The nutraceutical bioavailability classification scheme: Classifying nutraceuticals according to factors limiting their oral bioavailability

Annual Review of Food Science and Technology

Volumn 6, Issue , 2015, Pages 299-327

  McClements, David Julian ^a,b   Li, Fang ^a   Xiao, Hang ^a  

^a UNIVERSITY OF MASSACHUSETTS   (United States)

^b KING ABDULAZIZ UNIVERSITY   (Saudi Arabia)

Author keywords

Bioactive food components; Delivery systems; Drugs; Excipient foods; Food effects; Functional foods; Lipophilic; Medical foods; Nutraceuticals; Pharmaceuticals

Indexed keywords

CLASSIFICATION (OF INFORMATION); CONTROLLED DRUG DELIVERY; DRUG PRODUCTS; FUNCTIONAL FOOD; LINEAR TRANSFORMATIONS;

BIOACTIVE FOOD COMPONENTS; DELIVERY SYSTEMS; DRUGS; FOOD EFFECT; LIPOPHILIC; NUTRACEUTICALS;

BIOCHEMISTRY;

BIOAVAILABILITY; DIET SUPPLEMENTATION; ORAL DRUG ADMINISTRATION;

ADMINISTRATION, ORAL; BIOLOGICAL AVAILABILITY; DIETARY SUPPLEMENTS;

EID: 84926508869     PISSN: 19411413     EISSN: 19411421     Source Type: Journal    
DOI: 10.1146/annurev-food-032814-014043     Document Type: Review

References (145)

