Application of Polymeric Nano-Materials in Management of Inflammatory Bowel Disease

Prasad       Minakshi; Rajesh	      Kumar; Mayukh	      Ghosh; Basanti	      Brar; Manju	      Barnela; Preeti	      Lakhani
doi:10.2174/1568026620666200320113322
Abstract

Inflammatory Bowel Disease (IBD) is an umbrella term used to describe disorders that involve Crohn’s disease (CD), ulcerative colitis (UC) and pouchitis. The disease occurrence is more prevalent in the working group population which not only hampers the well being of an individual but also has negative economical impact on society. The current drug regime used therapy is very costly owing to the chronic nature of the disease leading to several side effects. The condition gets more aggravated due to the lower concentration of drug at the desired site. Therefore, in the present scenario, a therapy is needed which can maximize efficacy, adhere to quality of life, minimize toxicity and doses, be helpful in maintaining and stimulating physical growth of mucosa with minimum disease complications. In this aspect, nanotechnology intervention is one promising field as it can act as a carrier to reduce toxicity, doses and frequency which in turn help in faster recovery. Moreover, nanomedicine and nanodiagnostic techniques will further open a new window for treatment in understanding pathogenesis along with better diagnosis which is poorly understood till now. Therefore the present review is more focused on recent advancements in IBD in the application of nanotechnology.
Keywords: Gastrointestinal, Inflammatory bowel disease, Nanomedicine, RNAi, SCFA, Polymeric nano-materials.
« Previous Next »
Graphical Abstract

[1] 
Crohn, B.B.; Ginzburg, L.; Oppenheimer, G.D. Regional ileitis. A pathological and clinical entity. J. Am. Med. Assoc.,  1932, 99, 1323-1329.
[http://dx.doi.org/10.1001/jama.1932.02740680019005] 
[2] 
Ekbom, A.; Helmick, C.; Zack, M.; Adami, H.O. The epidemiology of inflammatory bowel disease: a large, population-based study in Sweden. Gastroenterology,  1991, 100(2), 350-358.
[http://dx.doi.org/10.1016/0016-5085(91)90202-V] [PMID: 1985033] 
[3] 
Bergman, L.; Krause, U. The incidence of Crohn’s disease in central Sweden. Scand. J. Gastroenterol.,  1975, 10(7), 725-729.
[PMID: 1188306] 
[4] 
Loftus, E.V., Jr; Silverstein, M.D.; Sandborn, W.J.; Tremaine, W.J.; Harmsen, W.S.; Zinsmeister, A.R. Crohn’s disease in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival. Gastroenterology,  1998, 114(6), 1161-1168.
[http://dx.doi.org/10.1016/S0016-5085(98)70421-4] [PMID: 9609752] 
[5] 
The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol. Hepatol.,  2020, 5(1), 17-30.
[http://dx.doi.org/10.1016/S2468-1253(19)30333-4] [PMID: 31648971] 
[6] 
Yang, C.; Merlin, D. Nanoparticle-mediated drug delivery systems for the treatment of ibd: current perspectives. Int. J. Nanomedicine,  2019, 14, 8875-8889.
[http://dx.doi.org/10.2147/IJN.S210315] [PMID: 32009785] 
[7] 
Zhang, M.; Merlin, D. Nanoparticle-based oral drug delivery systems targeting the colon for treatment of ulcerative colitis. Inflamm. Bowel Dis.,  2018, 24(7), 1401-1415.
[http://dx.doi.org/10.1093/ibd/izy123] [PMID: 29788186] 
[8] 
Rosen, M.J.; Dhawan, A.; Saeed, S.A. 1982 Stonnington, C.M.; Philips, S.F.; Melton, L.J.; Zinsmeister, A.R. Chronic ulcerative colitis: incidence and prevalence in a community. Gut,  1987, 28, 402-409.
[9] 
Sedlack, R.E.; Nobrega, F.T.; Kurland, L.T.; Sauer, W.G. Inflammatory colon disease in Rochester, Minnesota, 1935-1964. Gastroenterology,  1972, 62(5), 935-941.
[http://dx.doi.org/10.1016/S0016-5085(72)80110-0] [PMID: 5029078] 
[10] 
Rose, J.D.; Roberts, G.M.; Williams, G.; Mayberry, J.F.; Rhodes, J. Cardiff Crohn’s disease jubilee: the incidence over 50 years. Gut,  1988, 29(3), 346-351.
[http://dx.doi.org/10.1136/gut.29.3.346] [PMID: 3356366] 
[11] 
Girardin, S.E.; Boneca, I.G.; Viala, J.; Chamaillard, M.; Labigne, A.; Thomas, G.; Philpott, D.J.; Sansonetti, P.J. Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J. Biol. Chem.,  2003, 278(11), 8869-8872.
[http://dx.doi.org/10.1074/jbc.C200651200] [PMID: 12527755] 
[12] 
Crohn’s & Colitis Foundation of America. The Facts About Inflammatory Bowel Diseases  Available at:. www.crohnscolitisfoundation.org/sites/default/files/2019-02/Updated-IBD-Factbook.pdf (Accessed 2011).
[13] 
Bernstein, C.N.; Wajda, A.; Svenson, L.W.; MacKenzie, A.; Koehoorn, M.; Jackson, M.; Fedorak, R.; Israel, D.; Blanchard, J.F. The epidemiology of inflammatory bowel disease in Canada: a population-based study. Am. J. Gastroenterol.,  2006, 101(7), 1559-1568.
[http://dx.doi.org/10.1111/j.1572-0241.2006.00603.x] [PMID: 16863561] 
[14] 
Ouyang, Q.; Tandon, R.; Goh, K.L.; Ooi, C.J.; Ogata, H.; Fiocchi, C. The emergence of inflammatory bowel disease in the Asian Pacific region. Curr. Opin. Gastroenterol.,  2005, 21(4), 408-413.
[PMID: 15930979] 
[15] 
Ng, S.C.; Shi, H.Y.; Hamidi, N.; Underwood, F.E.; Tang, W.; Benchimol, E.I.; Panaccione, R.; Ghosh, S.; Wu, J.C.Y.; Chan, F.K.L.; Sung, J.J.Y.; Kaplan, G.G. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet,  2018, 390(10114), 2769-2778.
[http://dx.doi.org/10.1016/S0140-6736(17)32448-0] [PMID: 29050646] 
[16] 
Ng, S.C. Emerging leadership lecture: Inflammatory bowel disease in Asia: emergence of a “Western” disease. J. Gastroenterol. Hepatol.,  2015, 30(3), 440-445.
[http://dx.doi.org/10.1111/jgh.12859] [PMID: 25469874] 
[17] 
May, D.; Pan, S.; Crispin, D.A.; Lai, K.; Bronner, M.P.; Hogan, J.; Hockenbery, D.M.; McIntosh, M.; Brentnall, T.A.; Chen, R. Investigating neoplastic progression of ulcerative colitis with label-free comparative proteomics. J. Proteome Res.,  2011, 10(1), 200-209.
[http://dx.doi.org/10.1021/pr100574p] [PMID: 20828217] 
[18] 
Hanauer, S.B.; Cohen, R.D.; Becker, R.V., III; Larson, L.R.; Vreeland, M.G. Advances in the management of Crohn’s disease: economic and clinical potential of infliximab. Clin. Ther.,  1998, 20(5), 1009-1028.
[http://dx.doi.org/10.1016/S0149-2918(98)80082-9] [PMID: 9829451] 
[19] 
Hay, J.W.; Hay, A.R. Inflammatory bowel disease: costs-of-illness. J. Clin. Gastroenterol.,  1992, 14(4), 309-317.
[http://dx.doi.org/10.1097/00004836-199206000-00009] [PMID: 1607607] 
[20] 
Gibson, T.B.; Ng, E.; Ozminkowski, R.J.; Wang, S.; Burton, W.N.; Goetzel, R.Z.; Maclean, R. The direct and indirect cost burden of Crohn’s disease and ulcerative colitis. J. Occup. Environ. Med.,  2008, 50(11), 1261-1272.
[http://dx.doi.org/10.1097/JOM.0b013e318181b8ca] [PMID: 19001952] 
[21] 
Yu, A.P.; Cabanilla, L.A.; Wu, E.Q.; Mulani, P.M.; Chao, J. The costs of Crohn’s disease in the United States and other Western countries: a systematic review. Curr. Med. Res. Opin.,  2008, 24(2), 319-328.
[http://dx.doi.org/10.1185/030079908X260790] [PMID: 18067689] 
[22] 
Bickston, S.J.; Waters, H.C.; Dabbous, O.; Tang, B.I.; Rahman, M. Administrative claims analysis of all-cause annual costs of care and resource utilization by age category for ulcerative colitis patients. J. Manag. Care Pharm.,  2008, 14(4), 352-362.
[http://dx.doi.org/10.18553/jmcp.2008.14.4.352] [PMID: 18500913] 
[23] 
Cohen, R.D. Inflammatory bowel disease. Clin. Gast. Hept.,  2017, 15, xxi.
[24] 
Cohen, R.D.; Yu, A.P.; Wu, E.Q.; Xie, J.; Mulani, P.M.; Chao, J. Systematic review: the costs of ulcerative colitis in Western countries. Aliment. Pharmacol. Ther.,  2010, 31(7), 693-707.
[http://dx.doi.org/10.1111/j.1365-2036.2010.04234.x] [PMID: 20064142] 
[25] 
Xavier, R.J.; Podolsky, D.K. Unravelling the pathogenesis of inflammatory bowel disease. Nature,  2007, 448(7152), 427-434.
[http://dx.doi.org/10.1038/nature06005] [PMID: 17653185] 
[26] 
Plöger, S.; Stumpff, F.; Penner, G.B.; Schulzke, J-D.; Gäbel, G.; Martens, H.; Shen, Z.; Günzel, D.; Aschenbach, J.R. Microbial butyrate and its role for barrier function in the gastrointestinal tract. Ann. N. Y. Acad. Sci.,  2012, 1258(1), 52-59.
[http://dx.doi.org/10.1111/j.1749-6632.2012.06553.x] [PMID: 22731715] 
[27] 
Goodlad, R.A. Dietary fibre and the risk of colorectal cancer. Gut,  2001, 48(5), 587-589.
[http://dx.doi.org/10.1136/gut.48.5.587] [PMID: 11302948] 
[28] 
Desai, M.S.; Seekatz, A.M.; Koropatkin, N.M.; Kamada, N.; Hickey, C.A.; Wolter, M.; Pudlo, N.A.; Kitamoto, S.; Terrapon, N.; Muller, A.; Young, V.B.; Henrissat, B.; Wilmes, P.; Stappenbeck, T.S.; Núñez, G.; Martens, E.C. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell,  2016, 167(5), 1339-1353.e21.
[http://dx.doi.org/10.1016/j.cell.2016.10.043] [PMID: 27863247] 
[29] 
Frank, D.N.; St Amand, A.L.; Feldman, R.A.; Boedeker, E.C.; Harpaz, N.; Pace, N.R. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc. Natl. Acad. Sci. USA,  2007, 104(34), 13780-13785.
[http://dx.doi.org/10.1073/pnas.0706625104] [PMID: 17699621] 
[30] 
Darfeuille-Michaud, A.; Boudeau, J.; Bulois, P.; Neut, C.; Glasser, A.L.; Barnich, N.; Bringer, M.A.; Swidsinski, A.; Beaugerie, L.; Colombel, J.F. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn’s disease. Gastroenterology,  2004, 127(2), 412-421.
[http://dx.doi.org/10.1053/j.gastro.2004.04.061] [PMID: 15300573] 
[31] 
Darfeuille-Michaud, A.; Neut, C.; Barnich, N.; Lederman, E.; Di Martino, P.; Desreumaux, P.; Gambiez, L.; Joly, B.; Cortot, A.; Colombel, J.F. Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn’s disease. Gastroenterology,  1998, 115(6), 1405-1413.
[http://dx.doi.org/10.1016/S0016-5085(98)70019-8] [PMID: 9834268] 
[32] 
Wachsmann, P.; Lamprecht, A. Polymeric nanoparticles for the selective therapy of inflammatory bowel disease. Methods Enzymol.,  2012, 508, 377-397.
[http://dx.doi.org/10.1016/B978-0-12-391860-4.00019-7] [PMID: 22449936] 
[33] 
Takaishi, H.; Matsuki, T.; Nakazawa, A.; Takada, T.; Kado, S.; Asahara, T.; Kamada, N.; Sakuraba, A.; Yajima, T.; Higuchi, H.; Inoue, N.; Ogata, H.; Iwao, Y.; Nomoto, K.; Tanaka, R.; Hibi, T. Imbalance in intestinal microflora constitution could be involved in the pathogenesis of inflammatory bowel disease. Int. J. Med. Microbiol.,  2008, 298(5-6), 463-472.
[http://dx.doi.org/10.1016/j.ijmm.2007.07.016] [PMID: 17897884] 
[34] 
Bibiloni, R.; Mangold, M.; Madsen, K.L.; Fedorak, R.N.; Tannock, G.W. The bacteriology of biopsies differs between newly diagnosed, untreated, Crohn’s disease and ulcerative colitis patients. J. Med. Microbiol.,  2006, 55(Pt 8), 1141-1149.
