A Comprehensive Review of Nanoparticles for Oral Delivery in Food: Biological Fate, Evaluation Models, and Gut Microbiota Influences

Literature Cited

1. Abuznait AH, Qosa H, O'Connell ND, Akbarian-Tefaghi J, Sylvester PW et al. 2011. Induction of expression and functional activity of P-glycoprotein efflux transporter by bioactive plant natural products. Food Chem. Toxicol. 49:112765–72
   [Google Scholar]
2. Ahadian S, Finbloom JA, Mofidfar M, Diltemiz SE, Nasrollahi F et al. 2020. Micro and nanoscale technologies in oral drug delivery. Adv. Drug Deliv. Rev. 157:37–62
   [Google Scholar]
3. Ahmad N, Alam MA, Ahmad R, Umar S, Jalees Ahmad F. 2018. Improvement of oral efficacy of irinotecan through biodegradable polymeric nanoparticles through in vitro and in vivo investigations. J. Microencapsul. 35:4327–43
   [Google Scholar]
4. Ahn J, Ko J, Lee S, Yu J, Kim Y, Jeon NL. 2018. Microfluidics in nanoparticle drug delivery; from synthesis to pre-clinical screening. Adv. Drug Deliv. Rev. 128:29–53
   [Google Scholar]
5. Al Rubeaan K, Rafiullah M, Jayavanth S 2016. Oral insulin delivery systems using chitosan-based formulation: a review. Expert Opin. Drug Deliv. 13:2223–37
   [Google Scholar]
6. Albert-Bayo M, Paracuellos I, González-Castro AM, Rodríguez-Urrutia A, Rodríguez-Lagunas MJ et al. 2019. Intestinal mucosal mast cells: key modulators of barrier function and homeostasis. Cells 8:2135
   [Google Scholar]
7. Almansour M, Alarifi S, Jarrar B. 2018. In vivo investigation on the chronic hepatotoxicity induced by intraperitoneal administration of 10-nm silicon dioxide nanoparticles. Int. J. Nanomed. 13:2685–96
   [Google Scholar]
8. Anby MU, Nguyen TH, Yeap YY, Feeney OM, Williams HD et al. 2014. An in vitro digestion test that reflects rat intestinal conditions to probe the importance of formulation digestion versus first pass metabolism in danazol bioavailability from lipid based formulations. Mol. Pharm. 11:114069–83
   [Google Scholar]
9. Araujo F, Pereira C, Costa J, Barrias C, Granja PL, Sarmento B. 2016. In vitro M-like cells genesis through a tissue-engineered triple-culture intestinal model. J. Biomed. Mater. Res. B 104:4782–88
   [Google Scholar]
10. Arms L, Smith DW, Flynn J, Palmer W, Martin A et al. 2018. Advantages and limitations of current techniques for analyzing the biodistribution of nanoparticles. Front. Pharmacol. 9:802
    [Google Scholar]
11. Arranz E, Corredig M, Guri A. 2016. Designing food delivery systems: challenges related to the in vitro methods employed to determine the fate of bioactives in the gut. Food Funct. 7:83319–36
    [Google Scholar]
12. Arshad R, Gulshad L, Haq IU, Farooq MA, Al-Farga A, Siddique R et al. 2021. Nanotechnology: a novel tool to enhance the bioavailability of micronutrients. Food Sci. Nutr. 9:63354–61
    [Google Scholar]
13. Artursson P, Palm K, Luthman K. 2001. Caco-2 monolayers in experimental and theoretical predictions of drug transport. Adv. Drug Deliv. Rev. 46:1–327–43
    [Google Scholar]
14. Bannunah AM, Vllasaliu D, Lord J, Stolnik S. 2014. Mechanisms of nanoparticle internalization and transport across an intestinal epithelial cell model: effect of size and surface charge. Mol. Pharm. 11:124363–73
    [Google Scholar]
15. Bao C, Jiang P, Chai J, Jiang Y, Li D et al. 2019. The delivery of sensitive food bioactive ingredients: absorption mechanisms, influencing factors, encapsulation techniques and evaluation models. Food Res. Int. 120:130–40
    [Google Scholar]
16. Béduneau A, Tempesta C, Fimbel S, Pellequer Y, Jannin V et al. 2014. A tunable Caco-2/HT29-MTX co-culture model mimicking variable permeabilities of the human intestine obtained by an original seeding procedure. Eur. J. Pharm. Biopharm. 87:2290–98
    [Google Scholar]
17. Beguin P, Errachid A, Larondelle Y, Schneider YJ. 2013. Effect of polyunsaturated fatty acids on tight junctions in a model of the human intestinal epithelium under normal and inflammatory conditions. Food Funct. 4:6923–31
    [Google Scholar]
18. Behrens I, Stenberg P, Artursson P, Kissel T. 2001. Transport of lipophilic drug molecules in a new mucus-secreting cell culture model based on HT29-MTX cells. Pharm. Res. 18:81138–45
    [Google Scholar]
19. Beig A, Miller JM, Dahan A. 2012. Accounting for the solubility–permeability interplay in oral formulation development for poor water solubility drugs: the effect of PEG-400 on carbamazepine absorption. Eur. J. Pharm. Biopharm. 81:2386–91
    [Google Scholar]
20. Beloqui A, des Rieux A, Préat V. 2016. Mechanisms of transport of polymeric and lipidic nanoparticles across the intestinal barrier. Adv. Drug Deliv. Rev. 106:242–55
    [Google Scholar]
21. Bergin IL, Witzmann FA. 2013. Nanoparticle toxicity by the gastrointestinal route: evidence and knowledge gaps. Int. J. Biomed. Nanosci. Nanotechnol. 3:1–2163–210
    [Google Scholar]
22. Bermudez-Brito M, Muñoz-Quezada S, Gómez-Llorente C, Matencio E, Romero F, Gil A. 2015. Lactobacillus paracasei CNCM I-4034 and its culture supernatant modulate Salmonella-induced inflammation in a novel transwell co-culture of human intestinal-like dendritic and Caco-2 cells. BMC Microbiol. 15:179