1. Aarak KE, Rigby NM, Kirkhus B, Salt LJ, Sahlstrom S, et al. 2013. The impact of meal composition on the release of fatty acids from salmon during in vitro gastrointestinal digestion. Food Funct. 4:1819-26
2. Actis-Goretta L, Leveques A, Rein M, Teml A, Schafer C, et al. 2013. Intestinal absorption, metabolism, and excretion of ()-epicatechin in healthy humans assessed by using an intestinal perfusion technique. Am. J. Clin. Nutr. 98:924-33
3. Aherne SA, Daly T, Jiwan MA, O'Sullivan L, O'Brien NM. 2010. Bioavailability of beta-carotene isomers from raw and cooked carrots using an in vitro digestion model coupled with a human intestinal Caco-2
4. cell model. Food Res. Int. 43:1449-54
5. Akoh CC, Min DB. 2008. Food Lipids: Chemistry, Nutrition, and Biotechnology. Boca Raton, FL: CRC Press
6. Alfaras I, Perez M, Juan ME,MerinoG, Prieto JG, et al. 2010. Involvement of breast cancer resistance protein (BCRP1/ABCG2) in the bioavailability and tissue distribution of trans-resveratrol in knockout mice. J. Agric. Food Chem. 58:4523-28
7. Amidon GL, Lennernas H, Shah VP, Crison JR. 1995. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharma. Res. 12:413-20
8. Arnott JA, Planey SL. 2012. The influence of lipophilicity in drug discovery and design. Expert Opin. Drug Discov. 7:863-75
9. Artursson P, Palm K, Luthman K. 1996. Caco-2 monolayers in experimental and theoretical predictions of drug transport. Adv. Drug Deliv. Rev. 22:67-84
10. Azorin-Ortuno M, Yanez-Gascon MJ, Vallejo F, Pallares FJ, Larrosa M, et al. 2011. Metabolites and tissue distribution of resveratrol in the pig. Mol. Nutr. Food Res. 55:1154-68
11. Boon CS,McClements DJ, Weiss J,Decker EA. 2010. Factors influencing the chemical stability of carotenoids in foods. Crit. Rev. Food Sci. Nutr. 50:515-32
12. Borel P, Tyssandier V, Mekki N, Grolier P, Rochette Y, et al. 1998. Chylomicron beta-carotene and retinyl palmitate responses are dramatically diminished when men ingest beta-carotene with medium-chain rather than long-chain triglycerides. J. Nutr. 128:1361-67
13. Bosscher D, Breynaert A, Pieters L, Hermans N. 2009. Food-based strategies to modulate the composition of the intestinal microbiota and their associated health effects. J. Physiol. Pharmacol. 60:5-11
14. Brown MJ, Ferruzzi MG, Nguyen ML, Cooper DA, Eldridge AL, et al. 2004. Carotenoid bioavailability is higher from salads ingested with full-fat than with fat-reduced salad dressings as measured with electrochemical detection. Am. J. Clin. Nutr. 80:396-403
15. Carail M, Goupy P, Reynaud E, Dangles O, Caris-Veyrat C. 2013. Oxidative cleavage products of lycopene: production and reactivity in a biomimetic experimental model of oxidative stress. In Carotenoid Cleavage Products, ed. PWinterhalter, SE Ebeler, pp. 191-205. Washington, DC: Am. Chem. Soc.
16. Carbonell-Capella JM, Buniowska M, Barba FJ, Esteve MJ, Frigola A. 2014. Analytical methods for determining bioavailability and bioaccessibility of bioactive compounds from fruits and vegetables: a review. Compr. Rev. Food Sci. Food Saf. 13:155-71
17. Chabanea MN, Ahmad AA, Peluso J, Muller CD, Ubeaud G. 2009. Quercetin and naringenin transport across human intestinal Caco-2 cells. J. Pharm. Pharmacol. 61:1473-83
18. Challa VR, Babu PR, Challa SR, Johnson B, Maheswari C. 2013. Pharmacokinetic interaction study between quercetin and valsartan in rats and in vitro models. Drug Dev. Ind. Pharm. 39:865-72
19. CharmanWN, Porter CJH, Mithani S, Dressman JB. 1997. Physicochemical and physiological mechanisms for the effects of food on drug absorption: the role of lipids and pH. J. Pharma. Sci. 86:269-82
20. Chen ZJ, Zheng SR, Li LP, Jiang HD. 2014. Metabolism of flavonoids in human: a comprehensive review. Curr. Drug Metab. 15:48-61