[http://dx.doi.org/10.1099/jmm.0.46498-0] [PMID: 16849736] 
[35] 
Barnich, N.; Boudeau, J.; Claret, L.; Darfeuille-Michaud, A. Regulatory and functional co-operation of flagella and type 1 pili in adhesive and invasive abilities of AIEC strain LF82 isolated from a patient with Crohn’s disease. Mol. Microbiol.,  2003, 48(3), 781-794.
[http://dx.doi.org/10.1046/j.1365-2958.2003.03468.x] [PMID: 12694621] 
[36] 
Boudeau, J.; Barnich, N.; Darfeuille-Michaud, A. Type 1 pili-mediated adherence of Escherichia coli strain LF82 isolated from Crohn’s disease is involved in bacterial invasion of intestinal epithelial cells. Mol. Microbiol.,  2001, 39(5), 1272-1284.
[http://dx.doi.org/10.1111/j.1365-2958.2001.02315.x] [PMID: 11251843] 
[37] 
Glasser, A.L.; Boudeau, J.; Barnich, N.; Perruchot, M.H.; Colombel, J.F.; Darfeuille-Michaud, A. Adherent invasive Escherichia coli strains from patients with Crohn’s disease survive and replicate within macrophages without inducing host cell death. Infect. Immun.,  2001, 69(9), 5529-5537.
[http://dx.doi.org/10.1128/IAI.69.9.5529-5537.2001] [PMID: 11500426] 
[38] 
Bedford, A.; Gong, J. Implications of butyrate and its derivatives for gut health and animal production. Anim Nutr,  2018, 4(2), 151-159.
[http://dx.doi.org/10.1016/j.aninu.2017.08.010] [PMID: 30140754] 
[39] 
Corrêa-Oliveira, R.; Fachi, J.L.; Vieira, A.; Sato, F.T.; Vinolo, M.A.R. Regulation of immune cell function by short-chain fatty acids. Clin. Transl. Immunology,  2016, 5(4) e73
[http://dx.doi.org/10.1038/cti.2016.17] [PMID: 27195116] 
[40] 
Millard, A.L.; Mertes, P.M.; Ittelet, D.; Villard, F.; Jeannesson, P.; Bernard, J. Butyrate affects differentiation, maturation and function of human monocyte-derived dendritic cells and macrophages. Clin. Exp. Immunol.,  2002, 130(2), 245-255.
[http://dx.doi.org/10.1046/j.0009-9104.2002.01977.x] [PMID: 12390312] 
[41] 
Kim, C.H.; Park, J.; Kim, M. Gut microbiota-derived short-chain Fatty acids, T cells, and inflammation. Immune Netw.,  2014, 14(6), 277-288.
[http://dx.doi.org/10.4110/in.2014.14.6.277] [PMID: 25550694] 
[42] 
Nastasi, C.; Fredholm, S.; Willerslev-Olsen, A.; Hansen, M.; Bonefeld, C.M.; Geisler, C.; Andersen, M.H.; Ødum, N.; Woetmann, A. Butyrate and propionate inhibit antigen-specific CD8+ T cell activation by suppressing IL-12 production by antigen-presenting cells. Sci. Rep.,  2017, 7(1), 14516.
[http://dx.doi.org/10.1038/s41598-017-15099-w] [PMID: 29109552] 
[43] 
Iyer, S.S.; Gensollen, T.; Gandhi, A.; Oh, S.F.; Neves, J.F.; Collin, F.; Lavin, R.; Serra, C.; Glickman, J.; de Silva, P.S.A.; Sartor, R.B.; Besra, G.; Hauser, R.; Maxwell, A.; Llebaria, A.; Blumberg, R.S. Dietary and microbial oxazoles induce intestinal inflammation by modulating aryl hydrocarbon receptor responses. Cell,  2018, 173(5), 1123-1134.e11.
[http://dx.doi.org/10.1016/j.cell.2018.04.037] [PMID: 29775592] 
[44] 
Ahmed, I.; Roy, B.C.; Khan, S.A.; Septer, S.; Umar, S. Microbiome, metabolome and inflammatory bowel disease. Microorganisms,  2016, 4(2), 20.
[http://dx.doi.org/10.3390/microorganisms4020020] [PMID: 27681914] 
[45] 
Guan, G.; Lan, S. Implications of antioxidant systems in inflammatory bowel disease. BioMed Res. Int.,  2018, 2018 1290179
[http://dx.doi.org/10.1155/2018/1290179] [PMID: 29854724] 
[46] 
Gearry, R.B.; Richardson, A.; Frampton, C.M.; Collett, J.A.; Burt, M.J.; Chapman, B.A.; Barclay, M.L. High incidence of Crohn’s disease in Canterbury, New Zealand: results of an epidemiologic study. Inflamm. Bowel Dis.,  2006, 12(10), 936-943.
[http://dx.doi.org/10.1097/01.mib.0000231572.88806.b9] [PMID: 17012964] 
[47] 
Lih-Brody, L.; Powell, S.R.; Collier, K.P.; Reddy, G.M.; Cerchia, R.; Kahn, E.; Weissman, G.S.; Katz, S.; Floyd, R.A.; McKinley, M.J.; Fisher, S.E.; Mullin, G.E. Increased oxidative stress and decreased antioxidant defenses in mucosa of inflammatory bowel disease. Dig. Dis. Sci.,  1996, 41(10), 2078-2086.
[http://dx.doi.org/10.1007/BF02093613] [PMID: 8888724] 
[48] 
Simmonds, N.J.; Allen, R.E.; Stevens, T.R.; Van Someren, R.N.; Blake, D.R.; Rampton, D.S. Chemiluminescence assay of mucosal reactive oxygen metabolites in inflammatory bowel disease. Gastroenterology,  1992, 103(1), 186-196.
[http://dx.doi.org/10.1016/0016-5085(92)91112-H] [PMID: 1319369] 
[49] 
Mahida, Y.R.; Wu, K.C.; Jewell, D.P. Respiratory burst activity of intestinal macrophages in normal and inflammatory bowel disease. Gut,  1989, 30(10), 1362-1370.
[http://dx.doi.org/10.1136/gut.30.10.1362] [PMID: 2511088] 
[50] 
Friedrich, M.; Pohin, M.; Powrie, F. Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. Immunity,  2019, 50(4), 992-1006.
[http://dx.doi.org/10.1016/j.immuni.2019.03.017] [PMID: 30995511] 
[51] 
Magnusson, M.K.; Brynjólfsson, S.F.; Dige, A.; Uronen-Hansson, H.; Börjesson, L.G.; Bengtsson, J.L.; Gudjonsson, S.; Öhman, L.; Agnholt, J.; Sjövall, H.; Agace, W.W.; Wick, M.J. Macrophage and dendritic cell subsets in IBD: ALDH+ cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation. Mucosal Immunol.,  2016, 9(1), 171-182.
[http://dx.doi.org/10.1038/mi.2015.48] [PMID: 26080709] 
[52] 
Joeris, T.; Müller-Luda, K.; Agace, W.W.; Mowat, A.M. Diversity and functions of intestinal mononuclear phagocytes. Mucosal Immunol.,  2017, 10(4), 845-864.
[http://dx.doi.org/10.1038/mi.2017.22] [PMID: 28378807] 
[53] 
Ahluwalia, B.; Moraes, L.; Magnusson, M.K.; Öhman, L. Immunopathogenesis of inflammatory bowel disease and mechanisms of biological therapies. Scand. J. Gastroenterol.,  2018, 53(4), 379-389.
[http://dx.doi.org/10.1080/00365521.2018.1447597] [PMID: 29523023] 
[54] 
Strober, W.; Watanabe, T. NOD2, an intracellular innate immune sensor involved in host defense and Crohn’s disease. Mucosal Immunol.,  2011, 4(5), 484-495.
[http://dx.doi.org/10.1038/mi.2011.29] [PMID: 21750585] 
[55] 
Bonen, D.K.; Ogura, Y.; Nicolae, D.L.; Inohara, N.; Saab, L.; Tanabe, T.; Chen, F.F.; Foster, S.J.; Duerr, R.H.; Brant, S.R.; Cho, J.H.; Nuñez, G. Crohn’s disease-associated NOD2 variants share a signaling defect in response to lipopolysaccharide and peptidoglycan. Gastroenterology,  2003, 124(1), 140-146.
[http://dx.doi.org/10.1053/gast.2003.50019] [PMID: 12512038] 
[56] 
Wehkamp, J.; Fellermann, K.; Herrlinger, K.R.; Bevins, C.L.; Stange, E.F. Mechanisms of disease: defensins in gastrointestinal diseases. Nat. Clin. Pract. Gastroenterol. Hepatol.,  2005, 2(9), 406-415.
[http://dx.doi.org/10.1038/ncpgasthep0265] [PMID: 16265431] 
[57] 
Wehkamp, J.; Salzman, N.H.; Porter, E.; Nuding, S.; Weichenthal, M.; Petras, R.E.; Shen, B.; Schaeffeler, E.; Schwab, M.; Linzmeier, R.; Feathers, R.W.; Chu, H.; Lima, H., Jr; Fellermann, K.; Ganz, T.; Stange, E.F.; Bevins, C.L. Reduced Paneth cell alpha-defensins in ileal Crohn’s disease. Proc. Natl. Acad. Sci. USA,  2005, 102(50), 18129-18134.
[http://dx.doi.org/10.1073/pnas.0505256102] [PMID: 16330776] 
[58] 
Hua, S.; Marks, E.; Schneider, J.J.; Keely, S. Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue. Nanomedicine (Lond.),  2015, 11(5), 1117-1132.
[http://dx.doi.org/10.1016/j.nano.2015.02.018] [PMID: 25784453] 
[59] 
Zhang, S.; Langer, R.; Traverso, G. Nanoparticulate drug delivery systems targeting inflammation for treatment of inflammatory bowel disease. Nano Today,  2017, 16, 82-96.
[http://dx.doi.org/10.1016/j.nantod.2017.08.006] [PMID: 31186671] 
[60] 
Ensign, L.M.; Cone, R.; Hanes, J. Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers. Adv. Drug Deliv. Rev.,  2012, 64(6), 557-570.
[http://dx.doi.org/10.1016/j.addr.2011.12.009] [PMID: 22212900] 
[61] 
Wang, Y.Y.; Lai, S.K.; So, C.; Schneider, C.; Cone, R.; Hanes, J. Mucoadhesive nanoparticles may disrupt the protective human mucus barrier by altering its microstructure. PLoS One,  2011, 6(6) e21547
[http://dx.doi.org/10.1371/journal.pone.0021547] [PMID: 21738703] 
[62] 
Johnson, L.; Christensen, J.; Jackson, M. Physiology of the gastrointestinal tract; Raven Press: New York, 1987. 
[63] 
Mura, C.; Nácher, A.; Merino, V.; Merino-Sanjuan, M.; Carda, C.; Ruiz, A.; Manconi, M.; Loy, G.; Fadda, A.M.; Diez-Sales, O. N-Succinyl-chitosan systems for 5-aminosalicylic acid colon delivery: in vivo study with TNBS-induced colitis model in rats. Int. J. Pharm.,  2011, 416(1), 145-154.
[http://dx.doi.org/10.1016/j.ijpharm.2011.06.025] [PMID: 21723929] 
[64] 
Maisel, K.; Ensign, L.; Reddy, M.; Cone, R.; Hanes, J. Effect of surface chemistry on nanoparticle interaction with gastrointestinal mucus and distribution in the gastrointestinal tract following oral and rectal administration in the mouse. J. Control. Release,  2015, 197, 48-57.
[http://dx.doi.org/10.1016/j.jconrel.2014.10.026] [PMID: 25449804] 
[65] 
Ijssennagger, N.; van der Meer, R.; van Mil, S.W.C. Sulfide as a mucus barrier-breaker in inflammatory bowel disease? Trends Mol. Med.,  2016, 22(3), 190-199.
[http://dx.doi.org/10.1016/j.molmed.2016.01.002] [PMID: 26852376] 
[66] 
Lamprecht, A.; Schäfer, U.; Lehr, C-M. Size-dependent bioadhesion of micro- and nanoparticulate carriers to the inflamed colonic mucosa. Pharm. Res.,  2001, 18(6), 788-793.
[http://dx.doi.org/10.1023/A:1011032328064] [PMID: 11474782] 
[67] 
Rejman, J.; Oberle, V.; Zuhorn, I.S.; Hoekstra, D. Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis. Biochem. J.,  2004, 377(Pt 1), 159-169.
[http://dx.doi.org/10.1042/bj20031253] [PMID: 14505488] 
[68] 
Wang, Z.; Tiruppathi, C.; Minshall, R.D.; Malik, A.B. Size and dynamics of caveolae studied using nanoparticles in living endothelial cells. ACS Nano,  2009, 3(12), 4110-4116.