    [Google Scholar]
23. Berthelsen R, Klitgaard M, Rades T, Müllertz A. 2019. In vitro digestion models to evaluate lipid based drug delivery systems; present status and current trends. Adv. Drug Deliv. Rev. 142:35–49
    [Google Scholar]
24. Blanco E, Shen H, Ferrari M. 2015. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 33:9941–51
    [Google Scholar]
25. Boegh M, Baldursdóttir SG, Müllertz A, Nielsen HM. 2014. Property profiling of biosimilar mucus in a novel mucus-containing in vitro model for assessment of intestinal drug absorption. Eur. J. Pharm. Biopharm. 87:2227–35
    [Google Scholar]
26. Böhmert L, Girod M, Hansen U, Maul R, Knappe P et al. 2014. Analytically monitored digestion of silver nanoparticles and their toxicity on human intestinal cells. Nanotoxicology 8:6631–42
    [Google Scholar]
27. Borcherding J, Baltrusaitis J, Chen H, Stebounova L, Wu CM et al. 2014. Iron oxide nanoparticles induce Pseudomonas aeruginosa growth, induce biofilm formation, and inhibit antimicrobial peptide function. Environ. Sci. Nano 1:2123–32
    [Google Scholar]
28. Borel T, Sabliov C. 2014. Nanodelivery of bioactive components for food applications: types of delivery systems, properties, and their effect on ADME profiles and toxicity of nanoparticles. Annu. Rev. Food Sci. Technol. 5:197–213
    [Google Scholar]
29. Bothiraja C, Pawar A, Deshpande G. 2016. Ex-vivo absorption study of a nanoparticle based novel drug delivery system of vitamin D₃ (Arachitol Nano™) using everted intestinal sac technique. J. Pharm. Investig. 46:5425–32
    [Google Scholar]
30. Burton PS, Conradi RA, Hilgers AR. 1991. (B) Mechanisms of peptide and protein absorption: (2) transcellular mechanism of peptide and protein absorption: passive aspects. Adv. Drug Deliv. Rev. 7:3365–85
    [Google Scholar]
31. Butler M, Ng CY, van Heel DA, Lombardi G, Lechler R et al. 2006. Modulation of dendritic cell phenotype and function in an in vitro model of the intestinal epithelium. Eur. J. Immunol. 36:4864–74
    [Google Scholar]
32. Cao P, Xu ZP, Li L. 2022. Tailoring functional nanoparticles for oral vaccine delivery: recent advances and future perspectives. Compos. B Eng. 236:109826
    [Google Scholar]
33. Carrière F. 2016. Impact of gastrointestinal lipolysis on oral lipid-based formulations and bioavailability of lipophilic drugs. Biochimie 125:297–305
    [Google Scholar]
34. Cattani VB, Fiel LA, Jäger A, Jäger E, Colomé LM et al. 2010. Lipid-core nanocapsules restrained the indomethacin ethyl ester hydrolysis in the gastrointestinal lumen and wall acting as mucoadhesive reservoirs. Eur. J. Pharm. Sci. 39:1–3116–24
    [Google Scholar]
35. Chang C, Wang T, Hu Q, Zhou M, Xue J, Luo Y. 2017. Pectin coating improves physicochemical properties of caseinate/zein nanoparticles as oral delivery vehicles for curcumin. Food Hydrocoll. 70:143–51
    [Google Scholar]
36. Chen CC, Tsai TH, Huang ZR, Fang JY. 2010. Effects of lipophilic emulsifiers on the oral administration of lovastatin from nanostructured lipid carriers: physicochemical characterization and pharmacokinetics. Eur. J. Pharm. Biopharm. 74:3474–82
    [Google Scholar]
37. Chen H, Yao Y. 2017. Phytoglycogen to increase lutein solubility and its permeation through Caco-2 monolayer. Food Res. Int. 97:258–64
    [Google Scholar]
38. Chen Y, Xue J, Wang T, Hu Q, Luo Y. 2020. Carboxymethylation of phytoglycogen and its interactions with caseinate for the preparation of nanocomplex. Food Hydrocoll. 100:105390
    [Google Scholar]
39. Chivere VT, Kondiah PP, Choonara YE, Pillay V. 2020. Nanotechnology-based biopolymeric oral delivery platforms for advanced cancer treatment. Cancers 12:2522
    [Google Scholar]
40. Chou DB, Frismantas V, Milton Y, David R, Pop-Damkov P et al. 2020. On-chip recapitulation of clinical bone marrow toxicities and patient-specific pathophysiology. Nat. Biomed. Eng. 4:4394–406
    [Google Scholar]
41. Christophersen PC, Christiansen ML, Holm R, Kristensen J, Jacobsen J et al. 2014. Fed and fasted state gastro-intestinal in vitro lipolysis: in vitro in vivo relations of a conventional tablet, a SNEDDS and a solidified SNEDDS. Eur. J. Pharm. Sci. 57:232–39
    [Google Scholar]
42. Ciappellano SG, Tedesco E, Venturini M, Benetti F. 2016. In vitro toxicity assessment of oral nanocarriers. Adv. Drug Deliv. Rev. 106:381–401
    [Google Scholar]
43. Collins J, Auchtung JM, Schaefer L, Eaton KA, Britton RA. 2015. Humanized microbiota mice as a model of recurrent Clostridium difficile disease. Microbiome 3:135
    [Google Scholar]
44. Cone RA. 2009. Barrier properties of mucus. Adv. Drug Deliv. Rev. 61:275–85
    [Google Scholar]
45. Dahan A, Hoffman A. 2007. The effect of different lipid based formulations on the oral absorption of lipophilic drugs: the ability of in vitro lipolysis and consecutive ex vivo intestinal permeability data to predict in vivo bioavailability in rats. Eur. J. Pharm. Biopharm. 67:196–105
    [Google Scholar]
46. Dahiya DK, Renuka PM, Shandilya UK, Dhewa T et al. 2017. Gut microbiota modulation and its relationship with obesity using prebiotic fibers and probiotics: a review. Front. Microbiol. 8:563