21. Chi YC, Lin SP, Hou YC. 2012. A new herb-drug interaction of Polygonum cuspidatum, a resveratrol-rich nutraceutical, with carbamazepine in rats. Toxicol. Appl. Pharmacol. 263:315-22
22. Choi JS, Choi BC, Kang KW. 2009. Effect of resveratrol on the pharmacokinetics of oral and intravenous nicardipine in rats: possible role of P-glycoprotein inhibition by resveratrol. Pharmazie 64:49-52
23. Cirin DM, Posa MM, Krstonosic VS. 2012. Interactions between sodium cholate or sodium deoxycholate and nonionic surfactant (Tween 20 or Tween 60) in aqueous solution. Ind. Eng. Chem. Res. 51:3670-76
24. Cone RA. 2009. Barrier properties of mucus. Adv. Drug Deliv. Rev. 61:75-85
25. Constantinides PP, Wasan KM. 2007. Lipid formulation strategies for enhancing intestinal transport and absorption of P-glycoprotein (P-gp) substrate drugs: in vitro/in vivo case studies. J. Pharma. Sci. 96:235-48
26. Cramer JM, Jeffery EH. 2011. Sulforaphane absorption and excretion following ingestion of a semipurified broccoli powder rich in glucoraphanin and broccoli sprouts in healthy men. Nutr. Cancer 63(2):196-201
27. D'Ambrosio DN, Clugston RD, Blaner WS. 2011. Vitamin A metabolism: an update. Nutrients 3:63-103
28. Dahan A, Miller JM. 2012. The solubility-permeability interplay and its implications in formulation design and development for poorly soluble drugs. AAPS J. 14:244-51
29. DahanA,Miller JM,Amidon GL. 2009. Prediction of solubility and permeability classmembership: provisional BCS classification of the world's top oral drugs. AAPS J. 11:740-46
30. Day A, Canada F, Diaz J, Kroon P, McLaughlan R, et al. 2000. Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett. 468:166-70
31. Decker EA, Chen B, Panya A, Elias RJ. 2011. Understanding antioxidant mechanisms in preventing oxidation in foods. In Oxidation in Foods and Beverages and Antioxidant Applications, Vol. 1: UnderstandingMechanisms of Oxidation and Antioxidant Activity, ed. EA Decker, RJ Elias, DJ McClements, pp. 225-48. Cambridge, UK:Woodhead Publ.
32. Delmas D, Aires V, Limagne E, Dutartre P, Mazue F, et al. 2011. Transport, stability, and biological activity of resveratrol. Ann. N.Y. Acad. Sci. 1215:48-59
33. Dempe JS, Scheerle RK, Pfeiffer E, Metzler M. 2013. Metabolism and permeability of curcumin in cultured Caco-2 cells. Mol. Nutr. Food Res. 57:1543-49
34. Devraj R, Williams HD, Warren DB, Mullertz A, Porter CJH, Pouton CW. 2013. In vitro digestion testing of lipid-based delivery systems: calcium ions combine with fatty acids liberated from triglyceride rich lipid solutions to form soaps and reduce the solubilization capacity of colloidal digestion products. Int. J. Pharm. 441:323-33
35. Diniz A, Escuder-Gilabert L, Lopes PN, Villanueva-Cama ñasMR, Sagrado S,Medina-Hernández JM. 2008. Characterization of interactions between polyphenolic compounds and human serum proteins by capillary electrophoresis. Anal. Bioanal. Chem. 391(2):625-32
36. Dudhatra GB, Mody SK, Awale MM, Patel HB, Modi CM, et al. 2012. A comprehensive review on pharmacotherapeutics of herbal bioenhancers. Sci. World J. 2012:637953
37. During A, Hussain MM, Morel DW, Harrison EH. 2002. Carotenoid uptake and secretion by CaCo-2 cells: beta-carotene isomer selectivity and carotenoid interactions. J. Lipid Res. 43:1086-95
38. Elbarbry F, Elrody N. 2011. Potential health benefits of sulforaphane: a review of the experimental, clinical and epidemiological evidences and underlying mechanisms. J. Med. Plants Res. 5(4):473-84
39. Espin JC, Garcia-Conesa MT, Tomas-Barberan FA. 2007. Nutraceuticals: facts and fiction. Phytochemistry 68:2986-3008
40. Fahy DM, O'Callaghan YC, O'Brien NM. 2004. Phytosterols: lack of cytotoxicity but interference with beta-carotene uptake in Caco-2 cells in culture. Food Addit. Contam. 21:42-51
