticles and polymeric nanogel offer shielding
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effects towards vulnerable phytochemicals to adversary pH, salt or enzymatic conditions of GI
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tract.
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2) Influences of ENVs on release profile of phytochemicals
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Overall, the digestion and release of phytochemicals in native state can be regarded as a
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dissolution process, where the solubility, stability and penetration property of phytochemicals in
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the gastrointestinal (GI) tract define key factors affecting its bioaccessibility thereafter. Once
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encapsulated within ENVs, physiological processes involve the digestion of ENVs, the release of
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phytochemicals and changes in chemical/physical state of phytochemicals. Depending on the
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chemical nature of matrix materials, the digestion site and rate of ENVs are predetermined in the
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first place (Figure 2). To be specific, the integrity of proteins based ENVs readily destroyed by
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pepsin in stomach. While starch based ENVs are subjected to amylase digestion during mouth,
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the majority of polysaccharides based ENVs experience degradation in small intestinal digestion.
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Non-starch polysaccharides, such as chondroitin sulfate, pectin, chitosan, guar gum, alginate, etc.,
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and resistance starch retain structural integrity until reaching the colon due to lack of digestive
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enzymes in stomach and small intestine, they thus serve as popular matrix candidates for colon-
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targeted ENVs. Structural collapse of protein-polysaccharides complex based ENVs and
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shrinkage or swelling of hydrogel based ENVs can be triggered by changes in pH value and salt
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concentration. 33 As for ENVs consisting of lipid phase, the release of phytochemicals occurred
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in small intestine along with the release of digestion byproducts of triglyceride. Biodegradable
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polymer (e.g. poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA)) based ENVs
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possess limited digestion rate in GI tract, and are thus more easily made their way to
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systemic circulation in intact format.
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The fabrication processes of ENVs also exert direct influences on the release profile of
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phytochemicals. Factors such as the drug loading method, loading efficiency and size of ENVs
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all work together to shift the partitioning equilibrium of phytochemicals between the
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encapsulation matrix and surrounding digestion fluids. For instance, the nanocapsule-based
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delivery vehicles diminish the burst release of phytochemicals remarkably as compared to a
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nanosphere-based delivery vehicle when both formulations possess the same encapsulation
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efficiency. And ENVs with higher loading efficiency and smaller vehicle size, more often than
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not, compromise with a higher burst release rate.36 Furthermore, the structural choice of
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encapsulation compartment actively tunes the release profile.15,37 Core-shell nanoparticles,
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double emulsions, gelled networks, multiple coating systems and “prodrug delivery systems”
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(where phytochemicals are conjugated with azo or glucoronic acids-containing polymers before
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or during the encapsulation processes, and the release of active moiety is triggered by enzymatic
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hydrolysis) are emerging approaches to retard the release rate of phytochemicals. Finally,
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accompanied with the release process, phytochemicals initially loaded within ENVs may
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undergo changes in physical dispersion state. A most striking example is the release of lipophilic
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phytochemicals from the lipid phase of ENVs, where lipophilic phytochemicals migrate into
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micelles formed by free fatty acids after the digestion of triglycerides, which facilitates the
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solubilization and subsequent cellular transportation process. 29,38,39
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3) Influences of ENVs on transportation and metabolism across endothelial layer
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The endothelium comprises a monolayer of endothelial cells that line blood and lymphatic
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vessels, through which phytochemicals enter into systemic circulation. The transportation of free
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phytochemicals cross the epithelial cell layer relies on the residence time and passive diffusion.
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For phytochemicals encapsulated within ENVs, ENVs and/or their derivative structures after
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digestion exert further influences on bioavailability by altering the residence time, the
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transportation efficiency and/or pathways (Figure 3).