    [Google Scholar]
47. Dawson M, Krauland E, Wirtz D, Hanes J. 2004. Transport of polymeric nanoparticle gene carriers in gastric mucus. Biotechnol. Prog. 20:3851–57
    [Google Scholar]
48. Dawson M, Wirtz D, Hanes J. 2003. Enhanced viscoelasticity of human cystic fibrotic sputum correlates with increasing microheterogeneity in particle transport. J. Biol. Chem. 278:5050393–401
    [Google Scholar]
49. de Sousa IP, Cattoz B, Wilcox MD, Griffiths PC, Dalgliesh R et al. 2015. Nanoparticles decorated with proteolytic enzymes, a promising strategy to overcome the mucus barrier. Eur. J. Pharm. Biopharm. 97:257–64
    [Google Scholar]
50. Deat E, Blanquet-Diot S, Jarrige JF, Denis S, Beyssac E, Alric M. 2009. Combining the dynamic TNO-gastrointestinal tract system with a Caco-2 cell culture model: application to the assessment of lycopene and α-tocopherol bioavailability from a whole food. J. Agric. Food Chem. 57:2311314–20
    [Google Scholar]
51. Delie F. 1998. Evaluation of nano- and microparticle uptake by the gastrointestinal tract. Adv. Drug Deliv. Rev. 34:2–3221–33
    [Google Scholar]
52. des Rieux A, Fievez V, Théate I, Mast J, Préat V, Schneider YJ. 2007. An improved in vitro model of human intestinal follicle-associated epithelium to study nanoparticle transport by M cells. Eur. J. Pharm. Sci. 30:5380–91
    [Google Scholar]
53. des Rieux A, Ragnarsson EG, Gullberg E, Préat V, Schneider Y-J, Artursson P. 2005. Transport of nanoparticles across an in vitro model of the human intestinal follicle associated epithelium. Eur. J. Pharm. Sci. 25:4–5455–65
    [Google Scholar]
54. Dickinson PA, Rmaileh RA, Ashworth L, Barker RA, Burke WM et al. 2012. An investigation into the utility of a multi-compartmental, dynamic, system of the upper gastrointestinal tract to support formulation development and establish bioequivalence of poorly soluble drugs. AAPS J. 14:2196–205
    [Google Scholar]
55. Ding X, Yu Q, Hou K, Hu X, Wang Y et al. 2020. Indirectly stimulation of DCs by Ganoderma atrum polysaccharide in intestinal-like Caco-2/DCs co-culture model based on RNA-seq. J. Funct. Foods 67:103850
    [Google Scholar]
56. Dos Santos T, Varela J, Lynch I, Salvati A, Dawson KA 2011. Effects of transport inhibitors on the cellular uptake of carboxylated polystyrene nanoparticles in different cell lines. PLOS ONE 6:9e24438
    [Google Scholar]
57. Dünnhaupt S, Kammona O, Waldner C, Kiparissides C, Bernkop-Schnürch A. 2015. Nano-carrier systems: strategies to overcome the mucus gel barrier. Eur. J. Pharm. Biopharm. 96:447–53
    [Google Scholar]
58. Durán-Lobato M, Martín-Banderas L, Lopes R, Gonçalves L, Fernández-Arévalo M, Almeida A. 2016. Lipid nanoparticles as an emerging platform for cannabinoid delivery: physicochemical optimization and biocompatibility. Drug Dev. Ind. Pharm. 42:2190–98
    [Google Scholar]
59. Echegoyen Y, Nerín C. 2013. Nanoparticle release from nano-silver antimicrobial food containers. Food Chem. Toxicol. 62:16–22
    [Google Scholar]
60. Ekert JE, Johnson K, Strake B, Pardinas J, Jarantow S et al. 2014. Three-dimensional lung tumor microenvironment modulates therapeutic compound responsiveness in vitro: implication for drug development. PLOS ONE 9:3e92248
    [Google Scholar]
61. El Badawy AM, Silva RG, Morris B, Scheckel KG, Suidan MT, Tolaymat TM 2011. Surface charge-dependent toxicity of silver nanoparticles. Environ. Sci. Technol. 45:1283–87
    [Google Scholar]
62. Esch MB, Mahler GJ, Stokol T, Shuler ML. 2014. Body-on-a-chip simulation with gastrointestinal tract and liver tissues suggests that ingested nanoparticles have the potential to cause liver injury. Lab Chip 14:163081–92
    [Google Scholar]
63. Etheridge ML, Campbell SA, Erdman AG, Haynes CL, Wolf SM, McCullough J. 2013. The big picture on nanomedicine: the state of investigational and approved nanomedicine products. Nanomedicine 9:11–14
    [Google Scholar]
64. Fairstein M, Swissa R, Dahan A. 2013. Regional-dependent intestinal permeability and BCS classification: elucidation of pH-related complexity in rats using pseudoephedrine. AAPS J. 15:2589–97
    [Google Scholar]
65. Fatouros DG, Deen GR, Arleth L, Bergenstahl B, Nielsen FS et al. 2007. Structural development of self nano emulsifying drug delivery systems (SNEDDS) during in vitro lipid digestion monitored by small-angle X-ray scattering. Pharm. Res. 24:101844–53
    [Google Scholar]
66. Fredrikzon B, Olivecrona T. 1978. Decrease of lipase and esterase activities in intestinal contents of newborn infants during test meals. Pediatr. Res. 12:5631–34
    [Google Scholar]
67. Frontela-Saseta C, López-Nicolás R, González-Bermúdez CA, Martínez-Graciá C, Ros-Berruezo G. 2013. Anti-inflammatory properties of fruit juices enriched with pine bark extract in an in vitro model of inflamed human intestinal epithelium: the effect of gastrointestinal digestion. Food Chem. Toxicol. 53:94–99
    [Google Scholar]
68. Gerloff K, Pereira DI, Faria N, Boots AW, Kolling J et al. 2013. Influence of simulated gastrointestinal conditions on particle-induced cytotoxicity and interleukin-8 regulation in differentiated and undifferentiated Caco-2 cells. Nanotoxicology 7:4353–66