41. Failla ML, Huo T, Thakkar SK. 2007. In vitro screening of relative bioaccessibility of carotenoids from foods. Presented at Annu. Meet. Asian Congress of Nutr., 10th, Taipei, Taiwan
42. Fasinu P, Pillay V, NdesendoVMK,du Toit LC,ChoonaraYE. 2011. Diverse approaches for the enhancement of oral drug bioavailability. Biopharm. Drug Dispos. 32:185-209
43. Fernandez-Garcia E, Carvajal-Lerida I, Jaren-Galan M, Garrido-Fernandez J, Perez-Galvez A, Hornero-Mendez D. 2012. Carotenoids bioavailability from foods: from plant pigments to efficient biological activities. Food Res. Int. 46:438-50
44. Nielsen IL, Williamson G. 2007. Review of the factors affecting bioavailability of soy isoflavones in humans. Nutr. Cancer 57(1):1-10
45. Fleisher D, Li C, Zhou Y, Pao LH, Karim A. 1999. Drug, meal and formulation interactions influencing drug absorption after oral administration-clinical implications. Clin. Pharmacokinet. 36:233-54
46. Fong SYK, Liu M, Wei H, Lobenberg R, Kanfer I, et al. 2013. Establishing the pharmaceutical quality of Chinese herbal medicine: a provisional BCS classification. Mol. Pharma. 10:1623-43
47. Goicoechea E, Brandon EFA, Blokland MH, Guillen MD. 2011. Fate in digestion in vitro of several food components, including some toxic compounds coming from omega-3 and omega-6 lipids. Food Chem. Toxicol. 49:115-24
48. Goicoechea E, Van Twillert K, Duits M, Brandon E, Kootstra PR, et al. 2008. Use of an in vitro digestion model to study the bioaccessibility of 4-hydroxy-2-nonenal and related aldehydes present in oxidized oils rich in omega-6 acyl groups. J. Agric. Food Chem. 56:8475-83
49. Granado-Lorencio F, Olmedilla-Alonso B, Herrero-Barbudo C, Perez-Sacristan B, Blanco-Navarro I, Blazquez-Garcia S. 2007. Comparative in vitro bioaccessibility of carotenoids from relevant contributors to carotenoid intake. J. Agric. Food Chem. 55:6387-94
50. Henning MS, Niu Y, Lee HN, Thames DG, Minutti RR, et al. 2004. Bioavailability and antioxidant activity of tea flavanols after consumption of green tea, black tea, or a green tea extract supplement. Am. J. Clin. Nutr. 80:1558-64
51. Herron KL, McGrane MM, Waters D, Lofgren IE, Clark RM, et al. 2006. The ABCG5 polymorphism contributes to individual responses to dietary cholesterol and carotenoids in eggs. J. Nutr. 136:1161-65
52. Hong J, Lambert JD, Lee SH, Sinko PJ, Yang CS. 2003. Involvement of multidrug resistance-associated proteins in regulating cellular levels of ()-epigallocatechin-3-gallate and itsmethylmetabolites. Biochem. Biophys. Res. Commun. 310(1):222-27
53. Hribar U, Ulrih NP. 2014. The metabolism of anthocyanins. Curr. Drug Metab. 15:3-13
54. Hurst S, Loi CM, Brodfuehrer J, El-Kattan A. 2007. Impact of physiological, and biopharmaceutical factors in absorption and metabolism mechanisms on the drug oral bioavailability of rats and humans. Expert Opin. Drug Metab. Toxicol. 3:469-89
55. Jeffery J, Holzenburg A, King S. 2012a. Physical barriers to carotenoid bioaccessibility. Ultrastructure survey of chromoplast and cell wall morphology in nine carotenoid-containing fruits and vegetables. J. Sci. Food Agric. 92:2594-602
56. Jeffery JL, Turner ND, King SR. 2012b. Carotenoid bioaccessibility from nine raw carotenoid-storing fruits and vegetables using an in vitro model. J. Sci. Food Agric. 92:2603-10
57. Jia JX, Wasan KM. 2008. Effects of monoglycerides on rhodamine 123 accumulation, estradiol 17 beta-Dglucuronide bidirectional transport and MRP2 protein expression within Caco-2 cells. J. Pharm. Pharma. Sci. 11:45-62
58. Jin MJ, Han HK. 2010. Effect of piperine, a major component of black pepper, on the intestinal absorption of fexofenadine and its implication on food-drug interaction. J. Food Sci. 75:H93-96