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ENVs with initial size < 20 nm (or obtained after digestion) lift the paracellular permeability
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of phytochemicals. Coating materials of ENVs such as chitosan and chitosan derivatives possess
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the mucoadhesive and tight junction opening effects which prolong resistance time and enhance
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paracellular transport.40-43 For particles (or vehicles) with average size of 20 nm - 1µm, cellular
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uptake is conducted by transcellular endocytosis on the surface of enterocytes. And ENVs
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possessing positive charged groups and/or functional groups capable of forming hydrogen bonds
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with mucosal surfaces facilitate the temporary retention to mucosal membranes, although the
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same effects could also lead to reduced penetration efficiency across the mucus.44 By
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incorporating cell-penetrating ligands such as transferrin, vitamin B12, penetratin and
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oligoarginine to ENVs, the receptor-mediated cell endocytosis lead to enhanced transmembrane
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transport efficiency. With regard to the efflux pumping effect resulting from the P-glycoproteins
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(P-gp) on apical membranes of epithelial cells, higher bioaccessibility can be achieved by
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introducing efflux pump inhibitors, such as Tween 80, hyaluronic acid, chitosan, gellan gum and
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sodium alginate, as surface materials.45 Finally, when transport across the endothelial layer,
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phytochemicals loaded ENVs generally end up in endosomes or lysosomes followed by
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extensive Phase I (e.g. oxidation, reduction and hydrolysis) and Phase II (e.g. conjugation)
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enterocyte-based metabolism. In this process, ENVs contribute to enhanced bioefficacy by
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affecting the exposure time of phytochemicals to metabolizing enzymes in enterocyte. 46 As we
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have reported, the enhanced cellular antioxidant activity of EGCG after encapsulation within
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biopolymer based nanoparticles was probably due to the minimized metabolism of EGCG by
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corresponding glycosylase and methylase during the cellular transportation process. 47
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For highly lipophilic phytochemicals that have a log P (the logarithm of the oil-water
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partition coefficient (P) of phytochemicals) > 5 and a long-chain triglyceride solubility
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>50 mg/g, they may transit across the enterocyte and form chylomicrons with enterocyte
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lipoproteins,48 which then enter the systemic circulation via mesenteric lymph ducts and thoracic
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ducts. As a result, highly lipophilic phytochemicals manage to avoid hepatic first pass
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metabolism. Since lipid digestion products are needed to stimulate the production of
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chylomicrons, the degree of lymphatic transport strongly correlates with the triglyceride content
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of the lymph. ENVs with lipid phase incorporated including emulsions, liposomes, solid lipid
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nanoparticles, are therefore particularly effective delivery formats in mimicking the
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physiological conditions favorable for lymphatic absorption.49, 50 Additionally, the increase in
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membrane fluidity introduced by lipid based ENVs contribute further to the enhanced
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transcellular absorption efficiency. Several in vitro lipolysis case studies have confirmed that
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lipophilic compounds in emulsified state were digested and became bioaccessible much faster
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than their oil suspension state. 29,38,49
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4) Influence of ENVs on systemic circulation and biodistribution of phytochemicals
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Presystemic degradation of orally administrated ENVs in both gastrointestinal tract and
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endothelial cells play major roles in eliminating ENVs. Only digestive residue of ENVs find
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their way to systemic circulation and experience subsequent hepatic and/or systemic exposure.51
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Unlike the slow elimination and tissue accumulation properties of inorganic nanoencapsulation
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vehicles, ENVs usually have fast clearance rate by the mononuclear phagocytic system (MPS).25
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By rational design, the pharmacokinetic profile of phytochemical in ENVs during body
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circulation is controllable to a certain extent. In practice, hydrophilic coating of PEG acts as
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steric barrier to increase the circulation time of ENVs in blood. Take liposome coated with PEG
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for instance, PEGylation protects liposomes from opsonization and results in prolonged
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circulation time.22, 52 Similarly, biological capping materials such as chitosan or BSA protect
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ENVs from fast clearance by mimicking the physiological environment.53 The formula design of
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ENVs also actively alter the biodistribution behavior of phytochemicals in different tissues and
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organs. By far, in vivo investigations suggested that particulate ENVs with proper surface charge
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and particle size could navigate towards the leaky vasculature of cancerous tumors and passively
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target the desired cancerous tissue. 54And phospholipid composition as well as concentration of
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emulsifiers of emulsion based ENVs tune the biodistribution profile via affecting the
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lipophilicity, plasma binding properties of phytochemicals.
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gained by introducing magnetic nanoparticles, surface chemical modification and biorelevant
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ligands (oligosaccharides, antibodies, polypeptides or viral proteins, etc.) to ENVs. 56-58
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5) Influences of ENVs on the microflora metabolism process of phytochemicals
55
More precise control could be
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The unabsorbed phytochemicals loaded ENVs in upper GI tract will then proceed to the large
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intestine, where they undergo further metabolism by the gut microflora via esterase, glucosidase,
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demethylation, dehydroxylation and decarboxylation activities. And the ability of certain
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phytochemicals to interfere with microbial signaling has been recognized as a critical factor in
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evaluating their actual bioefficacy. Such effect is exerted either through the absorption of colonic
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metabolites of phytochemicals or modulation in gut microbial populations.59 Take polyphenol
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compounds for example, only 5–10% of the orally intake polyphenol is absorbed in the upper GI
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tract with the majority of them being accumulated in the large intestinal lumen and subjected to
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enzymatic activities of gut microbial community.60 The subsequently produced phenolic
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metabolites then absorbed through colonic epithelium into the systemic circulation to exert their
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bioactivities.61-64 Phytochemicals and their derived products can also affect the intestinal
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ecology, for example, the intake of flavonol-rich foods modified the composition of gut
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microbiota, exerting prebiotic-like effects.65
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Perhaps, the most remarkable influence of ENVs exerted on the microflora metabolism
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process of phytochemicals lies in the change in distribution proportion of phytochemicals
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between upper and lower GI tracts (Figure.4). For ENVs aiming to improve the absorption rate
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of phytochemicals in upper digestion tract, the available amount of phytochemicals reaching to
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colon is reduced. Herein, the “nanoparticulate curcumin delivery system” is one of the most
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appropriate examples. Without the nanoencapluation treatment, the majority of orally consumed
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curcumin would end up in lower GI tract due to its poor solubility and low transcellular
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efficiency, whereas curcumin experienced a dramatic increase in adsorption efficiency in upper
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GI tract after the nanoencapsulation treatment.