    [Google Scholar]
69. Ghadimi D, Helwig U, Schrezenmeir J, Heller KJ, de Vrese M. 2012. Epigenetic imprinting by commensal probiotics inhibits the IL-23/IL-17 axis in an in vitro model of the intestinal mucosal immune system. J. Leukoc. Biol. 92:4895–911
    [Google Scholar]
70. Giampetruzzi L, Barca A, De Pascali C, Capone S, Verri T et al. 2018. Human organ-on-a-chip: around the intestine bends. . In Convegno Nazionale Sensori181–88 Cham, Switz: Springer
    [Google Scholar]
71. Goldberg M, Gomez-Orellana I. 2003. Challenges for the oral delivery of macromolecules. Nat. Rev. Drug Discov. 2:4289–95
    [Google Scholar]
72. Guan L, Liu J, Yu H, Tian H, Wu G et al. 2019. Water-dispersible astaxanthin-rich nanopowder: preparation, oral safety and antioxidant activity in vivo. Food Funct. 10:31386–97
    [Google Scholar]
73. Guerra A, Etienne-Mesmin L, Livrelli V, Denis S, Blanquet-Diot S, Alric M. 2012. Relevance and challenges in modeling human gastric and small intestinal digestion. Trends Biotechnol. 30:11591–600
    [Google Scholar]
74. Guimarães M, Statelova M, Holm R, Reppas C, Symilllides M et al. 2019. Biopharmaceutical considerations in paediatrics with a view to the evaluation of orally administered drug products—a PEARRL review. J. Pharm. Pharmacol. 71:4603–42
    [Google Scholar]
75. Gullberg E, Keita ÅV, Sa'ad YS, Andersson M, Caldwell KD et al. 2006. Identification of cell adhesion molecules in the human follicle-associated epithelium that improve nanoparticle uptake into the Peyer's patches. J. Pharmacol. Exp. Ther. 319:2632–39
    [Google Scholar]
76. Gullberg E, Leonard M, Karlsson J, Hopkins AM, Brayden D et al. 2000. Expression of specific markers and particle transport in a new human intestinal M-cell model. Biochem. Biophys. Res. Commun. 279:3808–13
    [Google Scholar]
77. Hendrickson OD, Klochkov SG, Novikova OV, Bravova IM, Shevtsova EF et al. 2016. Toxicity of nanosilver in intragastric studies: biodistribution and metabolic effects. Toxicol. Lett. 241:184–92
    [Google Scholar]
78. Hu Q, Bae M, Fleming E, Lee JY, Luo Y 2019. Biocompatible polymeric nanoparticles with exceptional gastrointestinal stability as oral delivery vehicles for lipophilic bioactives. Food Hydrocoll. 89:386–95
    [Google Scholar]
79. Hu Q, Hu S, Fleming E, Lee J-Y, Luo Y 2020. Chitosan-caseinate-dextran ternary complex nanoparticles for potential oral delivery of astaxanthin with significantly improved bioactivity. Int. J. Biol. Macromol. 151:747–56
    [Google Scholar]
80. Hu Q, Lu Y, Luo Y. 2021. Recent advances in dextran-based drug delivery systems: from fabrication strategies to applications. . Carbohydr. Polym. 264:117999
    [Google Scholar]
81. Hutchinson M, Mallatt J, Marieb EN, Wilhelm PB. 2007. A Brief Atlas of the Human Body London: Pearson
82. Jørgensen SDS, Al Sawaf M, Graeser K, Mu H, Müllertz A, Rades T 2018. The ability of two in vitro lipolysis models reflecting the human and rat gastro-intestinal conditions to predict the in vivo performance of SNEDDS dosing regimens. Eur. J. Pharm. Biopharm. 124:116–24
    [Google Scholar]
83. Kämpfer AA, Urbán P, Gioria S, Kanase N, Stone V, Kinsner-Ovaskainen A. 2017. Development of an in vitro co-culture model to mimic the human intestine in healthy and diseased state. Toxicol. Vitro 45:31–43
    [Google Scholar]
84. Kämpfer AA, Urbán P, La Spina R, Jiménez IO, Kanase N et al. 2020. Ongoing inflammation enhances the toxicity of engineered nanomaterials: application of an in vitro co-culture model of the healthy and inflamed intestine. Toxicol. Vitro 63:104738
    [Google Scholar]
85. Kamstrup D, Berthelsen R, Sassene PJ, Selen A, Müllertz A. 2017. In vitro model simulating gastro-intestinal digestion in the pediatric population (neonates and young infants). AAPS PharmSciTech 18:2317–29
    [Google Scholar]
86. Kang YB, Sodunke TR, Lamontagne J, Cirillo J, Rajiv C et al. 2015. Liver sinusoid on a chip: long-term layered co-culture of primary rat hepatocytes and endothelial cells in microfluidic platforms. Biotechnol. Bioeng. 112:122571–82
    [Google Scholar]
87. Kaukonen AM, Boyd BJ, Charman WN, Porter CJ. 2004. Drug solubilization behavior during in vitro digestion of suspension formulations of poorly water-soluble drugs in triglyceride lipids. Pharm. Res. 21:2254–60
    [Google Scholar]
88. Ke Z, Guo H, Zhu X, Jin Y, Huang Y 2015. Efficient peroral delivery of insulin via vitamin B12 modified trimethyl chitosan nanoparticles. J. Pharm. Pharm. Sci. 18:2155–70
    [Google Scholar]
89. Keiper A. 2003. The nanotechnology revolution. New Atlantis 2:17–34
    [Google Scholar]
90. Kernéis S, Bogdanova A, Kraehenbuhl JP, Pringault E. 1997. Conversion by Peyer's patch lymphocytes of human enterocytes into M cells that transport bacteria. Science 277:5328949–52
    [Google Scholar]
91. Kim HJ, Huh D, Hamilton G, Ingber DE. 2012. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab Chip 12:122165–74
    [Google Scholar]
92. Kim HJ, Ingber DE. 2013. Gut-on-a-chip microenvironment induces human intestinal cells to undergo villus differentiation. Integr. Biol. 5:91130–40