59. Kang MJ, Cho JY, Shim BH, Kim DK, Lee J. 2009. Bioavailability enhancing activities of natural compounds from medicinal plants. J. Med. Plants Res. 3:1204-11
60. Kenmogne-DomguiaHB, Moisan S, Viau M, Genot C,Meynier A. 2014. The initial characteristics of marine oil emulsions and the composition of the media inflect lipid oxidation during in vitro gastrointestinal digestion. Food Chem. 152:146-54
61. Kiefer C, Sumser E,WernetMF, Von Lintig J. 2002. A class B scavenger receptormediates the cellular uptake of carotenoids in Drosophila. Proc. Natl. Acad. Sci. USA 16:10581-86
62. Kimura O, Ohta C, Koga N, Haraguchi K, Kato Y, Endo T. 2014. Carrier-mediated uptake of nobiletin, a citrus polymethoxyflavonoid, in human intestinal Caco-2 cells. Food Chem. 154:145-50
63. Kindel T, Lee DM, Tso P. 2010. The mechanism of the formation and secretion of chylomicrons. Atheroscler. Suppl. 11:11-16
64. Koga N, Ohta C, Kato Y, Haraguchi K, Endo T, et al. 2011. In vitro metabolism of nobiletin, a polymethoxyflavonoid, by human liver microsomes and cytochrome P450. Xenobiotica 41:927-33
65. Kosinska A, Andlauer W. 2013. Modulation of tight junction integrity by food components. Food Res. Int. 54:951-60
66. Kulling S, Honig D, Metzler M. 2000. Oxidative metabolism of the soy isoflavones daidzein and genistein in humans in vitro and in vivo. J. Agric. Food Chem. 48:4963-72
67. Lambert DJ, Sang S, Yang SC. 2007. Biotransformation of green tea polyphenols and the biological activities of those metabolites. Mol. Pharma. 4(6):819-25
68. Larkin T, Price EW, Astheimer L. 2008. The key importance of soy isoflavone bioavailability to understanding health benefits. Food Sci. Nutr. 48:538-52
69. Larsson K, Cavonius L, Alminger M, Undeland I. 2012. Oxidation of cod liver oil during gastrointestinal in vitro digestion. J. Agric. Food Chem. 60:7556-64
70. Lennernas H, Abrahamsson B, Persson EM, Knutson L. 2007. Oral drug absorption and the biopharmaceutics classification system. J. Drug Deliv. Sci. Technol. 17:237-44
71. Lesser S, Cermak R, Wolffram S. 2004. Bioavailability of quercetin in pigs is influenced by the dietary fat content. J. Nutr. 134:1508-11
72. Li S, Wang H, Guo L, Zhao H, Ho CT. 2014. Chemistry and bioactivity of nobiletin and its metabolites. J. Funct. Foods 6:2-10
73. Liu Y, Hu M. 2002. Absorption and metabolism of flavonoids in the Caco-2 cell culture model and a perused rat intestinal model. Drug Metab. Dispos. 30:370-77
74. Lo CM, Tso P. 2009. Physicochemical basis of the digestion and absorption of triacylglycerol. In Designing Functional Foods: Measuring and Controlling Food Structure Breakdown and Nutrition Absorption, ed. DJ McClements, EA Decker, pp. 94-125. Cambridge, UK: Woodhead Publ.
75. Martinez MN, Amidon GL. 2002. A mechanistic approach to understanding the factors affecting drug absorption: a review of fundamentals. J. Clin. Pharmacol. 42:620-43
76. McClements DJ. 2012. Crystals and crystallization in oil-in-water emulsions: implications for emulsion-based delivery systems. Adv. Colloid Interface Sci. 174:1-30
77. McClements DJ. 2013. Utilizing food effects to overcome challenges in delivery of lipophilic bioactives: structural design of medical and functional foods. Expert Opin. Drug Deliv. 10:1621-32
78. McClements DJ, Decker EA. 2008. Lipids. In Fennema's Food Chemistry, ed. S Damodaran, KL Parkin, OR Fennema, pp. 155-216. Boca Raton: CRC Press. 4th ed.
79. McClements DJ, Decker EA, Park Y, Weiss J. 2009. Structural design principles for delivery of bioactive components in nutraceuticals and functional foods. Crit. Rev. Food Sci. Nutr. 49:577-606
80. McClements DJ, Xiao H. 2014. Excipient foods: designing food matrices that improve the oral bioavailability of pharmaceuticals and nutraceuticals. Food Funct. 5:1320-33