[http://dx.doi.org/10.1021/nn9012274] [PMID: 19919048] 
[69] 
Pridgen, E.M.; Alexis, F.; Farokhzad, O.C. Polymeric nanoparticle drug delivery technologies for oral delivery applications. Expert Opin. Drug Deliv.,  2015, 12(9), 1459-1473.
[http://dx.doi.org/10.1517/17425247.2015.1018175] [PMID: 25813361] 
[70] 
Jose, S.; Dhanya, K.; Cinu, T.A.; Litty, J.; Chacko, A.J. Colon Targeted Drug Delivery: Different Approaches. J. Young Pharm.,  2009, 1, 13-19.
[http://dx.doi.org/10.4103/0975-1483.51869] 
[71] 
Ingersoll, S.A.; Ayyadurai, S.; Charania, M.A.; Laroui, H.; Yan, Y.; Merlin, D. The role and pathophysiological relevance of membrane transporter PepT1 in intestinal inflammation and inflammatory bowel disease. Am. J. Physiol. Gastrointest. Liver Physiol.,  2012, 302(5), G484-G492.
[http://dx.doi.org/10.1152/ajpgi.00477.2011] [PMID: 22194420] 
[72] 
Martirosyan, A.; Polet, M.; Bazes, A.; Sergent, T.; Schneider, Y-J. Food nanoparticles and intestinal inflammation: A real risk? Inflamm. Bowel Dis., 2012.
[http://dx.doi.org/10.5772/52887] 
[73] 
Lamprecht, A. IBD: selective nanoparticle adhesion can enhance colitis therapy. Nat. Rev. Gastroenterol. Hepatol.,  2010, 7(6), 311-312.
[http://dx.doi.org/10.1038/nrgastro.2010.66] [PMID: 20523352] 
[74] 
DeMario, M.D.; Ratain, M.J. Oral chemotherapy: rationale and future directions. J. Clin. Oncol.,  1998, 16(7), 2557-2567.
[http://dx.doi.org/10.1200/JCO.1998.16.7.2557] [PMID: 9667278] 
[75] 
Salama, N.N.; Eddington, N.D.; Fasano, A. Tight junction modulation and its relationship to drug delivery. Adv. Drug Deliv. Rev.,  2006, 58(1), 15-28.
[http://dx.doi.org/10.1016/j.addr.2006.01.003] [PMID: 16517003] 
[76] 
Mitic, L.L.; Van Itallie, C.M.; Anderson, J.M. Molecular physiology and pathophysiology of tight junctions I. Tight junction structure and function: lessons from mutant animals and proteins. Am. J. Physiol. Gastrointest. Liver Physiol.,  2000, 279(2), G250-G254.
[http://dx.doi.org/10.1152/ajpgi.2000.279.2.G250] [PMID: 10915631] 
[77] 
Stamatovic, S.M.; Keep, R.F.; Kunkel, S.L.; Andjelkovic, A.V. Potential role of MCP-1 in endothelial cell tight junction ‘opening’: signaling via Rho and Rho kinase. J. Cell Sci.,  2003, 116(Pt 22), 4615-4628.
[http://dx.doi.org/10.1242/jcs.00755] [PMID: 14576355] 
[78] 
Tsukita, S.; Furuse, M.; Itoh, M. Multifunctional strands in tight junctions. Nat. Rev. Mol. Cell Biol.,  2001, 2(4), 285-293.
[http://dx.doi.org/10.1038/35067088] [PMID: 11283726] 
[79] 
Clark, M.A.; Jepson, M.A.; Hirst, B.H. Exploiting M cells for drug and vaccine delivery. Adv. Drug Deliv. Rev.,  2001, 50(1-2), 81-106.
[http://dx.doi.org/10.1016/S0169-409X(01)00149-1] [PMID: 11489335] 
[80] 
Porta, C.; James, P.S.; Phillips, A.D.; Savidge, T.C.; Smith, M.W.; Cremaschi, D. Confocal analysis of fluorescent bead uptake by mouse Peyer’s patch follicle-associated M cells. Exp. Physiol.,  1992, 77(6), 929-932.
[http://dx.doi.org/10.1113/expphysiol.1992.sp003662] [PMID: 1489550] 
[81] 
Brayden, D.J. Oral vaccination in man using antigens in particles: current status. Eur. J. Pharm. Sci.,  2001, 14(3), 183-189.
[http://dx.doi.org/10.1016/S0928-0987(01)00175-0] [PMID: 11576821] 
[82] 
Eldridge, J.H.; Hammond, C.J.; Meulbroek, J.A.; Jay, K.; Richard, M.; Tice, T.R. Controlled vaccine release in the gut-associated lymphoid tissues. I. Orally administered biodegradable microspheres target the Peyer’s patches. J. Control. Release,  1990, 11, 205-214.
[http://dx.doi.org/10.1016/0168-3659(90)90133-E] 
[83] 
Sass, W.; Dreyer, H.P.; Seifert, J. Rapid insorption of small particles in the gut. Am. J. Gastroenterol.,  1990, 85(3), 255-260.
[PMID: 2309677] 
[84] 
Weissenboeck, A.; Bogner, E.; Wirth, M.; Gabor, F. Binding and uptake of wheat germ agglutinin-grafted PLGA-nanospheres by caco-2 monolayers. Pharm. Res.,  2004, 21(10), 1917-1923.
[http://dx.doi.org/10.1023/B:PHAM.0000045247.09724.26] [PMID: 15553240] 
[85] 
Lochner, N.; Pittner, F.; Wirth, M.; Gabor, F. Wheat germ agglutinin binds to the epidermal growth factor receptor of artificial Caco-2 membranes as detected by silver nanoparticle enhanced fluorescence. Pharm. Res.,  2003, 20(5), 833-839.
[http://dx.doi.org/10.1023/A:1023406224028] [PMID: 12751642] 
[86] 
Roger, E.; Kalscheuer, S.; Kirtane, A.; Guru, B.R.; Grill, A.E.; Whittum-Hudson, J.; Panyam, J. Folic acid functionalized nanoparticles for enhanced oral drug delivery. Mol. Pharm.,  2012, 9(7), 2103-2110.
[http://dx.doi.org/10.1021/mp2005388] [PMID: 22670575] 
[87] 
Kountouras, J.; Chatzopoulos, D.; Zavos, C. Reactive oxygen metabolites and upper gastrointestinal diseases. Hepatogastroenterology,  2001, 48(39), 743-751.
[PMID: 11462918] 
[88] 
Wilson, D.S.; Dalmasso, G.; Wang, L.; Sitaraman, S.V.; Merlin, D.; Murthy, N. Orally delivered thioketal nanoparticles loaded with TNF-α-siRNA target inflammation and inhibit gene expression in the intestines. Nat. Mater.,  2010, 9(11), 923-928.
[http://dx.doi.org/10.1038/nmat2859] [PMID: 20935658] 
[89] 
Kakuta, H. Necessity is the mother of invention: an ingenious method for leukocyte-targeted delivery of siRNA in stabilized nanoparticles demonstrates a role of cyclin D1 in inflammation. ChemMedChem,  2008, 3(7), 1024-1025.
[http://dx.doi.org/10.1002/cmdc.200800095] [PMID: 18465763] 
[90] 
Peppercorn, M.A.; Goldman, P. The role of intestinal bacteria in the metabolism of salicylazosulfapyridine. J. Pharmacol. Exp. Ther.,  1972, 181(3), 555-562.
[PMID: 4402374] 
[91] 
Guo, J.; Jiang, X.; Gui, S. RNA interference-based nanosystems for inflammatory bowel disease therapy. Int. J. Nanomedicine,  2016, 11, 5287-5310.
[http://dx.doi.org/10.2147/IJN.S116902] [PMID: 27789943] 
[92] 
Pentasa (mesalamine) Controlled-Release Capsules (prescribing information). Available at:. www.accessdata.fda.gov/ drugsatfda_docs/nda/2015/020049Orig1s027.pdf
[93] 
Asacol (mesalamine) Delayed-Release Tablets (prescribing information). Available at:. https://www.rxlist.com/asacol-drug.htm
[94] 
Lialda (mesalamine) delayed release tablets (prescribing information). Available at:. https://www.accessdata.fda.gov/ drugsatfda_docs/label/2009/022000s002lbl.pdf
[95] 
Nielsen, O.H. Sulfasalazine intolerance. A retrospective survey of the reasons for discontinuing treatment with sulfasalazine in patients with chronic inflammatory bowel disease. Scand. J. Gastroenterol.,  1982, 17(3), 389-393.
[http://dx.doi.org/10.3109/00365528209182073] [PMID: 6127793] 
[96] 
Nielsen, O.H.; Munck, L.K. Drug insight: aminosalicylates for the treatment of IBD. Nat. Clin. Pract. Gastroenterol. Hepatol.,  2007, 4(3), 160-170.
[http://dx.doi.org/10.1038/ncpgasthep0696] [PMID: 17339853] 
[97] 
Lichtenstein, G.R.; Abreu, M.T.; Cohen, R.; Tremaine, W. American Gastroenterological Association Institute medical position statement on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology,  2006, 130(3), 935-939.
[http://dx.doi.org/10.1053/j.gastro.2006.01.047] [PMID: 16530531] 
[98] 
Stein, R.B.; Hanauer, S.B. Comparative tolerability of treatments for inflammatory bowel disease. Drug Saf.,  2000, 23(5), 429-448.
[http://dx.doi.org/10.2165/00002018-200023050-00006] [PMID: 11085348] 
[99] 
Yang, Y.X.; Lichtenstein, G.R. Corticosteroids in Crohn’s disease. Am. J. Gastroenterol.,  2002, 97(4), 803-823.
[http://dx.doi.org/10.1111/j.1572-0241.2002.05596.x] [PMID: 12003413] 
[100] 
Tiede, I.; Fritz, G.; Strand, S.; Poppe, D.; Dvorsky, R.; Strand, D.; Lehr, H.A.; Wirtz, S.; Becker, C.; Atreya, R.; Mudter, J.; Hildner, K.; Bartsch, B.; Holtmann, M.; Blumberg, R.; Walczak, H.; Iven, H.; Galle, P.R.; Ahmadian, M.R.; Neurath, M.F. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J. Clin. Invest.,  2003, 111(8), 1133-1145.
[http://dx.doi.org/10.1172/JCI16432] [PMID: 12697733] 
[101] 
Candy, S.; Wright, J.; Gerber, M.; Adams, G.; Gerig, M.; Goodman, R. A controlled double blind study of azathioprine in the management of Crohn’s disease. Gut,  1995, 37(5), 674-678.
[http://dx.doi.org/10.1136/gut.37.5.674] [PMID: 8549944] 
[102] 
Ardizzone, S.; Maconi, G.; Sampietro, G.M.; Russo, A.; Radice, E.; Colombo, E.; Imbesi, V.; Molteni, M.; Danelli, P.G.; Taschieri, A.M.; Bianchi Porro, G. Azathioprine and mesalamine for prevention of relapse after conservative surgery for Crohn’s disease. Gastroenterology,  2004, 127(3), 730-740.
[http://dx.doi.org/10.1053/j.gastro.2004.06.051] [PMID: 15362028] 
[103] 
Goldenberg, B.A.; Rawsthorne, P.; Bernstein, C.N. The utility of 6-thioguanine metabolite levels in managing patients with inflammatory bowel disease. Am. J. Gastroenterol.,  2004, 99(9), 1744-1748.
[http://dx.doi.org/10.1111/j.1572-0241.2004.30415.x] [PMID: 15330913] 
[104] 
Gupta, P.; Gokhale, R.; Kirschner, B.S. 6-mercaptopurine metabolite levels in children with inflammatory bowel disease. J. Pediatr. Gastroenterol. Nutr.,  2001, 33(4), 450-454.
[http://dx.doi.org/10.1097/00005176-200110000-00006] [PMID: 11698762] 
[105] 
Lowry, P.W.; Franklin, C.L.; Weaver, A.L.; Pike, M.G.; Mays, D.C.; Tremaine, W.J.; Lipsky, J.J.; Sandborn, W.J. Measurement of thiopurine methyltransferase activity and azathioprine metabolites in patients with inflammatory bowel disease. Gut,  2001, 49(5), 665-670.
[http://dx.doi.org/10.1136/gut.49.5.665] [PMID: 11600469] 
[106] 
Lees, C.W.; Maan, A.K.; Hansoti, B.; Satsangi, J.; Arnott, I.D. Tolerability and safety of mercaptopurine in azathioprine-intolerant patients with inflammatory bowel disease. Aliment. Pharmacol. Ther.,  2008, 27(3), 220-227.
[http://dx.doi.org/10.1111/j.1365-2036.2007.03570.x] [PMID: 17988235] 
[107] 
Cronstein, B.N.; Naime, D.; Ostad, E. The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J. Clin. Invest.,  1993, 92(6), 2675-2682.
[http://dx.doi.org/10.1172/JCI116884] [PMID: 8254024] 
[108] 
Rampton, D.S. Methotrexate in Crohn’s disease. Gut,  2001, 48(6), 790-791.