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riboflavin, quercetin, rutin and anthocyanins, that rely on the gut microbial metabolism to
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convert into more potent bioactive compounds, prevention of absorption and degradation in
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upper GI tract is desirable.65 Colon-targeted ENVs are thus fabricated using digestion resistant
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materials and/or with multilayered architectures (e.g. nanoparticles in microparticle,
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nanoparticles in hydrogel) to minimize the absorption and degradation in upper GI tract. And the
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design guideline of colon-targeted ENVs also includes a colon-specific release profile triggered
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by osmotic, pH and microflora conditions in colonic mucosa. Due to the low colonic luminal
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fluid volume, higher viscosity, and a neutral pH as compared to the upper GI tract, the low
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solubility as well as mucosal absorption of phytochemicals limits their colonic absorption.
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Therefore, even for hydrophobic phytochemicals, where the GI absorption rate is poor by
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nature, ENVs is necessary in that they minimize phytochemicals from possible degradation in
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upper GI tract, lift the dispersion property in colonic luminal fluid, promote the adhesion and
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adsorption in ileum and colon mucusa.
26,32, 66
For phytochemicals, such as resveratrol,
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Apart from the influence on available amount of phytochemicals subjected to microbiota
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methabolism, the presence of matrix materials of ENVs that co-delivered to colon exert further
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impacts on intestinal metabolism. Non-starch polysaccharides, such as cellulose, dextrins,
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chitins, pectins and waxes not only modulate the transit time through the gut but also induce
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changes in bacterial populations during partially bacterial fermentation. And microbiota derived
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products from fibers and lipids by themselves contribute to the lifted bioefficacy via protection
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against gastrointestinal disorders and pathogens, modulating immune responses, reduction in
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plasma triacylglycerol, etc.67-69
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Challenges and perspectives
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For research trends in fabrication strategies of ENVs, combining multiple structural designs,
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which either strengthen the property of one ENV or combine benefits of two or more ENVs, is
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an attractive approach for maximized effect.72-75 In the realm of target delivery, though materials
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and fabrication strategies that allow for the creation of ENVs with design freedom constantly
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growing, effective target-delivery has not yet been developed. Compared to intravenous drug
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delivery systems, orally administrated ENVs can hardly be considered as real candidates for
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tissue targeted delivery in the near future. Such an inevitable drawback roots from the high
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presystemtic degradation rate of the majority of ENVs.
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Currently, in vitro digestion simulation models of phytochemicals loaded ENVs serve as
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cost-efficient tool for predicting the oral bioavailability of phytochemicals loaded ENVs, and are
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quite efficient for comparative studies among different ENVs. The emerging trend has now
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shifted from the bottle-based static gastrointestinal systems to the computer-controlled dynamic
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gastrointestinal systems, an attempt to avoid oversimplification of the three-dimensional
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structure and mechanical movements of the gastrointestinal tract. As for cellular transportation
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investigations, in view of the fact that the widely adapted cell layer covered models (e.g., Franz
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diffusion cells, transwell-systems and Ussing chambers) fail to mimic the intestinal environment
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due to their lack of mucus producing property, cell layer models with mucus secreting
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functionality are proposed. Compiling data from relevant studies and elucidating the relevance of
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in vitro studies to in vivo pharmacokinetic trials are worth trying research attempts.