81. McGhie TK,Walton MC. 2007. The bioavailability and absorption of anthocyanins: towards a better understanding. Mol. Nutr. Food Res. 51:702-13
82. Metzler M, Pfeiffer E, Schulz SI, Dempe JS. 2013. Curcumin uptake and metabolism. Biofactors 39:14-20
83. Misaka S, Muller F, FrommMF. 2013. Clinical relevance of drug efflux pumps in the gut. Curr. Opin. Pharmacol. 13:847-52
84. Moelants KRN, Lemmens L, Vandebroeck M, Van Buggenhout S, Van Loey AM, Hendrickx ME. 2012. Relation between particle size and carotenoid bioaccessibility in carrot-and tomato-derived suspensions. J. Agric. Food Chem. 60:11995-2003
85. MonagasM, Urpi-SardaM, Sanchez-Patan F, Llorach R, Garrido I, et al. 2010. Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites. Food Funct. 1:233-53
86. Moreno FJ. 2007. Gastrointestinal digestion of food allergens: effect on their allergenicity. Biomed. Pharmacother. 61:50-60
87. Murakami A, Koshimizu K, Ohigashi H, Kuwahara S, Kukic W, et al. 2002. Characteristic rat tissue accumulation of nobiletin, a chemopreventive polymethoxyflavonoid, in comparison with luteolin. Biofactors 16:73-82
88. Murota K, Shimizu S, Chujo H, Moon JH, Terao J. 2000. Efficiency of absorption and metabolic conversion of quercetin and its glucosides in human intestinal cell line Caco-2. Arch. Biochem. Biophys. 384:391-97
89. Nagao A, Kotake-Nara E, Hase M. 2013. Effects of fats and oils on the bioaccessibility of carotenoids and vitamin E in vegetables. Biosci. Biotechnol. Biochem. 77:1055-60
90. Panozzo A, Lemmens L, Van Loey A, Manzocco L, Nicoli MC, Hendrickx M. 2013. Microstructure and bioaccessibility of different carotenoid species as affected by high pressure homogenisation: a case study on differently coloured tomatoes. Food Chem. 141:4094-100
91. Passamonti S, Vrhovsek U, Mattivi F. 2002. The interaction of anthocyanins with bilitranslocase. Biochem. Biophys. Res. Commun. 296:631-36
92. Patel AR, Velikov KP. 2011. Colloidal delivery systems in foods: a general comparison with oral drug delivery. Lwt-Food Sci. Technol. 44:1958-64
93. Pawar BY, Munjal B, Arora S, Karwa M, Kohli G, et al. 2012. Bioavailability of a lipidic formulation of curcumin in healthy human volunteers. Pharmaceutics 4:517-30
94. PetriN, Tannergren C,Holst B, Mellon FA, Bao YP, et al. 2003. Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejunum in vivo. Drug Metab. Dispos. 31:805-13
95. Planas JM, Alfaras I, Colom H, Juan ME. 2012. The bioavailability and distribution of trans-resveratrol are constrained by ABC transporters. Arch. Biochem. Biophys. 527:67-73
96. Porter CJH, Trevaskis NL, Charman WN. 2007. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat. Rev. Drug Discov. 6:231-48
97. Porter CJH, Wasan KM. 2008. Lipid-based systems for the enhanced delivery of poorly water soluble drugs. Adv. Drug Deliv. Rev. 60:615-16
98. Pouton CW, Porter CJ. 2008. Formulation of lipid-based delivery systems for oral administration: materials, methods and strategies. Adv. Drug Deliv. Rev. 60:625-37
99. Prior RL, Wu X. 2006. Anthocyanins: structural characteristics that result in unique metabolic patterns and biological activities. Free Radic. Res. 40(10):1014-28
100. Qian C, Decker EA, Xiao H, McClements DJ. 2012. Nanoemulsion delivery systems: influence of carrier oil on beta-carotene bioaccessibility. Food Chem. 135:1440-47
101. Reboul E. 2013. Absorption of vitamin A and carotenoids by the enterocyte: focus on transport proteins. Nutrients 5:3563-81
102. Reboul E, Klein A, Bietrix F, Gleize B, Malezet-Desmoulins C, et al. 2006. Scavenger receptor class B type I (SR-BI) is involved in vitamin E transport across the enterocyte. J. Biol. Chem. 281:4739-45
103. Rein MJ, Renouf M, Cruz-Hernandez C, Actis-Goretta L, Thakkar SK, Pinto MD. 2013. Bioavailability of bioactive food compounds: a challenging journey to bioefficacy. Br. J. Clin. Pharmacol. 75:588-602