[http://dx.doi.org/10.1136/gut.48.6.790] [PMID: 11358896] 
[109] 
Ortiz, Z.; Shea, B.; Suarez-Almazor, M.E.; Moher, D.; Wells, G.A.; Tugwell, P. The efficacy of folic acid and folinic acid in reducing methotrexate gastrointestinal toxicity in rheumatoid arthritis. A metaanalysis of randomized controlled trials. J. Rheumatol.,  1998, 25(1), 36-43.
[PMID: 9458200] 
[110] 
Jordan, R.L.; Wilson, J.G.; Schumacher, H.J. Embryotoxicity of the folate antagonist methotrexate in rats and rabbits. Teratology,  1977, 15(1), 73-79.
[http://dx.doi.org/10.1002/tera.1420150110] [PMID: 841483] 
[111] 
Pham, C.Q.; Efros, C.B.; Berardi, R.R. Cyclosporine for severe ulcerative colitis. Ann. Pharmacother.,  2006, 40(1), 96-101.
[http://dx.doi.org/10.1345/aph.1G374] [PMID: 16368919] 
[112] 
Kornbluth, A.; Lichtiger, S.; Present, D.H. Long term results of oral cyclosporine in patients with severe ulcerative colitis: A double-blind, randomized, multicenter trial. Gastroenterology,  1994, 106, A714. [abstract].
[113] 
D’Haens, G.; Lemmens, L.; Geboes, K.; Vandeputte, L.; Van Acker, F.; Mortelmans, L.; Peeters, M.; Vermeire, S.; Penninckx, F.; Nevens, F.; Hiele, M.; Rutgeerts, P. Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis. Gastroenterology,  2001, 120(6), 1323-1329.
[http://dx.doi.org/10.1053/gast.2001.23983] [PMID: 11313301] 
[114] 
Sternthal, M.B.; Murphy, S.J.; George, J.; Kornbluth, A.; Lichtiger, S.; Present, D.H. Adverse events associated with the use of cyclosporine in patients with inflammatory bowel disease. Am. J. Gastroenterol.,  2008, 103(4), 937-943.
[http://dx.doi.org/10.1111/j.1572-0241.2007.01718.x] [PMID: 18177449] 
[115] 
Rutgeerts, P.; Vermeire, S.; Van Assche, G. Biological therapies for inflammatory bowel diseases. Gastroenterology,  2009, 136(4), 1182-1197.
[http://dx.doi.org/10.1053/j.gastro.2009.02.001] [PMID: 19249397] 
[116] 
Tracey, D.; Klareskog, L.; Sasso, E.H.; Salfeld, J.G.; Tak, P.P. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol. Ther.,  2008, 117(2), 244-279.
[http://dx.doi.org/10.1016/j.pharmthera.2007.10.001] [PMID: 18155297] 
[117] 
Colombel, J.F.; Sandborn, W.J.; Reinisch, W.; Mantzaris, G.J.; Kornbluth, A.; Rachmilewitz, D.; Lichtiger, S.; D’Haens, G.; Diamond, R.H.; Broussard, D.L.; Tang, K.L.; van der Woude, C.J.; Rutgeerts, P. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N. Engl. J. Med.,  2010, 362(15), 1383-1395.
[http://dx.doi.org/10.1056/NEJMoa0904492] [PMID: 20393175] 
[118] 
Nielsen, O.H. New strategies for treatment of inflammatory bowel disease. Front. Med. (Lausanne),  2014, 1(3), 3.
[http://dx.doi.org/10.3389/fmed.2014.00003] [PMID: 25685754] 
[119] 
Carbone, J.; Perez-Rojas, J.; Sarmiento, E. Infectious pulmonary complications in patients treated with anti-TNF-alpha monoclonal antibodies and soluble TNF receptor. Curr. Infect. Dis. Rep.,  2009, 11(3), 229-236.
[http://dx.doi.org/10.1007/s11908-009-0034-2] [PMID: 19366566] 
[120] 
Peyrin-Biroulet, L.; Deltenre, P.; de Suray, N.; Branche, J.; Sandborn, W.J.; Colombel, J.F. Efficacy and safety of tumor necrosis factor antagonists in Crohn’s disease: meta-analysis of placebo-controlled trials. Clin. Gastroenterol. Hepatol.,  2008, 6(6), 644-653.
[http://dx.doi.org/10.1016/j.cgh.2008.03.014] [PMID: 18550004] 
[121] 
Reddy, J.G.; Loftus, E.V., Jr Safety of infliximab and other biologic agents in the inflammatory bowel diseases. Gastroenterol. Clin. North Am.,  2006, 35(4), 837-855.
[http://dx.doi.org/10.1016/j.gtc.2006.09.008] [PMID: 17129816] 
[122] 
Vermeire, S.; Van Assche, G.; Rutgeerts, P. Serum sickness, encephalitis and other complications of anti-cytokine therapy. Best Pract. Res. Clin. Gastroenterol.,  2009, 23(1), 101-112.
[http://dx.doi.org/10.1016/j.bpg.2008.12.005] [PMID: 19258190] 
[123] 
Tripathi, K.; Feuerstein, J.D. New developments in ulcerative colitis: latest evidence on management, treatment, and maintenance. Drugs Context,  2019, 8 212572
[http://dx.doi.org/10.7573/dic.212572] [PMID: 31065290] 
[124] 
Lichtenstein, G.R.; Feagan, B.G.; Cohen, R.D.; Salzberg, B.A.; Diamond, R.H.; Chen, D.M.; Pritchard, M.L.; Sandborn, W.J. Serious infections and mortality in association with therapies for Crohn’s disease: TREAT registry. Clin. Gastroenterol. Hepatol.,  2006, 4(5), 621-630.
[http://dx.doi.org/10.1016/j.cgh.2006.03.002] [PMID: 16678077] 
[125] 
Cohen, R.D. Inflammatory bowel disease: Diagnosis and therapeutic; Springer: Berlin, 2017. 
[126] 
Nie, Y.; Lin, Q.; Luo, F. Effects of non-starch polysaccharides on inflammatory bowel disease. Int. J. Mol. Sci.,  2017, 18(7), 1372.
[http://dx.doi.org/10.3390/ijms18071372] [PMID: 28654020] 
[127] 
American Gastroenterological Association. New drugs for inflammatory bowel disease (IBD). Available from:. https://www.eurekalert.org/pub_releases/2018-01/agandf011618. php  (Accessed 2018).
[128] 
Xiao, B.; Merlin, D. Oral colon-specific therapeutic approaches toward treatment of inflammatory bowel disease. Expert Opin. Drug Deliv.,  2012, 9(11), 1393-1407.
[http://dx.doi.org/10.1517/17425247.2012.730517] [PMID: 23036075] 
[129] 
Collnot, E.M.; Ali, H.; Lehr, C.M. Nano- and microparticulate drug carriers for targeting of the inflamed intestinal mucosa. J. Control. Release,  2012, 161(2), 235-246.
[http://dx.doi.org/10.1016/j.jconrel.2012.01.028] [PMID: 22306429] 
[130] 
Lamprecht, A.; Ubrich, N.; Yamamoto, H.; Schäfer, U.; Takeuchi, H.; Maincent, P.; Kawashima, Y.; Lehr, C.M. Biodegradable nanoparticles for targeted drug delivery in treatment of inflammatory bowel disease. J. Pharmacol. Exp. Ther.,  2001, 299(2), 775-781.
[PMID: 11602694] 
[131] 
Hardy, J.G.; Wilson, C.G.; Wood, E. Drug delivery to the proximal colon. J. Pharm. Pharmacol.,  1985, 37(12), 874-877.
[http://dx.doi.org/10.1111/j.2042-7158.1985.tb04992.x] [PMID: 2868094] 
[132] 
Adkin, D.A.; Davis, S.S.; Sparrow, R.A.; Wilding, I.R. Colonic transit of different sized tablets in healthy subjects. J. Control. Release,  1993, 23, 147-156.
[http://dx.doi.org/10.1016/0168-3659(93)90040-C] 
[133] 
Date, A.A.; Hanes, J.; Ensign, L.M. Nanoparticles for oral delivery: Design, evaluation and state-of-the-art. J. Control. Release,  2016, 240, 504-526.
[http://dx.doi.org/10.1016/j.jconrel.2016.06.016] [PMID: 27292178] 
[134] 
Tamura, A.; Ozawa, K.; Ohya, T.; Tsuyama, N.; Eyring, E.M.; Masujima, T. Nanokinetics of drug molecule transport into a single cell. Nanomedicine (Lond.),  2006, 1(3), 345-350.
[http://dx.doi.org/10.2217/17435889.1.3.345] [PMID: 17716164] 
[135] 
Powell, J.J.; Faria, N.; Thomas-McKay, E.; Pele, L.C. Origin and fate of dietary nanoparticles and microparticles in the gastrointestinal tract. J. Autoimmun.,  2010, 34(3), J226-J233.
[http://dx.doi.org/10.1016/j.jaut.2009.11.006] [PMID: 20096538] 
[136] 
Yun, Y.; Cho, Y.W.; Park, K. Nanoparticles for oral delivery: targeted nanoparticles with peptidic ligands for oral protein delivery. Adv. Drug Deliv. Rev.,  2013, 65(6), 822-832.
[http://dx.doi.org/10.1016/j.addr.2012.10.007] [PMID: 23123292] 
[137] 
Han, H.K.; Shin, H.J.; Ha, D.H. Improved oral bioavailability of alendronate via the mucoadhesive liposomal delivery system. Eur. J. Pharm. Sci.,  2012, 46(5), 500-507.
[http://dx.doi.org/10.1016/j.ejps.2012.04.002] [PMID: 22522117] 
[138] 
Liu, L.; Fishman, M.L.; Hicks, K.B.; Kende, M. Interaction of various pectin formulations with porcine colonic tissues. Biomaterials,  2005, 26(29), 5907-5916.
[http://dx.doi.org/10.1016/j.biomaterials.2005.03.005] [PMID: 15949556] 
[139] 
Tirosh, B.; Khatib, N.; Barenholz, Y.; Nissan, A.; Rubinstein, A. Transferrin as a luminal target for negatively charged liposomes in the inflamed colonic mucosa. Mol. Pharm.,  2009, 6(4), 1083-1091.
[http://dx.doi.org/10.1021/mp9000926] [PMID: 19603812] 
[140] 
Carlson, M.; Raab, Y.; Peterson, C.; Hällgren, R.; Venge, P. Increased intraluminal release of eosinophil granule proteins EPO, ECP, EPX, and cytokines in ulcerative colitis and proctitis in segmental perfusion. Am. J. Gastroenterol.,  1999, 94(7), 1876-1883.
[http://dx.doi.org/10.1111/j.1572-0241.1999.01223.x] [PMID: 10406252] 
[141] 
Peterson, C.G.; Eklund, E.; Taha, Y.; Raab, Y.; Carlson, M. A new method for the quantification of neutrophil and eosinophil cationic proteins in feces: establishment of normal levels and clinical application in patients with inflammatory bowel disease. Am. J. Gastroenterol.,  2002, 97(7), 1755-1762.
[http://dx.doi.org/10.1111/j.1572-0241.2002.05837.x] [PMID: 12135031] 
[142] 
Desai, M.P.; Labhasetwar, V.; Amidon, G.L.; Levy, R.J. Gastrointestinal uptake of biodegradable microparticles: effect of particle size. Pharm. Res.,  1996, 13(12), 1838-1845.
[http://dx.doi.org/10.1023/A:1016085108889] [PMID: 8987081] 
[143] 
Morigi, V.; Tocchio, A.; Bellavite Pellegrini, C.; Sakamoto, J.H.; Arnone, M.; Tasciotti, E. Nanotechnology in medicine: from inception to market domination. J. Drug Deliv.,  2012, 2012 389485
[http://dx.doi.org/10.1155/2012/389485] [PMID: 22506121] 
[144] 
Hillyer, J.F.; Albrecht, R.M. Gastrointestinal persorption and tissue distribution of differently sized colloidal gold nanoparticles. J. Pharm. Sci.,  2001, 90(12), 1927-1936.
[http://dx.doi.org/10.1002/jps.1143] [PMID: 11745751] 
[145] 
Jani, P.; Halbert, G.W.; Langridge, J.; Florence, A.T. The uptake and translocation of latex nanospheres and microspheres after oral administration to rats. J. Pharm. Pharmacol.,  1989, 41(12), 809-812.
[http://dx.doi.org/10.1111/j.2042-7158.1989.tb06377.x] [PMID: 2576440] 
[146] 
Walczak, A.P.; Hendriksen, P.J.M.; Woutersen, R.A.; van der Zande, M.; Undas, A.K.; Helsdingen, R.; van den Berg, H.H.; Rietjens, I.M.; Bouwmeester, H. Bioavailability and biodistribution of differently charged polystyrene nanoparticles upon oral exposure in rats. J. Nanopart. Res.,  2015, 17(5), 231.
[http://dx.doi.org/10.1007/s11051-015-3029-y] [PMID: 26028989] 
[147] 
Hillery, A.M.; Jani, P.U.; Florence, A.T. Comparative, quantitative study of lymphoid and non-lymphoid uptake of 60 nm polystyrene particles. J. Drug Target.,  1994, 2(2), 151-156.