    [Google Scholar]
93. Kim HJ, Li H, Collins JJ, Ingber DE. 2016. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. PNAS 113:1E7–E15
    [Google Scholar]
94. Kimura H, Yamamoto T, Sakai H, Sakai Y, Fujii T. 2008. An integrated microfluidic system for long-term perfusion culture and on-line monitoring of intestinal tissue models. Lab Chip 8:5741–46
    [Google Scholar]
95. Klitgaard M, Sassene PJ, Selen A, Müllertz A, Berthelsen R. 2017. Studying furosemide solubilization using an in vitro model simulating gastrointestinal digestion and drug solubilization in neonates and young infants. Eur. J. Pharm. Sci. 109:191–99
    [Google Scholar]
96. Kucharzik T, Lügering N, Rautenberg K, Lügering A, Schmidt M et al. 2000. Role of M cells in intestinal barrier function. Ann. N. Y. Acad. Sci. 915:1171–83
    [Google Scholar]
97. Lamichhane S, Yde CC, Forssten S, Ouwehand AC, Saarinen M et al. 2014. Impact of dietary polydextrose fiber on the human gut metabolome. J. Agric. Food Chem. 62:409944–51
    [Google Scholar]
98. Langguth P, Bohner V, Heizmann J, Merkle H, Wolffram S et al. 1997. The challenge of proteolytic enzymes in intestinal peptide delivery. J. Control. Release 46:1–239–57
    [Google Scholar]
99. Le Feunteun S, Al-Razaz A, Dekker M, George E, Laroche B, van Aken G 2021. Physiologically based modeling of food digestion and intestinal microbiota: state of the art and future challenges. An INFOGEST review. Annu. Rev. Food Sci. Technol. 12:149–67
    [Google Scholar]
100. Lennernäs H, Palm K, Fagerholm U, Artursson P. 1996. Comparison between active and passive drug transport in human intestinal epithelial (Caco-2) cells in vitro and human jejunum in vivo. Int. J. Pharm. 127:1103–7
     [Google Scholar]
101. Leonard F, Collnot EM, Lehr CM. 2010. A three-dimensional coculture of enterocytes, monocytes and dendritic cells to model inflamed intestinal mucosa in vitro. Mol. Pharm. 7:62103–19
     [Google Scholar]
102. Li C, Fu R, Yu C, Li Z, Guan H et al. 2013. Silver nanoparticle/chitosan oligosaccharide/poly (vinyl alcohol) nanofibers as wound dressings: a preclinical study. Int. J. Nanomed. 8:4131–45
     [Google Scholar]
103. Liu J, Leng P, Liu Y. 2021. Oral drug delivery with nanoparticles into the gastrointestinal mucosa. Fundam. Clin. Pharmacol. 35:186–96
     [Google Scholar]
104. Liu X, Zhang B, Sohal IS, Bello D, Chen H. 2019. Is “nano safe to eat or not”? A review of the state-of-the art in soft engineered nanoparticle (sENP) formulation and delivery in foods. Adv. Food Nutr. Res. 88:299–335
     [Google Scholar]
105. Lowrence RC, Subramaniapillai SG, Ulaganathan V, Nagarajan S. 2019. Tackling drug resistance with efflux pump inhibitors: from bacteria to cancerous cells. . Crit. Rev. Microbiol. 45:3334–53
     [Google Scholar]
106. Lozoya-Agullo I, Araújo F, González-Álvarez I, Merino-Sanjuán M, González-Álvarez M et al. 2017a. Usefulness of Caco-2/HT29-MTX and Caco-2/HT29-MTX/Raji B coculture models to predict intestinal and colonic permeability compared to Caco-2 monoculture. Mol. Pharm. 14:41264–70
     [Google Scholar]
107. Lozoya-Agullo I, González-Álvarez I, González-Álvarez M, Merino-Sanjuán M, Bermejo M. 2015. In situ perfusion model in rat colon for drug absorption studies: comparison with small intestine and Caco-2 cell model. J. Pharm. Sci. 104:93136–45
     [Google Scholar]
108. Lozoya-Agullo I, Zur M, Fine-Shamir N, Markovic M, Cohen Y et al. 2017b. Investigating drug absorption from the colon: single-pass versus Doluisio approaches to in-situ rat large-intestinal perfusion. Int. J. Pharm. 527:1–2135–41
     [Google Scholar]
109. Lundquist P, Artursson P. 2016. Oral absorption of peptides and nanoparticles across the human intestine: opportunities, limitations and studies in human tissues. Adv. Drug Deliv. Rev. 106:256–76
     [Google Scholar]
110. Luo Y. 2020. Food colloids binary and ternary nanocomplexes: innovations and discoveries. Colloids Surf. B 196:111309
     [Google Scholar]
111. Luo Y, Wang Q, Zhang Y. 2020. Biopolymer-based nanotechnology approaches to deliver bioactive compounds for food applications: a perspective on the past, present, and future. J. Agric. Food Chem. 68:4612993–3000
     [Google Scholar]
112. Ma Y, Adibnia V, Mitrache M, Halimi I, Walker GC, Kumacheva E. 2022. Stimulus-responsive nanoconjugates derived from phytoglycogen nanoparticles. Biomacromolecules 23:51928–37
     [Google Scholar]
113. Ma Y, He H, Xia F, Li Y, Lu Y et al. 2017. In vivo fate of lipid-silybin conjugate nanoparticles: implications on enhanced oral bioavailability. Nanomedicine 13:82643–54
     [Google Scholar]
114. Madan JR, Ansari IN, Dua K, Awasthi R. 2020. Formulation and in vitro evaluation of casein nanoparticles as carrier for celecoxib. Adv. Pharm. Bull. 10:3408–17
     [Google Scholar]
115. Malekjani N, Jafari SM. 2021. Modeling the release of food bioactive ingredients from carriers/nanocarriers by the empirical, semiempirical, and mechanistic models. Compr. Rev. Food Sci. Food Saf. 20:13–47
     [Google Scholar]
116. Masiiwa WL, Gadaga LL. 2018. Intestinal permeability of artesunate-loaded solid lipid nanoparticles using the everted gut method. J. Drug Deliv. 2018:3021738