104. Rigotti A, Miettinen HE, Krieger M. 2003. The role of the high-density lipoprotein receptor SR-BI in the lipid metabolism of endocrine and other tissues. Endocr. Rev. 24:357-87
105. Rimbach G, Pallauf J, Moehring J, Kraemer K, Minihane AM. 2008. Effect of dietary phytate and microbial phytase on mineral and trace element bioavailability-a literature review. Curr. Top. Nutraceutical Res. 6:131-44
106. Rosenthal R,Heydt MS, Amasheh M, Stein C, Fromm M, Amasheh S. 2012. Analysis of absorption enhancers in epithelial cell models. Ann. N.Y. Acad Sci. 1258:86-92
107. Rothwell AJ, Day JA, Morgan RAA. 2005. Experimental determination of octanol-water partition coefficients of quercetin and related flavonoids. J. Agric. Food Chem. 53:4355-60
108. Rozner S, ShalevDE, Shames AI, OttavianiMF, Aserin A,Garti N. 2010. Do food microemulsions and dietary mixed micelles interact Colloids Surfaces B 77:22-30
109. Rupp C, Steckel H, Muller BW. 2010. Solubilization of poorly water-soluble drugs by mixed micelles based on hydrogenated phosphatidylcholine. Int. J. Pharma. 395:272-80
110. Saaber D, Wollenhaupt S, Baumann K, Reichl S. 2014. Recent progress in tight junction modulation for improving bioavailability. Expert Opin. Drug Discov. 9:367-81
111. Sabolovic N, Humbert AC, Radominska-Pandya A, Magdalou J. 2006. Resveratrol is efficiently glucuronidated by UDP-glucuronosyltransferases in the human gastrointestinal tract and inCaco-2 cells. Biopharma. Drug Dispos. 27:181-89
112. Salvia-Trujillo L, Qian C, Martin-Belloso O, McClements DJ. 2013a. Influence of particle size on lipid digestion and beta-carotene bioaccessibility in emulsions and nanoemulsions. Food Chem. 141:1472-80
113. Salvia-Trujillo L, Qian C, Martin-Belloso O, McClements DJ. 2013b. Modulating beta-carotene bioaccessibility by controlling oil composition and concentration in edible nanoemulsions. Food Chem. 139:878-84
114. Seki T, Harada S, Hosoya O, Morimoto K, Juni K. 2008. Evaluation of the establishment of a tight junction in Caco-2 cell monolayers using a pore permeation model involving two different sizes. Biol. Pharma. Bull. 31:163-66
115. Shimizu M. 2010. Interaction between food substances and the intestinal epithelium. Biosci. Biotechnol. Biochem. 74:232-41
116. Stevenson DE, Scheepens A, Hurst RD. 2009. Bioavailability and metabolism of dietary flavonoids-much known-much more to discover. In Flavonoids: Biosynthesis, Biological Effects and Dietary Sources, ed. RB Keller, pp. 1-52. Hauppauge: Nova Sci. Publ.
117. TagashiraT, ChoshiT,Hibino S, Kamishikiryou J, Sugihara N. 2012. Influence of gallate and pyrogallolmoieties on the intestinal absorption of epicatechin and epicatechin gallate. J. Food Sci. 77(10):H208-15
118. Tarvainen M, Phuphusit A, Suomela JP, Kuksis A, Kallio H. 2012. Effects of antioxidants on rapeseed oil oxidation in an artificial digestion model analyzed by UHPLC-ESI-MS. J. Agric. Food Chem. 60:3564-79
119. Tso P, Nauli A, Lo CM. 2004. Enterocyte fatty acid uptake and intestinal fatty acid-binding protein. Biochem. Soc. Trans. 32:75-78
120. Tsutsumi K, Li SK, Hymas RV, Teng CL, Tillman LG, et al. 2008. Systematic studies on the paracellular permeation of model permeants and oligonucleotides in the rat small intestine with chenodeoxycholate as enhancer. J. Pharma. Sci. 97:350-67
121. Tydeman EA, Parker ML, Faulks RM, Cross KL, Fillery-Travis A, et al. 2010. Effect of carrot (Daucus carota)microstructure on carotene bioaccessibility in the upper gastrointestinal tract. 2. In vivo digestions. J. Agric. Food Chem. 58:9855-60
122. Vaidyanathan BJ,Walle T. 2001. Transport and metabolism of the tea flavonoid epicatechin by the human intestinal cell line Caco-2. Pharma. Res. 18(10):1420-25