[http://dx.doi.org/10.3109/10611869409015904] [PMID: 8069593] 
[148] 
Hoet, P.H.; Brüske-Hohlfeld, I.; Salata, O.V. Nanoparticles - known and unknown health risks. J. Nanobiotechnology,  2004, 2(1), 12.
[http://dx.doi.org/10.1186/1477-3155-2-12] [PMID: 15588280] 
[149] 
Pachuau, L.; Mazumder, B. Colonic drug delivery systems based on natural polysaccharides and their evaluation. Mini Rev. Med. Chem.,  2013, 13(13), 1982-1991.
[http://dx.doi.org/10.2174/13895575113136660085] [PMID: 24032514] 
[150] 
Si, X.Y.; Merlin, D.; Xiao, B. Recent advances in orally administered cell-specific nanotherapeutics for inflammatory bowel disease. World J. Gastroenterol.,  2016, 22(34), 7718-7726.
[http://dx.doi.org/10.3748/wjg.v22.i34.7718] [PMID: 27678353] 
[151] 
Navarro, G.; Tros de Ilarduya, C. Activated and non-activated PAMAM dendrimers for gene delivery in vitro and in vivo. Nanomedicine (Lond.),  2009, 5(3), 287-297.
[http://dx.doi.org/10.1016/j.nano.2008.12.007] [PMID: 19523431] 
[152] 
Wiwattanapatapee, R.; Lomlim, L.; Saramunee, K. Dendrimers conjugates for colonic delivery of 5-aminosalicylic acid. J. Control. Release,  2003, 88(1), 1-9.
[http://dx.doi.org/10.1016/S0168-3659(02)00461-3] [PMID: 12586498] 
[153] 
Gou, M.; Men, K.; Shi, H.; Xiang, M.; Zhang, J.; Song, J.; Long, J.; Wan, Y.; Luo, F.; Zhao, X.; Qian, Z. Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo. Nanoscale,  2011, 3(4), 1558-1567.
[http://dx.doi.org/10.1039/c0nr00758g] [PMID: 21283869] 
[154] 
Bromberg, L. Intelligent hydrogels for the oral delivery of chemotherapeutics. Expert Opin. Drug Deliv.,  2005, 2(6), 1003-1013.
[http://dx.doi.org/10.1517/17425247.2.6.1003] [PMID: 16296805] 
[155] 
Garg, A.; Kokkoli, E. pH-Sensitive PEGylated liposomes functionalized with a fibronectin-mimetic peptide show enhanced intracellular delivery to colon cancer cell. Curr. Pharm. Biotechnol.,  2011, 12(8), 1135-1143.
[http://dx.doi.org/10.2174/138920111796117328] [PMID: 21470144] 
[156] 
Riviere, K.; Kieler-Ferguson, H.M.; Jerger, K.; Szoka, F.C., Jr Anti-tumor activity of liposome encapsulated fluoroorotic acid as a single agent and in combination with liposome irinotecan. J. Control. Release,  2011, 153(3), 288-296.
[http://dx.doi.org/10.1016/j.jconrel.2011.05.005] [PMID: 21600250] 
[157] 
Lee, S.M.; Kim, H.J.; Ha, Y.J.; Park, Y.N.; Lee, S.K.; Park, Y.B.; Yoo, K.H. Targeted chemo-photothermal treatments of rheumatoid arthritis using gold half-shell multifunctional nanoparticles. ACS Nano,  2013, 7(1), 50-57.
[158] 
Ilinskaya, A.N.; Dobrovolskaia, M.A. Immunosuppressive and anti-inflammatory properties of engineered nanomaterials. Br. J. Pharmacol.,  2014, 171(17), 3988-4000.
[http://dx.doi.org/10.1111/bph.12722] [PMID: 24724793] 
[159] 
Oliveira, I.M.; Gonçalves, C.; Reis, R.L.; Oliveira, J.M. Engineering nanoparticles for targeting rheumatoid arthritis: Past, present, and future trends. Nano Res.,  2018, 11(9), 4489-4506.
[http://dx.doi.org/10.1007/s12274-018-2071-3] 
[160] 
Landriscina, A.; Rosen, J.; Friedman, A. Nanotechnology, inflammation and the skin barrier: Innovative approaches for skin health and cosmesis. Cosmetics,  2015, 2(2), 177-186.
[http://dx.doi.org/10.3390/cosmetics2020177] 
[161] 
Yokota, J.; Kyotani, S. Influence of nanoparticle size on the skin penetration, skin retention and anti-inflammatory activity of non-steroidal anti-inflammatory drugs. J. Chin. Med. Ass.,  2018, 81(6), 511-519.
[http://dx.doi.org/10.1016/j.jcma.2018.01.008] 
[162] 
Jawahar, N.; Meyyanathan, S.N. Polymeric nanoparticles for drug delivery and targeting: A comprehensive review. Int. J. Health Allied Sci.,  2012, 1(4), 217-233.
[http://dx.doi.org/10.4103/2278-344X.107832] 
[163] 
Dar, M.J.; Ali, H.; Khan, A.; Khan, G.M. Polymer-based drug delivery: the quest for local targeting of inflamed intestinal mucosa. J. Drug Target.,  2017, 25(7), 582-596.
[http://dx.doi.org/10.1080/1061186X.2017.1298601] [PMID: 28277824] 
[164] 
Hejazi, R.; Amiji, M. Chitosan-based gastrointestinal delivery systems. J. Control. Release,  2003, 89(2), 151-165.
[http://dx.doi.org/10.1016/S0168-3659(03)00126-3] [PMID: 12711440] 
[165] 
Ballar_ın-Gonz_alez, B.; Dagnaes-Hansen, F.; Fenton, R.A.; Gao, S; Hein, S.; Dong, M.; Kjems, J.; Howard, K.A. Protection and systemic translocation of siRNA following oral administration of chitosan/siRNA nanoparticles. Mol. Ther. Nucleic Acids,  2013, 2 e76
[http://dx.doi.org/10.1038/mtna.2013.2] 
[166] 
Danhier, F.; Ansorena, E.; Silva, J.M.; Coco, R.; Le Breton, A.; Préat, V. PLGA-based nanoparticles: an overview of biomedical applications. J. Control. Release,  2012, 161(2), 505-522.
[http://dx.doi.org/10.1016/j.jconrel.2012.01.043] [PMID: 22353619] 
[167] 
Vert, M.; Mauduit, J.; Li, S. Biodegradation of PLA/GA polymers: increasing complexity. Biomaterials,  1994, 15(15), 1209-1213.
[http://dx.doi.org/10.1016/0142-9612(94)90271-2] [PMID: 7703316] 
[168] 
Thakral, S.; Thakral, N.K.; Majumdar, D.K. Eudragit: a technology evaluation. Expert Opin. Drug Deliv.,  2013, 10(1), 131-149.
[http://dx.doi.org/10.1517/17425247.2013.736962] [PMID: 23102011] 
[169] 
Ibekwe, V.C.; Liu, F.; Fadda, H.M.; Khela, M.K.; Evans, D.F.; Parsons, G.E.; Basit, A.W. An investigation into the in vivo performance variability of pH responsive polymers for ileo-colonic drug delivery using gamma scintigraphy in humans. J. Pharm. Sci.,  2006, 95(12), 2760-2766.
[http://dx.doi.org/10.1002/jps.20742] [PMID: 16917845] 
[170] 
Singla, A.K.; Chawla, M.; Singh, A. Potential applications of carbomer in oral mucoadhesive controlled drug delivery system: a review. Drug Dev. Ind. Pharm.,  2000, 26(9), 913-924.
[http://dx.doi.org/10.1081/DDC-100101318] [PMID: 10914315] 
[171] 
Leopold, C.S.; Eikeler, D. Eudragit E as coating material for the pH-controlled drug release in the topical treatment of inflammatory bowel disease (IBD). J. Drug Target.,  1998, 6(2), 85-94.
[http://dx.doi.org/10.3109/10611869808997884] [PMID: 9886233] 
[172] 
Meissner, Y.; Pellequer, Y.; Lamprecht, A. Nanoparticles in inflammatory bowel disease: particle targeting versus pH-sensitive delivery. Int. J. Pharm.,  2006, 316(1-2), 138-143.
[http://dx.doi.org/10.1016/j.ijpharm.2006.01.032] [PMID: 16675176] 
[173] 
Laroui, H.; Sitaraman, S.V.; Merlin, D. Gastrointestinal delivery of anti-inflammatory nanoparticles. Methods Enzymol.,  2012, 509, 101-125.
[http://dx.doi.org/10.1016/B978-0-12-391858-1.00006-X] [PMID: 22568903] 
[174] 
Lamprecht, A.; Yamamoto, H.; Takeuchi, H.; Kawashima, Y. Nanoparticles enhance therapeutic efficiency by selectively increased local drug dose in experimental colitis in rats. J. Pharmacol. Exp. Ther.,  2005, 315(1), 196-202.
[http://dx.doi.org/10.1124/jpet.105.088146] [PMID: 15980057] 
[175] 
Naeem, M.; Bae, J.; Oshi, M.A.; Kim, M-S.; Moon, H.R.; Lee, B.L.; Im, E.; Jung, Y.; Yoo, J.W. Colon-targeted delivery of cyclosporine A using dual-functional Eudragit® FS30D/PLGA nanoparticles ameliorates murine experimental colitis. Int. J. Nanomedicine,  2018, 13, 1225-1240.
[http://dx.doi.org/10.2147/IJN.S157566] [PMID: 29535519] 
[176] 
Lamprecht, A.; Yamamoto, H.; Takeuchi, H.; Kawashima, Y. A pH-sensitive microsphere system for the colon delivery of tacrolimus containing nanoparticles. J. Control. Release,  2005, 104(2), 337-346.
[http://dx.doi.org/10.1016/j.jconrel.2005.02.011] [PMID: 15907584] 
[177] 
Pertuit, D.; Moulari, B.; Betz, T.; Nadaradjane, A.; Neumann, D.; Ismaïli, L.; Refouvelet, B.; Pellequer, Y.; Lamprecht, A. 5-amino salicylic acid bound nanoparticles for the therapy of inflammatory bowel disease. J. Control. Release,  2007, 123(3), 211-218.
[http://dx.doi.org/10.1016/j.jconrel.2007.08.008] [PMID: 17889397] 
[178] 
Abhimanyu, S.; Greg, T. Therapeutic polymeric nanoparticles comprising corticosteroids and methods of making and using same. WO2011084518A2, July 14th, 2011. 
[179] 
Leonard, F.; Ali, H.; Collnot, E.M.; Crielaard, B.J.; Lammers, T.; Storm, G.; Lehr, C.M. Screening of budesonide nanoformulations for treatment of inflammatory bowel disease in an inflamed 3D cell-culture model. ALTEX,  2012, 29(3), 275-285.
[http://dx.doi.org/10.14573/altex.2012.3.275] [PMID: 22847255] 
[180] 
Ben, M.S.; Marina, K.; Mukund, G.S. Eudragit S-100 encapsulated chitosan coated liposomes containing prednisolone for colon targeting: In vitro, Ex vivo and In vivo Evaluation. J Young Pharm.,  2019, 11(1), 07-11.
[181] 
Safar, R.; Houlgatte, R.; Le Faou, A.; Ronzani, C.; Wu, W.; Ferrari, L.; Dubois-Pot-Schneider, H.; Rihn, B.H.; Joubert, O. Encapsulation of S-nitrosoglutathione: a transcriptomic validation. Drug Dev. Ind. Pharm.,  2019, 45(3), 423-429.
[http://dx.doi.org/10.1080/03639045.2018.1546313] [PMID: 30449192] 
[182] 
Bertoni, S.; Liu, Z.; Correia, A.; Martins, J.P.; Rahikkala, A.; Fontana, F.; Marianna Kemell, M.; Liu, D.; Albertini, B.; Passerini, N.; Li, W.; Santos, H.A. pH and reactive oxygen species-sequential responsive nano-in-micro composite for targeted therapy of inflammatory bowel disease. Adv. Funct. Mater.,  2018, 28(50) 1806175
[http://dx.doi.org/10.1002/adfm.201806175] 
[183] 
Wang, X.; Yan, J-J.; Wang, L.; Pan, D.; Yang, R.; Xu, Y.; Sheng, J.; Huang, Q.; Zhao, H.; Yang, M. Rational design of polyphenol-poloxamer nanovesicles for targeting inflammatory bowel disease therapy. Chem. Mater.,  2018, 30(12), 4073-4080.
[http://dx.doi.org/10.1021/acs.chemmater.8b01173] 
[184] 
Gardlik, R.; Palffy, R.; Celec, P. Recombinant probiotic therapy in experimental colitis in mice. Folia Biol. (Praha),  2012, 58(6), 238-245.
[PMID: 23438849] 
[185] 
Shanahan, F. Turbo probiotics for IBD. Gastroenterology,  2001, 120(5), 1297-1298.