     [Google Scholar]
117. McClements DJ. 2013. Edible lipid nanoparticles: digestion, absorption, and potential toxicity. Prog. Lipid Res. 52:4409–23
     [Google Scholar]
118. McClements DJ, Xiao H. 2017. Is nano safe in foods? Establishing the factors impacting the gastrointestinal fate and toxicity of organic and inorganic food-grade nanoparticles. NPJ Sci. Food 1:6
     [Google Scholar]
119. Mercuri A, Passalacqua A, Wickham MS, Faulks RM, Craig DQ, Barker SA. 2011. The effect of composition and gastric conditions on the self-emulsification process of ibuprofen-loaded self-emulsifying drug delivery systems: a microscopic and dynamic gastric model study. Pharm. Res. 28:71540–51
     [Google Scholar]
120. Minekus M, Marteau P, Havenaar R. 1995. Multicompartmental dynamic computer-controlled model simulating the stomach and small intestine. Altern. Lab. Anim. 23:2197–209
     [Google Scholar]
121. Mitchell MJ, Billingsley MM, Haley RM, Wechsler ME, Peppas NA, Langer R. 2021. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov. 20:2101–24
     [Google Scholar]
122. Molly K, Woestyne MV, Verstraete W. 1993. Development of a 5-step multi-chamber reactor as a simulation of the human intestinal microbial ecosystem. Appl. Microbiol. Biotechnol. 39:2254–58
     [Google Scholar]
123. Monda V, Villano I, Messina A, Valenzano A, Esposito T et al. 2017. Exercise modifies the gut microbiota with positive health effects. Oxidative Med. Cell. Longev. 2017:3831972
     [Google Scholar]
124. Mosgaard MD, Sassene P, Mu H, Rades T, Müllertz A. 2015. Development of a high-throughput in vitro intestinal lipolysis model for rapid screening of lipid-based drug delivery systems. Eur. J. Pharm. Biopharm. 94:493–500
     [Google Scholar]
125. Narciso L, Coppola L, Lori G, Andreoli C, Zjino A et al. 2020. Genotoxicity, biodistribution and toxic effects of silver nanoparticles after in vivo acute oral administration. NanoImpact 18:100221
     [Google Scholar]
126. Ndlovu N, Mayaya T, Muitire C, Munyengwa N. 2020. Nanotechnology applications in crop production and food systems. Int. J. Plant Breed. Crop Sci. 7:1624–34
     [Google Scholar]
127. Nielsen DSG, Fredborg M, Andersen V, Purup S. 2017. Administration of protein kinase D1 induces a protective effect on lipopolysaccharide-induced intestinal inflammation in a co-culture model of intestinal epithelial Caco-2 cells and RAW264.7 macrophage cells. Int. J. Inflamm. 2017:9273640
     [Google Scholar]
128. Olbrich C, Müller R. 1999. Enzymatic degradation of SLN-effect of surfactant and surfactant mixtures. Int. J. Pharm. 180:131–39
     [Google Scholar]
129. Pan J, Lei S, Chang L, Wan D 2019. Smart pH-responsive nanoparticles in a model tumor microenvironment for enhanced cellular uptake. J. Mater. Sci. 54:21692–702
     [Google Scholar]
130. Pawar VK, Meher JG, Singh Y, Chaurasia M, Reddy BS, Chourasia MK. 2014. Targeting of gastrointestinal tract for amended delivery of protein/peptide therapeutics: strategies and industrial perspectives. J. Control. Release 196:168–83
     [Google Scholar]
131. Porter CJ, Kaukonen AM, Taillardat-Bertschinger A, Boyd BJ, O'Connor JM et al. 2004. Use of in vitro lipid digestion data to explain the in vivo performance of triglyceride-based oral lipid formulations of poorly water-soluble drugs: studies with halofantrine. J. Pharm. Sci. 93:51110–21
     [Google Scholar]
132. Portune KJ, Beaumont M, Davila AM, Tomé D, Blachier F, Sanz Y. 2016. Gut microbiota role in dietary protein metabolism and health-related outcomes: the two sides of the coin. Trends Food Sci. Technol. 57:213–32
     [Google Scholar]
133. Pugazhendhi A, Edison TNJI, Karuppusamy I, Kathirvel B. 2018. Inorganic nanoparticles: a potential cancer therapy for human welfare. Int. J. Pharm. 539:1–2104–11
     [Google Scholar]
134. Ranaldi G, Ferruzza S, Canali R, Leoni G, Zalewski PD et al. 2013. Intracellular zinc is required for intestinal cell survival signals triggered by the inflammatory cytokine TNFα. J. Nutr. Biochem. 24:6967–76
     [Google Scholar]
135. Ribeiro LN, Alcântara AC, Darder M, Aranda P, Araújo-Moreira FM, Ruiz-Hitzky E. 2014. Pectin-coated chitosan–LDH bionanocomposite beads as potential systems for colon-targeted drug delivery. Int. J. Pharm. 463:11–9
     [Google Scholar]
136. Rigat-Brugarolas L, Elizalde-Torrent A, Bernabeu M, De Niz M, Martin-Jaular L et al. 2014. A functional microengineered model of the human splenon-on-a-chip. Lab Chip 14:101715–24
     [Google Scholar]
137. Rodriguez NJ, Hu Q, Luo Y. 2019. Oxidized dextran as a macromolecular crosslinker stabilizes the zein/caseinate nanocomplex for the potential oral delivery of curcumin. Molecules 24:224061
     [Google Scholar]
138. Rosa PM, Gopalakrishnan N, Ibrahim H, Haug M, Halaas Ø. 2016. The intercell dynamics of T cells and dendritic cells in a lymph node-on-a-chip flow device. Lab Chip 16:193728–40
     [Google Scholar]
139. Schimpel C, Teubl B, Absenger M, Meindl C, Fröhlich E et al. 2014. Development of an advanced intestinal in vitro triple culture permeability model to study transport of nanoparticles. Mol. Pharm. 11:3808–18