123. van Bennekum A, Werder M, Thuahnai ST, Han CH, Duong P, et al. 2005. Class B scavenger receptormediated intestinal absorption of dietary beta-carotene and cholesterol. Biochemistry 44:4517-25
124. van het Hof KH, West CE,Weststrate JA, Hautvast J. 2000. Dietary factors that affect the bioavailability of carotenoids. J. Nutr. 132:503-6
125. Varum FJO, Hatton GB, Basit AW. 2013. Food, physiology and drug delivery. Int. J. Pharma. 457:446-60
126. Vaz-da-SilvaM, Loureiro AI, Falcao A, Nunes T, Rocha JF, et al. 2008. Effect of food on the pharmacokinetic profile of transresveratrol. Int. J. Clin. Pharmacol. Ther. 46:564-70
127. Velderrain-Rodriguez GR, Palafox-Carlos H, Wall-Medrano A, Ayala-Zavala JF, Chen CYO, et al. 2014. Phenolic compounds: their journey after intake. Food Funct. 5:189-97
128. Velikov KP, Pelan E. 2008. Colloidal delivery systems for micronutrients and nutraceuticals. Soft Matter 4:1964-80
129. Vermeulen M, Klopping-Ketelaars WAAI, Berg VDR, Vaes HJW. 2008. Bioavailability and kinetics of sulforaphane in humans after consumption of cooked versus raw broccoli. J. Agric. Food Chem. 56:10505-9
130. Vitaglione P, Sforza S, Galaverna G, Ghidini C, Caporaso N, et al. 2005. Bioavailability of trans-resveratrol from red wine in humans. Mol. Nutr. Food Res. 49:495-504
131. Wahlang B, Pawar BY, Bansal KA. 2011. Identification of permeability-related hurdles in oral delivery of curcumin using the Caco-2 cell model. Eur. J. Pharma. Biopharma. 77:275-82
132. Walle T. 2011. Bioavailability of resveratrol. Ann. N. Y. Acad. Sci. 1215(2011):9-15
133. Wickham M, Faulks R, Mills C. 2009. In vitro digestion methods for assessing the effect of food structure on allergen breakdown. Mol. Nutr. Food Res. 53:952-58
134. Wildman REC, Kelley M. 2007. Nutraceuticals and functional foods. In Handbook of Nutraceuticals and Functional Foods, ed. RECWildman, pp. 1-22. Boco Raton, FL: CRC Press. 2nd ed.
135. Williams HD, Trevaskis NL, Charman SA, Shanker RM, Charman WN, et al. 2013. Strategies to address low drug solubility in discovery and development. Pharmacol. Rev. 65:315-499
136. WuCY, Benet LZ. 2005. Predicting drug disposition via application of BCS: transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharma. Res. 22:11-23
137. Wydro P, Krajewska B, Hac-Wydro K. 2007. Chitosan as a lipid binder: a Langmuir monolayer study of chitosan-lipid interactions. Biomacromolecules 8:2611-17
138. Xiao H, Zheng JK, Song MY, Zhong ZM,Wang MQ. 2012. The metabolism of polymethoxyflavone and its implication in colon cancer inhibition. FASEB J. 26:124.5
139. Xu LL, He YQ, Guo X, Lu YH,Wang CH. 2011. Identification of metabolites of nobiletin in rats using ultraperformance liquid chromatography coupled with triple-quadrupole mass spectrometry. Acta Pharma. Sinica 46(12):1483-87
140. Yanez JA, Wang SWJ, Knemeyer IW, Wirth MA, Alton KB. 2011. Intestinal lymphatic transport for drug delivery. Adv. Drug Deliv. Rev. 63:923-42
141. YaoM, Chen J, Zheng J, Song M, McClements JD, Xiao H. 2013. Enhanced lymphatic transport of bioactive lipids: cell culture study of polymethoxyflavone incorporation into chylomicrons. Food Funct. 4:1662-67
142. Yeap YY, Trevaskis NL,Quach T, Tso P,CharmanWN,PorterCJH. 2013. Intestinal bile secretion promotes drug absorption from lipid colloidal phases via induction of supersaturation. Mol. Pharma. 10:1874-89
143. Yeum KJ, Russell RM. 2002. Carotenoid bioavailability and bioconversion. Annu. Rev. Nutr. 22:483-504
144. Yonekura L, Nagao A. 2007. Intestinal absorption of dietary carotenoids. Mol. Nutr. Food Res. 51:107-15
145. Yonekura L, Nagao A. 2009. Soluble fibers inhibit carotenoid micellization in vitro and uptake by Caco-2 cells. Biosci. Biotechnol. Biochem. 73:196-99