[http://dx.doi.org/10.1016/S0016-5085(01)87910-5] [PMID: 11266396] 
[186] 
Martín, R.; Chain, F.; Miquel, S.; Natividad, J.M.; Sokol, H.; Verdu, E.F.; Langella, P.; Bermúdez-Humarán, L.G.; Bermúdez-Humarán, L.G. Effects in the use of a genetically engineered strain of Lactococcus lactis delivering in situ IL-10 as a therapy to treat low-grade colon inflammation. Hum. Vaccin. Immunother.,  2014, 10(6), 1611-1621.
[http://dx.doi.org/10.4161/hv.28549] [PMID: 24732667] 
[187] 
Chau, L-Y. Heme oxygenase-1: emerging target of cancer therapy. J. Biomed. Sci.,  2015, 22(22)
[http://dx.doi.org/10.1186/s12929-015-0128-0] [PMID: 25885228] 
[188] 
Bermúdez-Humarán, L.G.; Motta, J-P.; Aubry, C.; Kharrat, P.; Rous-Martin, L.; Sallenave, J-M.; Deraison, C.; Vergnolle, N.; Langella, P. Serine protease inhibitors protect better than IL-10 and TGF-β anti-inflammatory cytokines against mouse colitis when delivered by recombinant lactococci. Microb. Cell Fact.,  2015, 14(1), 26.
[http://dx.doi.org/10.1186/s12934-015-0198-4] [PMID: 25889561] 
[189] 
Vandenbroucke, K.; de Haard, H.; Beirnaert, E.; Dreier, T.; Lauwereys, M.; Huyck, L.; Van Huysse, J.; Demetter, P.; Steidler, L.; Remaut, E.; Cuvelier, C.; Rottiers, P. Orally administered L. lactis secreting an anti-TNF Nanobody demonstrate efficacy in chronic colitis. Mucosal Immunol.,  2010, 3(1), 49-56.
[http://dx.doi.org/10.1038/mi.2009.116] [PMID: 19794409] 
[190] 
Lothar, S.; Pieter, R.; Erik, R. Self-containing lactobacillus strain comprising a thya mutation and therapeutic applications thereof. CA2506031A1, 3rd June, 2004. 
[191] 
Xiao, B.; Chen, Q.; Zhang, Z.; Wang, L.; Kang, Y.; Denning, T.; Merlin, D. TNFα gene silencing mediated by orally targeted nanoparticles combined with interleukin-22 for synergistic combination therapy of ulcerative colitis. J. Control. Release,  2018, 287, 235-246.
[http://dx.doi.org/10.1016/j.jconrel.2018.08.021] [PMID: 30107214] 
[192] 
Peer, D.; Park, E.J.; Morishita, Y.; Carman, C.V.; Shimaoka, M. Systemic leukocyte-directed siRNA delivery revealing cyclin D1 as an anti-inflammatory target. Science,  2008, 319(5863), 627-630.
[http://dx.doi.org/10.1126/science.1149859] [PMID: 18239128] 
[193] 
Liechty, W.B.; Scheuerle, R.L.; Vela Ramirez, J.E.; Peppas, N.A. Cytoplasmic delivery of functional siRNA using pH-Responsive nanoscale hydrogels. Int. J. Pharm.,  2019, 562, 249-257.
[http://dx.doi.org/10.1016/j.ijpharm.2019.03.013] [PMID: 30858114] 
[194] 
Pitto-Barry, A.; Lupan, A.; Saidykhan, A.; Zegke, M.; Swift, T.; Attia, A.A.A.; Lord, R.M.; Barry, N.P.E. Pseudo electron-deficient organometallics: limited reactivity towards electron-donating ligands. Dalton Trans.,  2017, 46(45), 15676-15683.
[http://dx.doi.org/10.1039/C7DT02827J] [PMID: 28926052] 
[195] 
Zhang, J.; Pitto-Barry, A.; Shang, L.; Barry, N.P.E. Anti-inflammatory activity of electron-deficient organometallics. R. Soc. Open Sci.,  2017, 4(11) 170786
[http://dx.doi.org/10.1098/rsos.170786] [PMID: 29291071] 
[196] 
Yin, H.; Fang, J.; Liao, L.; Nakamura, H.; Maeda, H. Styrene-maleic acid copolymer-encapsulated CORM2, a water-soluble carbon monoxide (CO) donor with a constant CO-releasing property, exhibits therapeutic potential for inflammatory bowel disease. J. Control. Release,  2014, 187, 14-21.
[http://dx.doi.org/10.1016/j.jconrel.2014.05.018] [PMID: 24852097] 
[197] 
Furfaro, F.; Bezzio, C.; Ardizzone, S.; Massari, A.; de Franchis, R.; Maconi, G. Overview of biological therapy in ulcerative colitis: current and future directions. J. Gastrointestin. Liver Dis.,  2015, 24(2), 203-213.
[PMID: 26114181] 
[198] 
Conner, E.M.; Reglinski, J.; Smith, W.E.; Zeitlin, I.J. Schiff base complexes of copper and zinc as potential anti-colitic compounds. Biometals,  2017, 30(3), 423-439.
[http://dx.doi.org/10.1007/s10534-017-0016-z] [PMID: 28425040] 
[199] 
Itagaki, M.; Saruta, M.; Saijo, H.; Mitobe, J.; Arihiro, S.; Matsuoka, M.; Kato, T.; Ikegami, M.; Tajiri, H. Efficacy of zinc-carnosine chelate compound, Polaprezinc, enemas in patients with ulcerative colitis. Scand. J. Gastroenterol.,  2014, 49(2), 164-172.
[http://dx.doi.org/10.3109/00365521.2013.863963] [PMID: 24286534] 
[200] 
Galli, S.J.; Tsai, M.; Piliponsky, A.M. The development of allergic inflammation. Nature,  2008, 454(7203), 445-454.
[http://dx.doi.org/10.1038/nature07204] [PMID: 18650915] 
[201] 
Nadworny, P.L.; Wang, J.; Tredget, E.E.; Burrell, R.E. Anti-inflammatory activity of nanocrystalline silver in a porcine contact dermatitis model. Nanomedicine (Lond.),  2008, 4(3), 241-251.
[http://dx.doi.org/10.1016/j.nano.2008.04.006] [PMID: 18550449] 
[202] 
Bhol, K.C.; Schechter, P.J. Effects of nanocrystalline silver (NPI 32101) in a rat model of ulcerative colitis. Dig. Dis. Sci.,  2007, 52(10), 2732-2742.
[http://dx.doi.org/10.1007/s10620-006-9738-4] [PMID: 17436088] 
[203] 
O’Sullivan, S.; Gilmer, J.F.; Medina, C. Matrix metalloproteinases in inflammatory bowel disease: an update. Mediators Inflamm.,  2015, 2015 964131
[http://dx.doi.org/10.1155/2015/964131] [PMID: 25948887] 
[204] 
Siczek, K.; Zatorski, H.; Chmielowiec-Korzeniowska, A.; Kordek, R.; Tymczyna, L.; Fichna, J. Evaluation of anti-inflammatory effect of silver-coated glass beads in mice with experimentally induced colitis as a new type of treatment in inflammatory bowel disease. Pharmacol. Rep.,  2017, 69, 386-392.
[http://dx.doi.org/10.1016/j.pharep.2017.01.003] 
[205] 
Leung, C-H.; Lin, S.; Zhong, H-J.; Ma, D-L. Metal complexes as potential modulators of inflammatory and autoimmune responses. Chem. Sci. (Camb.),  2015, 6(2), 871-884.
[http://dx.doi.org/10.1039/C4SC03094J] [PMID: 28660015] 
[206] 
Kupcewicz, B.; Sobiesiak, K.; Malinowska, K.; Koprowska, K.; Czyz, M.; Keppler, B.; Budzisz, E. Copper(II) complexes with derivatives of pyrazole as potential antioxidant enzyme mimics. Med. Chem. Res.,  2013, 22(5), 2395-2402.
[http://dx.doi.org/10.1007/s00044-012-0233-5] [PMID: 23542890] 
[207] 
Hussein, R.M.; Saleh, H. Promising therapeutic effect of gold nanoparticles against dinitrobenzene sulfonic acid-induced colitis in rats. Nanomedicine (Lond.), 2018.
[http://dx.doi.org/10.2217/nnm-2018-0009] [PMID: 30085904] 
[208] 
Zhong, H-J.; Wang, W.; Kang, T-S.; Yan, H.; Yang, Y.; Xu, L.; Wang, Y.; Ma, D-L.; Leung, C-H.A. A rhodium(iii) complex as an inhibitor of neural precursor cell expressed, developmentally down-regulated 8-activating enzyme with in vivo activity against inflammatory bowel disease. J. Med. Chem.,  2017, 60(1), 497-503.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00250] [PMID: 27976900] 
[209] 
Li, J.; Chen, H.; Wang, B.; Cai, C.; Yang, X.; Chai, Z.; Feng, W. ZnO nanoparticles act as supportive therapy in DSS-induced ulcerative colitis in mice by maintaining gut homeostasis and activating Nrf2 signaling. Sci. Rep.,  2017, 7(1) 43126
[210] 
Vandenbroucke, F.; Mortelé, K.J.; Tatli, S.; Pelsser, V.; Erturk, S.M.; De Mey, J.; Silverman, S.G. Noninvasive multidetector computed tomography enterography in patients with small-bowel Crohn’s disease: is a 40-second delay better than 70 seconds? Acta Radiol.,  2007, 48(10), 1052-1060.
[http://dx.doi.org/10.1080/02841850701589290] [PMID: 17963078] 
[211] 
Paulsen, S.R.; Huprich, J.E.; Fletcher, J.G.; Booya, F.; Young, B.M.; Fidler, J.L.; Johnson, C.D.; Barlow, J.M.; Earnest, F., IV CT enterography as a diagnostic tool in evaluating small bowel disorders: review of clinical experience with over 700 cases. Radiographics,  2006, 26(3), 641-657.
[http://dx.doi.org/10.1148/rg.263055162] [PMID: 16702444] 
[212] 
Choi, D.; Jin Lee, S.; Ah Cho, Y.; Lim, H.K.; Hoon Kim, S.; Jae Lee, W.; Hoon Lim, J.; Park, H.; Rae Lee, Y. Bowel wall thickening in patients with Crohn’s disease: CT patterns and correlation with inflammatory activity. Clin. Radiol.,  2003, 58(1), 68-74.
[http://dx.doi.org/10.1053/crad.2002.1068] [PMID: 12565208] 
[213] 
Paulsen, S.R.; Huprich, J.E.; Hara, A.K. CT enterography: noninvasive evaluation of Crohn’s disease and obscure gastrointestinal bleed. Radiol. Clin. North Am.,  2007, 45(2), 303-315.
[http://dx.doi.org/10.1016/j.rcl.2007.03.009] [PMID: 17502219] 
[214] 
Hassan, C.; Cerro, P.; Zullo, A.; Spina, C.; Morini, S. Computed tomography enteroclysis in comparison with ileoscopy in patients with Crohn’s disease. Int. J. Colorectal Dis.,  2003, 18(2), 121-125.
[http://dx.doi.org/10.1007/s00384-002-0455-y] [PMID: 12548413] 
[215] 
Schreyer, A.G.; Scheibl, K.; Heiss, P.; Feuerbach, S.; Seitz, J.; Herfarth, H. MR colonography in inflammatory bowel disease. Abdom. Imaging,  2006, 31(3), 302-307.
[http://dx.doi.org/10.1007/s00261-005-0377-6] [PMID: 16447093] 
[216] 
Yoon, K.; Chang, K-T.; Lee, H.J. MRI for crohn’s disease: present and future. BioMed Res. Int.,  2015, 2015 786802
[http://dx.doi.org/10.1155/2015/786802] [PMID: 26413543] 
[217] 
Sargsyan, S.A.; Thurman, J.M. Molecular imaging of autoimmune diseases and inflammation. Mol. Imaging,  2012, 11(3), 251-264.
[http://dx.doi.org/10.2310/7290.2011.00045] [PMID: 22554489] 
[218] 
Gaglia, J.L.; Guimaraes, A.R.; Harisinghani, M.; Turvey, S.E.; Jackson, R.; Benoist, C.; Mathis, D.; Weissleder, R. Noninvasive imaging of pancreatic islet inflammation in type 1A diabetes patients. J. Clin. Invest.,  2011, 121(1), 442-445.
[http://dx.doi.org/10.1172/JCI44339] [PMID: 21123946] 
[219] 
Deepak, P.; Fowler, K.J.; Fletcher, J.G.; Bruining, D.H. Novel imaging approaches in inflammatory bowel diseases. Inflamm. Bowel Dis.,  2018, 25(2), 248-260.
[http://dx.doi.org/10.1093/ibd/izy239] [PMID: 30010908] 
[220] 
Atreya, R.; Neumann, H.; Neufert, C.; Waldner, M.J.; Billmeier, U.; Zopf, Y.; Willma, M.; App, C.; Münster, T.; Kessler, H.; Maas, S.; Gebhardt, B.; Heimke-Brinck, R.; Reuter, E.; Dörje, F.; Rau, T.T.; Uter, W.; Wang, T.D.; Kiesslich, R.; Vieth, M.; Hannappel, E.; Neurath, M.F. In vivo imaging using fluorescent antibodies to tumor necrosis factor predicts therapeutic response in Crohn’s disease. Nat. Med.,  2014, 20(3), 313-318.