     [Google Scholar]
140. Sender R, Fuchs S, Milo R 2016. Revised estimates for the number of human and bacteria cells in the body. PLOS Biol. 14:8e1002533
     [Google Scholar]
141. Shahbazi M-A, Santos HA. 2013. Improving oral absorption via drug-loaded nanocarriers: absorption mechanisms, intestinal models and rational fabrication. Curr. Drug Metab. 14:128–56
     [Google Scholar]
142. Sieber S, Wirth L, Cavak N, Koenigsmark M, Marx U et al. 2018. Bone marrow-on-a-chip: long-term culture of human haematopoietic stem cells in a three-dimensional microfluidic environment. J. Tissue Eng. Regen. Med. 12:2479–89
     [Google Scholar]
143. Singh V, San Yeoh B, Chassaing B, Xiao X, Saha P et al. 2018. Dysregulated microbial fermentation of soluble fiber induces cholestatic liver cancer. Cell 175:3679–94.e622
     [Google Scholar]
144. Sjögren E, Abrahamsson B, Augustijns P, Becker D, Bolger MB et al. 2014. In vivo methods for drug absorption–comparative physiologies, model selection, correlations with in vitro methods (IVIVC), and applications for formulation/API/excipient characterization including food effects. Eur. J. Pharm. Sci. 57:99–151
     [Google Scholar]
145. Sontheimer-Phelps A, Hassell BA, Ingber DE. 2019. Modelling cancer in microfluidic human organs-on-chips. Nat. Rev. Cancer 19:265–81
     [Google Scholar]
146. Speckmann B, Pinto A, Winter M, Förster I, Sies H, Steinbrenner H. 2010. Proinflammatory cytokines down-regulate intestinal selenoprotein P biosynthesis via NOS2 induction. Free Radic. Biol. Med. 49:5777–85
     [Google Scholar]
147. Sriram G, Alberti M, Dancik Y, Wu B, Wu R et al. 2018. Full-thickness human skin-on-chip with enhanced epidermal morphogenesis and barrier function. Mater. Today 21:4326–40
     [Google Scholar]
148. Sung JH, Srinivasan B, Esch MB, McLamb WT, Bernabini C et al. 2014. Using physiologically-based pharmacokinetic-guided “body-on-a-chip” systems to predict mammalian response to drug and chemical exposure. Exp. Biol. Med. 239:91225–39
     [Google Scholar]
149. Susewind J, de Souza Carvalho-Wodarz C, Repnik U, Collnot E-M, Schneider-Daum N et al. 2016. A 3D co-culture of three human cell lines to model the inflamed intestinal mucosa for safety testing of nanomaterials. Nanotoxicology 10:153–62
     [Google Scholar]
150. Swaan PW. 1998. Recent advances in intestinal macromolecular drug delivery via receptor-mediated transport pathways. Pharm. Res. 15:6826–34
     [Google Scholar]
151. Thuenemann EC, Mandalari G, Rich GT, Faulks RM 2015. Dynamic gastric model (DGM). The Impact of Food Bioactives on Health K Verhoeckx, P Cotter, I López-Expósito, C Kleiveland, T Lea et al.47–59 Cham: Springer
     [Google Scholar]
152. Torisawa YS, Mammoto T, Jiang E, Jiang A, Mammoto A et al. 2016. Modeling hematopoiesis and responses to radiation countermeasures in a bone marrow-on-a-chip. Tissue Eng. Part C 22:5509–15
     [Google Scholar]
153. Tyrer P, Foxwell AR, Cripps AW, Apicella MA, Kyd JM. 2006. Microbial pattern recognition receptors mediate M-cell uptake of a gram-negative bacterium. Infect. Immun. 74:1625–31
     [Google Scholar]
154. Van de Wiele T, Van den Abbeele P, Ossieur W, Possemiers S, Marzorati M 2015. The simulator of the human intestinal microbial ecosystem (SHIME^®). The Impact of Food Bioactives on Health K Verhoeckx, P Cotter, I López-Expósito, C Kleiveland, T Lea et al.305–17 Cham: Springer
     [Google Scholar]
155. van den Brûle S, Ambroise J, Lecloux H, Levard C, Soulas R et al. 2015. Dietary silver nanoparticles can disturb the gut microbiota in mice. Part. Fibre Toxicol. 13:138
     [Google Scholar]
156. Vardakou M, Mercuri A, Barker SA, Craig DQ, Faulks RM, Wickham MS. 2011. Achieving antral grinding forces in biorelevant in vitro models: comparing the USP dissolution apparatus II and the dynamic gastric model with human in vivo data. AAPS PharmSciTech 12:2620–26
     [Google Scholar]
157. Veneranda M, Hu Q, Wang T, Luo Y, Castro K, Madariaga JM. 2018. Formation and characterization of zein-caseinate-pectin complex nanoparticles for encapsulation of eugenol. LWT 89:596–603
     [Google Scholar]
158. Vermeer IT, Henderson LY, Moonen EJ, Engels LG, Dallinga JW et al. 2004. Neutrophil-mediated formation of carcinogenic N-nitroso compounds in an in vitro model for intestinal inflammation. Toxicol. Lett. 154:3175–82
     [Google Scholar]
159. Villenave R, Wales SQ, Hamkins-Indik T, Papafragkou E, Weaver JC et al. 2017. Human gut-on-a-chip supports polarized infection of coxsackie B1 virus in vitro. PLOS ONE 12:2e0169412
     [Google Scholar]
160. Walter E, Janich S, Roessler BJ, Hilfinger JM, Amidon GL. 1996. HT29-MTX/Caco-2 cocultures as an in vitro model for the intestinal epithelium: in vitro-in vivo correlation with permeability data from rats and humans. J. Pharm. Sci. 85:101070–76
     [Google Scholar]
161. Wang A, Yang T, Fan W, Yang Y, Zhu Q et al. 2019. Protein corona liposomes achieve efficient oral insulin delivery by overcoming mucus and epithelial barriers. Adv. Healthc. Mater. 8:121801123
     [Google Scholar]