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When evaluating effects of ENVs on bioefficacy of phytochemicals, extra attention should be
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paid on experimental design. Firstly, a reliable bioefficacy assessment should consider possible
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changes in the structure of ENVs under real digestion situation. To be specific, when mixed with
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digestion fluid, the dilution effects on ENVs, such as micelles, liposomes and nanoemulsion, are
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not negligible since their structural integrity relies on maintaining surfactant concentration within
275
a narrow range. Effects of pH, ions and enzymes in the GI tract on stability of ENVs also pose a
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non-negligible impact. Therefore, studies targeting structural evolution of ENVs in complex
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matrices (i.e. real food matrices), rather than in simplified model systems, hold more practical
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significance. Moreover, when conducting comparison experiments on bioefficacy between free
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phytochemicals and ENVs encapsulated ones, possible differences in pharmacokinetic profiles of
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phytochemicals should be taken into account. For example, the existence of ENVs may change
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the internalization speed of phytochemicals, according to which the sampling points for
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biomarker detection should be adjusted accordingly.
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In addition, metabolic conversion is known as a major factor affecting phytochemical
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bioavailability. Currently, little is known about how the cellular signaling pathways differ from
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free phytochemicals and impacts of co-existence of ENVs on the metabolism of phytochemicals
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remain unanswered. There has been reports claimed that the coexistence of proline-rich proteins
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are capable of binding gallated catechins like epigallocatechingallate and convert them into non-
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gallated catechins like epigallocatechin by tannase, thus enhancing epigallocatechin
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bioavailability.70 Cleary, the hypothesis that “interaction between phytochemicals and matrix
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material of ENVs may exert effect on their metabolism and thus bioefficacy” needs further
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investigation.71 Intensive researches aiming to elucidate the correlation between the formula of
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ENVs and their metabolic profiles and biodistribution behaviors should be conducted to serve as
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a guideline in the rational design of ENVs with maximized bioefficacy and predictable in
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vivo properties.
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Lastly, not only original phytochemicals but also their microbial metabolites should be taken
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into account when assessing the bioefficacy of phytochemicals. And if the role of gut
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metabolism is considered, we have to redefine the current definition of “bioavailability” and
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“bioaccessibility”, both emphases the absorption in upper GI tract. Such concept is vital in
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rational design of ENVs based on the nature of phytochemicals. ENVs aiming at improving the
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absorption through the upper GI tract may not serve as the gold standard anymore, since for
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phytochemicals whose high bioefficacy root from gut metabolism, limited absorption in the
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upper GI tract is desirable. Currently, the reciprocal interactions between phytochemicals and gut
303
microbiota, the mechanisms of action, and the consequences of these interactions on bioefficacy
304
are still poorly understood. And the role of nanoencapsulation on the metabolism of
305
phytochemicals by microflora posts additional challenges on the already complicated situation.
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To date, the assessment of effects of nanoencapsulation on gut microbiota metabolism of
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phytochemicals in human gut has been rarely reported. Comparison studies conducted between
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phytochemicals delivered with or without accompanied ENVs will shed new light on deciphering
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the inter-relationship between phytochemicals and gut microbiota.
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Overall, encapsulate phytochemicals within appropriate ENVs lift the bioavailability of
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phytochemicals via: i) protect sensitive phytochemicals from degradation during storage and
312
gastrointestinal digestion; ii) solubility enhancement; iii) prolonged contact time with the
313
intestinal wall; iv) increase the mucus penetration and intestinal permeation; v) facilitate cellular
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uptake; vi) prolong residence time within the body circulation; vii) controlled release rate and
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site; viii) alter the microflora metabolism. The initial physicochemical aspects of ENVs, their
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digestion stability, endothelial transportation efficiency, metabolism and interactions with gut
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microbiota, govern the bioefficacy of phytochemicals. It can be foreseen that the contribution of
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ENVs will not limit to the bioefficacy enhancement of phytochemicals, but also offer a powerful
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tool to decipher the current mystery of reciprocal interactions between phytochemicals and gut
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microbiota.
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Acknowledgment
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Authors acknowledge the financial support for the first author from the China Scholarship
322 323
Council.
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References:
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constituents and pharmacological activities of pogostemon cablin benth.: An aromatic medicinal
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Phytochemical composition and bioactivities of lupin: a review. Int. J. Food Sci. Tech. 2015, 50,
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Figure Captions
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Figure 1: Processes (in blue) and key factors affecting bioefficacy (marked by bullet points) of
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phytochemical after oral intake.
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Figure 2: ENVs exert influences on release profile of phytochemicals through programed
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Figure 3: ENVs exert influences on transportation across endothelial layer of phytochemical via
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Figure 4: ENVs exert influences on the microflora metabolism process of phytochemical by 1)
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Table 1. Non-exhaustive categories of edible materials based nanoencapsulation vehicles for the delivery of phytochemicals Nanoencapsulation Systems Nanoliposome: bilayer structure composed of phospholipids (