[http://dx.doi.org/10.1038/nm.3462] [PMID: 24562382] 
[221] 
Rath, T.; Bojarski, C.; Neurath, M.F.; Atreya, R. Molecular imaging of mucosal α4β7 integrin expression with the fluorescent anti-adhesion antibody vedolizumab in Crohn’s disease. Gastrointest. Endosc.,  2017, 86(2), 406-408.
[http://dx.doi.org/10.1016/j.gie.2017.01.012] [PMID: 28137597] 
[222] 
Xu, X.; An, H.; Zhang, D.; Tao, H.; Dou, Y.; Li, X.; Huang, J.; Zhang, J. A self-illuminating nanoparticle for inflammation imaging and cancer therapy. Sci. Adv.,  2019, 5 eaat2953
[http://dx.doi.org/10.1126/sciadv.aat2953] 
[223] 
Hussain, S.M.; Hess, K.L.; Gearhart, J.M.; Geiss, K.T.; Schlager, J.J. In vitro toxicity of nanoparticles in BRL 3A rat liver cells. Toxicol. In Vitro,  2005, 19(7), 975-983.
[http://dx.doi.org/10.1016/j.tiv.2005.06.034] [PMID: 16125895] 
[224] 
Bakand, S.; Hayes, A. Toxicological considerations, toxicity assessment, and risk management of inhaled nanoparticles. Int. J. Mol. Sci.,  2016, 17(6), 929.
[http://dx.doi.org/10.3390/ijms17060929] [PMID: 27314324] 
[225] 
Song, Y.; Li, X.; Du, X. Exposure to nanoparticles is related to pleural effusion, pulmonary fibrosis and granuloma. Eur. Respir. J.,  2009, 34(3), 559-567.
[http://dx.doi.org/10.1183/09031936.00178308] [PMID: 19696157] 
[226] 
Rinaldo, M.; Andujar, P.; Lacourt, A.; Martinon, L.; Canal Raffin, M.; Dumortier, P.; Pairon, J.C.; Brochard, P. Perspectives in biological monitoring of inhaled nanosized particles. Ann. Occup. Hyg.,  2015, 59(6), 669-680.
[http://dx.doi.org/10.1093/annhyg/mev015] [PMID: 25795003] 
[227] 
Oberdorster, G.; Kane, A.B.; Klaper, R.D.; Hurt, R.H. Nanotoxicology.Casarett and Doull’s Toxicology—The Basic Science of Poisons; Klaassen, C.D., Ed.; McGraw Hill: New York, 2013, pp. 1189-1229.
[228] 
Sutherland, W.J.; Clout, M.; Côté, I.M.; Daszak, P.; Depledge, M.H.; Fellman, L.; Fleishman, E.; Garthwaite, R.; Gibbons, D.W.; De Lurio, J.; Impey, A.J.; Lickorish, F.; Lindenmayer, D.; Madgwick, J.; Margerison, C.; Maynard, T.; Peck, L.S.; Pretty, J.; Prior, S.; Redford, K.H.; Scharlemann, J.P.; Spalding, M.; Watkinson, A.R. A horizon scan of global conservation issues for 2010. Trends Ecol. Evol. (Amst.),  2010, 25(1), 1-7.
[http://dx.doi.org/10.1016/j.tree.2009.10.003] [PMID: 19939492] 
[229] 
Ali, H.; Weigmann, B.; Collnot, E.M.; Khan, S.A.; Windbergs, M.; Lehr, C.M. Budesonide loaded PLGA nanoparticles for targeting the inflamed intestinal mucosa--pharmaceutical characterization and fluorescence imaging. Pharm. Res.,  2016, 33(5), 1085-1092.
[http://dx.doi.org/10.1007/s11095-015-1852-6] [PMID: 26718953] 
[230] 
Iqbal, S.; Du, X.; Wang, J.; Li, H.; Yuan, Y.; Wang, J. Surface charge tunable nanoparticles for TNF-α siRNA oral delivery for treating ulcerative colitis. Nano Res.,  2018, 11(5), 2872-2884.
[http://dx.doi.org/10.1007/s12274-017-1918-3] 
[231] 
Laroui, H.; Theiss, A.L.; Yan, Y.; Dalmasso, G.; Nguyen, H.T.T.; Sitaraman, S.V.; Merlin, D. Functional TNFα gene silencing mediated by polyethyleneimine/TNFα siRNA nanocomplexes in inflamed colon. Biomaterials,  2011, 32(4), 1218-1228.
[http://dx.doi.org/10.1016/j.biomaterials.2010.09.062] [PMID: 20970849] 
[232] 
Kriegel, C.; Amiji, M. Oral TNF-α gene silencing using a polymeric microsphere-based delivery system for the treatment of inflammatory bowel disease. J. Control. Release,  2011, 150(1), 77-86.
[http://dx.doi.org/10.1016/j.jconrel.2010.10.002] [PMID: 20959130] 
[233] 
Xiao, B.; Laroui, H.; Ayyadurai, S.; Viennois, E.; Charania, M.A.; Zhang, Y.; Merlin, D. Mannosylated bioreducible nanoparticle-mediated macrophage-specific TNF-α RNA interference for IBD therapy. Biomaterials,  2013, 34(30), 7471-7482.
[http://dx.doi.org/10.1016/j.biomaterials.2013.06.008] [PMID: 23820013] 
[234] 
Xiao, B.; Zhang, Z.; Viennois, E.; Kang, Y.; Zhang, M.; Han, M.K.; Chen, J.; Merlin, D. Combination therapy for ulcerative colitis: orally targeted nanoparticles prevent mucosal damage and relieve inflammation. Theranostics,  2016, 6(12), 2250-2266.
[http://dx.doi.org/10.7150/thno.15710] [PMID: 27924161] 
[235] 
Frede, A. Modulation of inflammatory responses at mucosal surfaces by nanoparticle-based sirna delivery. Available from:. https://www.research.manchester.ac.uk/portal/en/theses/modulation-of-inflammatory-responses-at-mucosal-surfaces-by-nanoparticlebased-sirna-delivery(188e5303-0b29-4d14-8635-7d1fcf448270).html  (Accessed 2016).
[236] 
Kriegel, C.; Amiji, M.M. Dual TNF-α/cyclin D1 gene silencing with an oral polymeric microparticle system as a novel strategy for the treatment of inflammatory bowel disease. Clin. Transl. Gastroenterol.,  2011, 2(3), e2-e2.
[http://dx.doi.org/10.1038/ctg.2011.1] [PMID: 23237848] 
[237] 
Knipe, J.M.; Strong, L.E.; Peppas, N.A. Enzyme- and pH-responsive microencapsulated nanogels for oral delivery of siRNA to induce TNF-α knockdown in the intestine. Biomacromolecules,  2016, 17(3), 788-797.
[http://dx.doi.org/10.1021/acs.biomac.5b01518] [PMID: 26813877] 
[238] 
Fukata, T.; Mizushima, T.; Nishimura, J.; Okuzaki, D.; Wu, X.; Hirose, H.; Yokoyama, Y.; Kubota, Y.; Nagata, K.; Tsujimura, N.; Inoue, A.; Miyoshi, N.; Haraguchi, N.; Takahashi, H.; Hata, T.; Matsuda, C.; Kayama, H.; Takeda, K.; Doki, Y.; Mori, M.; Yamamoto, H. The supercarbonate apatite-microrna complex inhibits dextran sodium sulfate-induced colitis. Mol. Ther. Nucleic Acids,  2018, 12, 658-671.
[http://dx.doi.org/10.1016/j.omtn.2018.07.007] [PMID: 30092402] 
[239] 
Aouadi, M.; Tesz, G.J.; Nicoloro, S.M.; Wang, M.; Chouinard, M.; Soto, E.; Ostroff, G.R.; Czech, M.P. Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation. Nature,  2009, 458(7242), 1180-1184.
[http://dx.doi.org/10.1038/nature07774] [PMID: 19407801] 
[240] 
Ball, R.L.; Knapp, C.M.; Whitehead, K.A. Lipidoid nanoparticles for siRNA delivery to the intestinal epithelium: in vitro investigations in a caco-2 model. PLoS One,  2015, 10(7) e0133154
[http://dx.doi.org/10.1371/journal.pone.0133154] [PMID: 26192592] 
[241] 
Tahara, K.; Samura, S.; Tsuji, K.; Yamamoto, H.; Tsukada, Y.; Bando, Y.; Tsujimoto, H.; Morishita, R.; Kawashima, Y. Oral nuclear factor-κB decoy oligonucleotides delivery system with chitosan modified poly(D,L-lactide-co-glycolide) nanospheres for inflammatory bowel disease. Biomaterials,  2011, 32(3), 870-878.
[http://dx.doi.org/10.1016/j.biomaterials.2010.09.034] [PMID: 20934748] 
[242] 
Steidler, L.; Hans, W.; Schotte, L.; Neirynck, S.; Obermeier, F.; Falk, W.; Fiers, W.; Remaut, E. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science,  2000, 289(5483), 1352-1355.
[http://dx.doi.org/10.1126/science.289.5483.1352] [PMID: 10958782] 
[243] 
Nakase, H.; Okazaki, K.; Tabata, Y.; Ozeki, M.; Watanabe, N.; Ohana, M.; Uose, S.; Uchida, K.; Nishi, T.; Mastuura, M.; Tamaki, H.; Itoh, T.; Kawanami, C.; Chiba, T. New cytokine delivery system using gelatin microspheres containing interleukin-10 for experimental inflammatory bowel disease. J. Pharmacol. Exp. Ther.,  2002, 301(1), 59-65.
[http://dx.doi.org/10.1124/jpet.301.1.59] [PMID: 11907157] 
[244] 
Bhavsar, M.D.; Amiji, M.M. Oral IL-10 gene delivery in a microsphere-based formulation for local transfection and therapeutic efficacy in inflammatory bowel disease. Gene Ther.,  2008, 15(17), 1200-1209.
[http://dx.doi.org/10.1038/gt.2008.67] [PMID: 18418416] 
[245] 
Yavvari, P.S.; Verma, P.; Mustfa, S.A.; Pal, S.; Kumar, S.; Awasthi, A.K.; Ahuja, V.; Srikanth, C.V.; Srivastava, A.; Bajaj, A. A nanogel based oral gene delivery system targeting SUMOylation machinery to combat gut inflammation. Nanoscale,  2019, 11(11), 4970-4986.
[http://dx.doi.org/10.1039/C8NR09599J] [PMID: 30839018] 
[246] 
Kono, Y.; Iwasaki, A.; Matsuoka, K.; Fujita, T. Effect of mechanical agitation on cationic liposome transport across an unstirred water layer in caco-2 cells. Biol. Pharm. Bull.,  2016, 39(8), 1293-1299.
[http://dx.doi.org/10.1248/bpb.b16-00050] [PMID: 27476939] 
[247] 
Jain, S.; Amiji, M. Tuftsin-modified alginate nanoparticles as a noncondensing macrophage-targeted DNA delivery system. Biomacromolecules,  2012, 13(4), 1074-1085.
[http://dx.doi.org/10.1021/bm2017993] [PMID: 22385328] 
[248] 
Capurso, N.A.; Fahmy, T.M. Development of a pH-responsive particulate drug delivery vehicle for localized biologic therapy in inflammatory bowel disease. Yale J. Biol. Med.,  2011, 84(3), 285-288.
[PMID: 21966047] 
[249] 
Theiss, A.L.; Laroui, H.; Obertone, T.S.; Chowdhury, I.; Thompson, W.E.; Merlin, D.; Sitaraman, S.V. Nanoparticle-based therapeutic delivery of prohibitin to the colonic epithelial cells ameliorates acute murine colitis. Inflamm. Bowel Dis.,  2011, 17(5), 1163-1176.
[http://dx.doi.org/10.1002/ibd.21469] [PMID: 20872832] 
[250] 
Mell, A. Interleukin-10-loaded nano-and microparticles for the local treatment of the intestinal mucosa and the deep lung. US9539217, 2017. 
[251] 
Xiao, B.; Xu, Z.; Viennois, E.; Zhang, Y.; Zhang, Z.; Zhang, M.; Han, M.K.; Kang, Y.; Merlin, D. Orally targeted delivery of tripeptide KPV via hyaluronic acid-functionalized nanoparticles efficiently alleviates ulcerative colitis. Mol. Ther.,  2017, 25(7), 1628-1640.
[http://dx.doi.org/10.1016/j.ymthe.2016.11.020] [PMID: 28143741] 
[252] 
Vandenbroucke, K.; Hans, W.; Van Huysse, J.; Neirynck, S.; Demetter, P.; Remaut, E.; Rottiers, P.; Steidler, L. Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice. Gastroenterology,  2004, 127(2), 502-513.