162. Wang Q, Strab R, Kardos P, Ferguson C, Li J et al. 2008. Application and limitation of inhibitors in drug–transporter interactions studies. Int. J. Pharm. 356:1–212–18
     [Google Scholar]
163. Wang T, Bae M, Lee JY, Luo Y. 2018. Solid lipid-polymer hybrid nanoparticles prepared with natural biomaterials: a new platform for oral delivery of lipophilic bioactives. Food Hydrocoll. 84:581–92
     [Google Scholar]
164. Wang T, Luo Y. 2019. Biological fate of ingested lipid-based nanoparticles: current understanding and future directions. Nanoscale 11:2311048–63
     [Google Scholar]
165. Wang T, Luo Y. 2021. Fabrication strategies and supramolecular interactions of polymer-lipid complex nanoparticles as oral delivery systems. Nano Res. 14:124487–501
     [Google Scholar]
166. Wang T, Xue J, Hu Q, Zhou M, Chang C, Luo Y. 2017a. Synthetic surfactant- and cross-linker-free preparation of highly stable lipid-polymer hybrid nanoparticles as potential oral delivery vehicles. Sci. Rep. 7:12750
     [Google Scholar]
167. Wang T, Xue J, Hu Q, Zhou M, Luo Y. 2017b. Preparation of lipid nanoparticles with high loading capacity and exceptional gastrointestinal stability for potential oral delivery applications. J. Colloid Interface Sci. 507:119–30
     [Google Scholar]
168. Wang W, Xia T, Yu X 2015. Wogonin suppresses inflammatory response and maintains intestinal barrier function via TLR4-MyD88-TAK1-mediated NF-κB pathway in vitro. Inflamm. Res. 64:6423–31
     [Google Scholar]
169. Wickham M, Faulks R, Mann J, Mandalari G. 2012. The design, operation, and application of a dynamic gastric model. Dissolution Technol. 19:315–22
     [Google Scholar]
170. Williams K, Milner J, Boudreau MD, Gokulan K, Cerniglia CE, Khare S. 2015. Effects of subchronic exposure of silver nanoparticles on intestinal microbiota and gut-associated immune responses in the ileum of Sprague-Dawley rats. Nanotoxicology 9:3279–89
     [Google Scholar]
171. Wu Q, Chen T, El-Nezami H, Savidge TC. 2020. Food ingredients in human health: ecological and metabolic perspectives implicating gut microbiota function. Trends Food Sci. Technol. 100:103–17
     [Google Scholar]
172. Wusigale, Liang L, Luo Y. 2020. Casein and pectin: structures, interactions, and applications. Trends Food Sci. Technol. 97:391–403
     [Google Scholar]
173. Xie Y, Hu X, He H, Xia F, Ma Y et al. 2016. Tracking translocation of glucan microparticles targeting M cells: implications for oral drug delivery. J. Mater. Chem. B 4:172864–73
     [Google Scholar]
174. Xue J, Wang T, Hu Q, Zhou M, Luo Y. 2018. Insight into natural biopolymer-emulsified solid lipid nanoparticles for encapsulation of curcumin: effect of loading methods. Food Hydrocoll. 79:110–16
     [Google Scholar]
175. Yamashita S, Yokoyama Y, Hashimoto T, Mizuno M. 2016. A novel in vitro co-culture model comprised of Caco-2/RBL-2H3 cells to evaluate anti-allergic effects of food factors through the intestine. J. Immunol. Methods 435:1–6
     [Google Scholar]
176. Yang H, Yi X, Li L, Ding B. 2017. Estimation of the iron absorption from ferrous glycinate-loaded solid lipid nanoparticles by rat everted intestinal sac model. Food Sci. Technol. Res. 23:4567–73
     [Google Scholar]
177. Yang K, Zhang S, He J, Nie Z. 2021. Polymers and inorganic nanoparticles: a winning combination towards assembled nanostructures for cancer imaging and therapy. Nano Today 36:101046
     [Google Scholar]
178. Yu M, Yang Y, Zhu C, Guo S, Gan Y. 2016. Advances in the transepithelial transport of nanoparticles. Drug Discov. Today 21:71155–61
     [Google Scholar]
179. Zare M, Samani SM, Sobhani Z. 2018. Enhanced intestinal permeation of doxorubicin using chitosan nanoparticles. Adv. Pharm. Bull. 8:3411–17
     [Google Scholar]
180. Zhang Q, Yang H, Sahito B, Li X, Peng L et al. 2020. Nanostructured lipid carriers with exceptional gastrointestinal stability and inhibition of P-gp efflux for improved oral delivery of tilmicosin. Colloids Surfaces B 187:110649
     [Google Scholar]
181. Zhou H, McClements DJ. 2022. Recent advances in the gastrointestinal fate of organic and inorganic nanoparticles in foods. Nanomaterials 12:71099
     [Google Scholar]
182. Zhou M, Hu Q, Wang T, Xue J, Luo Y. 2016a. Effects of different polysaccharides on the formation of egg yolk LDL complex nanogels for nutrient delivery. Carbohydr. Polym. 153:336–44
     [Google Scholar]
183. Zhou M, Hu Q, Wang T, Xue J, Luo Y. 2018. Alginate hydrogel beads as a carrier of low density lipoprotein/pectin nanogels for potential oral delivery applications. Int. J. Biol. Macromol. 120:859–64
     [Google Scholar]
184. Zhou M, Wang T, Hu Q, Luo Y. 2016b. Low density lipoprotein/pectin complex nanogels as potential oral delivery vehicles for curcumin. Food Hydrocoll. 57:20–29
     [Google Scholar]
185. Zhou W, Chow K-H, Fleming E, Oh J 2019. Selective colonization ability of human fecal microbes in different mouse gut environments. ISME J. 13:3805–23
     [Google Scholar]
186. Zur M, Hanson AS, Dahan A. 2014. The complexity of intestinal permeability: assigning the correct BCS classification through careful data interpretation. Eur. J. Pharm. Sci. 61:11–17
     [Google Scholar]