[http://dx.doi.org/10.1053/j.gastro.2004.05.020] [PMID: 15300583] 
[253] 
Laroui, H.; Dalmasso, G.; Nguyen, H.T.T.; Yan, Y.; Sitaraman, S.V.; Merlin, D. Drug-loaded nanoparticles targeted to the colon with polysaccharide hydrogel reduce colitis in a mouse model. Gastroenterology,  2010, 138(3), 843-53.e1, 2.
[http://dx.doi.org/10.1053/j.gastro.2009.11.003] [PMID: 19909746] 
[254] 
Kshirsagar, S.J.; Bhalekar, M.R.; Patel, J.N.; Mohapatra, S.K.; Shewale, N.S. Preparation and characterization of nanocapsules for colon-targeted drug delivery system. Pharm. Dev. Technol.,  2012, 17(5), 607-613.
[http://dx.doi.org/10.3109/10837450.2011.557732] [PMID: 21428704] 
[255] 
Tang, H.; Xiang, D.; Wang, F.; Mao, J.; Tan, X.; Wang, Y. 5-ASA-loaded SiO2 nanoparticles-a novel drug delivery system targeting therapy on ulcerative colitis in mice. Mol. Med. Rep.,  2017, 15(3), 1117-1122.
[http://dx.doi.org/10.3892/mmr.2017.6153] [PMID: 28138699] 
[256] 
Fukata, N.; Uchida, K.; Kusuda, T.; Koyabu, M.; Miyoshi, H.; Fukui, T.; Matsushita, M.; Nishio, A.; Tabata, Y.; Okazaki, K. The effective therapy of cyclosporine A with drug delivery system in experimental colitis. J. Drug Target.,  2011, 19(6), 458-467.
[http://dx.doi.org/10.3109/1061186X.2010.511224] [PMID: 20804404] 
[257] 
Nakase, H.; Okazaki, K.; Tabata, Y.; Uose, S.; Ohana, M.; Uchida, K.; Nishi, T.; Debreceni, A.; Itoh, T.; Kawanami, C.; Iwano, M.; Ikada, Y.; Chiba, T. An oral drug delivery system targeting immune-regulating cells ameliorates mucosal injury in trinitrobenzene sulfonic acid-induced colitis. J. Pharmacol. Exp. Ther.,  2001, 297(3), 1122-1128.
[PMID: 11356937] 
[258] 
Dianzani, C.; Foglietta, F.; Ferrara, B.; Rosa, A.C.; Muntoni, E.; Gasco, P.; Della Pepa, C.; Canaparo, R.; Serpe, L. Solid lipid nanoparticles delivering anti-inflammatory drugs to treat inflammatory bowel disease: Effects in an in vivo model. World J. Gastroenterol.,  2017, 23(23), 4200-4210.
[http://dx.doi.org/10.3748/wjg.v23.i23.4200] [PMID: 28694660] 
[259] 
Davoudi, Z.; Peroutka-Bigus, N.; Bellaire, B.; Wannemuehler, M.; Barrett, T.A.; Narasimhan, B.; Wang, Q. Intestinal organoids containing poly(lactic-co-glycolic acid) nanoparticles for the treatment of inflammatory bowel diseases. J. Biomed. Mater. Res. A,  2018, 106(4), 876-886.
[http://dx.doi.org/10.1002/jbm.a.36305] [PMID: 29226615] 
[260] 
Kim, J.K.; Garripelli, V.K.; Jeong, U.H.; Park, J.S.; Repka, M.A.; Jo, S. Novel pH-sensitive polyacetal-based block copolymers for controlled drug delivery. Int. J. Pharm.,  2010, 401(1-2), 79-86.
[http://dx.doi.org/10.1016/j.ijpharm.2010.08.029] [PMID: 20801203] 
[261] 
Makhlof, A.; Tozuka, Y.; Takeuchi, H. pH-Sensitive nanospheres for colon-specific drug delivery in experimentally induced colitis rat model. Eur. J. Pharm. Biopharm.,  2009, 72(1), 1-8.
[http://dx.doi.org/10.1016/j.ejpb.2008.12.013] [PMID: 19348015] 
[262] 
Kaur, S.; Narang, R.K.; Aggarwal, G. Formulation and development of colon-targeted mucopenetrating metronidazole nanoparticles. Trop. J. Pharm. Res.,  2017, 16(5), 967.
[http://dx.doi.org/10.4314/tjpr.v16i5.1] 
[263] 
Beloqui, A.; Coco, R.; Alhouayek, M.; Solinís, M.Á.; Rodríguez-Gascón, A.; Muccioli, G.G.; Préat, V. Budesonide-loaded nanostructured lipid carriers reduce inflammation in murine DSS-induced colitis. Int. J. Pharm.,  2013, 454(2), 775-783.
[http://dx.doi.org/10.1016/j.ijpharm.2013.05.017] [PMID: 23694806] 
[264] 
Guada, M.; Beloqui, A.; Alhouayek, M.; Muccioli, G.G.; Dios-Viéitez, Mdel.C.; Préat, V.; Blanco-Prieto, M.J. Cyclosporine A-loaded lipid nanoparticles in inflammatory bowel disease. Int. J. Pharm.,  2016, 503(1-2), 196-198.
[http://dx.doi.org/10.1016/j.ijpharm.2016.03.012] [PMID: 26972380] 
[265] 
Naeem, M.; Choi, M.; Cao, J.; Lee, Y.; Ikram, M.; Yoon, S.; Lee, J.; Moon, H.R.; Kim, M.S.; Jung, Y.; Yoo, J.W. Colon-targeted delivery of budesonide using dual pH- and time-dependent polymeric nanoparticles for colitis therapy. Drug Des. Devel. Ther.,  2015, 9, 3789-3799.
[PMID: 26229440] 
[266] 
Xu, Q.; Zhang, N.; Qin, W.; Liu, J.; Jia, Z.; Liu, H. Preparation, in vitro and in vivo evaluation of budesonide loaded core/shell nanofibers as oral colonic drug delivery system. J. Nanosci. Nanotechnol.,  2013, 13(1), 149-156.
[http://dx.doi.org/10.1166/jnn.2013.6920] [PMID: 23646710] 
[267] 
Yang, Y-Y.; Liu, Z.P.; Yu, D-G.; Wang, K.; Liu, P.; Chen, X. Colon-specific pulsatile drug release provided by electrospun shellac nanocoating on hydrophilic amorphous composites. Int. J. Nanomedicine,  2018, 13, 2395-2404.
[http://dx.doi.org/10.2147/IJN.S154849] [PMID: 29713169] 
[268] 
Yazeji, T.; Moulari, B.; Beduneau, A.; Stein, V.; Dietrich, D.; Pellequer, Y.; Lamprecht, A. Nanoparticle-based delivery enhances anti-inflammatory effect of low molecular weight heparin in experimental ulcerative colitis. Drug Deliv.,  2017, 24(1), 811-817.
[http://dx.doi.org/10.1080/10717544.2017.1324530] [PMID: 28509629] 
[269] 
Hu, D.; Liu, L.; Chen, W.; Li, S.; Zhao, Y. A novel preparation method for 5-aminosalicylic acid loaded Eudragit S100 nanoparticles. Int. J. Mol. Sci.,  2012, 13(5), 6454-6468.
[http://dx.doi.org/10.3390/ijms13056454] [PMID: 22754377] 
[270] 
Varshosaz, J.; Jaffarian Dehkordi, A.; Golafshan, S. Colon-specific delivery of mesalazine chitosan microspheres. J. Microencapsul.,  2006, 23(3), 329-339.
[http://dx.doi.org/10.1080/02652040600612405] [PMID: 16801244] 
[271] 
Xu, M.; Sun, M.; Qiao, H.; Ping, Q.; Elamin, E.S. Preparation and evaluation of colon adhesive pellets of 5-aminosalicylic acid. Int. J. Pharm.,  2014, 468(1-2), 165-171.
[http://dx.doi.org/10.1016/j.ijpharm.2014.04.040] [PMID: 24746693] 
[272] 
Mladenovska, K.; Raicki, R.S.; Janevik, E.I.; Ristoski, T.; Pavlova, M.J.; Kavrakovski, Z.; Dodov, M.G.; Goracinova, K. Colon-specific delivery of 5-aminosalicylic acid from chitosan-Ca-alginate microparticles. Int. J. Pharm.,  2007, 342(1-2), 124-136.
[http://dx.doi.org/10.1016/j.ijpharm.2007.05.028] [PMID: 17590293] 
[273] 
Ahmed, T.A.; Aljaeid, B.M. Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery. Drug Des. Devel. Ther.,  2016, 10, 483-507.
[http://dx.doi.org/10.2147/DDDT.S99651] [PMID: 26869768] 
[274] 
Bautzová, T.; Rabišková, M.; Béduneau, A.; Pellequer, Y.; Lamprecht, A. Bioadhesive pellets increase local 5-aminosalicylic acid concentration in experimental colitis. Eur. J. Pharm. Biopharm.,  2012, 81(2), 379-385.
[http://dx.doi.org/10.1016/j.ejpb.2012.02.011] [PMID: 22386911] 
[275] 
Niebel, W.; Walkenbach, K.; Béduneau, A.; Pellequer, Y.; Lamprecht, A. Nanoparticle-based clodronate delivery mitigates murine experimental colitis. J. Control. Release,  2012, 160(3), 659-665.
[http://dx.doi.org/10.1016/j.jconrel.2012.03.004] [PMID: 22445727] 
[276] 
Zhang, M.; Viennois, E.; Prasad, M.; Zhang, Y.; Wang, L.; Zhang, Z.; Han, M.K.; Xiao, B.; Xu, C.; Srinivasan, S.; Merlin, D. Edible ginger-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer. Biomaterials,  2016, 101, 321-340.
[http://dx.doi.org/10.1016/j.biomaterials.2016.06.018] [PMID: 27318094] 
[277] 
Yang, C.; Zhang, M.; Merlin, D. Advances in plant-derived edible nanoparticle-based lipid nano-drug delivery systems as therapeutic nanomedicines. J. Mater. Chem. B Mater. Biol. Med.,  2018, 6(9), 1312-1321.
[http://dx.doi.org/10.1039/C7TB03207B] [PMID: 30034807] 
[278] 
Moulari, B.; Béduneau, A.; Pellequer, Y.; Lamprecht, A. Lectin-decorated nanoparticles enhance binding to the inflamed tissue in experimental colitis. J. Control. Release,  2014, 188, 9-17.
[http://dx.doi.org/10.1016/j.jconrel.2014.05.046] [PMID: 24910194] 
[279] 
Coco, R.; Plapied, L.; Pourcelle, V.; Jérôme, C.; Brayden, D.J.; Schneider, Y.J.; Préat, V. Drug delivery to inflamed colon by nanoparticles: comparison of different strategies. Int. J. Pharm.,  2013, 440(1), 3-12.
[http://dx.doi.org/10.1016/j.ijpharm.2012.07.017] [PMID: 22820482] 
[280] 
Mahajan, N.M.; Sakarkar, D.D.M.; Manmode, A.S. Preparation and characterization of meselamine loaded plga nanoparticles. Int. J. Pharm. Pharm. Sci.,  2004, 3(4), 208-214.
[281] 
Ali, H.; Weigmann, B.; Neurath, M.F.; Collnot, E.M.; Windbergs, M.; Lehr, C-M. Budesonide loaded nanoparticles with pH-sensitive coating for improved mucosal targeting in mouse models of inflammatory bowel diseases. J. Control. Release,  2014, 183, 167-177.
[http://dx.doi.org/10.1016/j.jconrel.2014.03.039] [PMID: 24685705] 
[282] 
Anwer, M.K.; Al-Shdefat, R.; Ezzeldin, E.; Alshahrani, S.M.; Alshetaili, A.S.; Iqbal, M. Preparation, evaluation and bioavailability studies of eudragit coated plga nanoparticles for sustained release of eluxadoline for the treatment of irritable bowel syndrome. Front. Pharmacol.,  2017, 8(844), 844.
[http://dx.doi.org/10.3389/fphar.2017.00844] [PMID: 29209215] 
[283] 
Xiao, B.; Yang, Y.; Viennois, E.; Zhang, Y.; Ayyadurai, S.; Baker, M.; Laroui, H.; Merlin, D. Glycoprotein CD98 as a receptor for colitis-targeted delivery of nanoparticle. J. Mater. Chem. B Mater. Biol. Med.,  2014, 2(11), 1499-1508.
[http://dx.doi.org/10.1039/c3tb21564d] [PMID: 24729869] 
[284] 
Wachsmann, P.; Moulari, B.; Béduneau, A.; Pellequer, Y.; Lamprecht, A. Surfactant-dependence of nanoparticle treatment in murine experimental colitis. J. Control. Release,  2013, 172(1), 62-68.
[http://dx.doi.org/10.1016/j.jconrel.2013.07.031] [PMID: 23933520] 
[285] 
Varshosaz, J.; Minaiyan, M.; Khaleghi, N. Eudragit nanoparticles loaded with silybin: a detailed study of preparation, freeze-drying condition and in vitro/in vivo evaluation. J. Microencapsul.,  2015, 32(3), 211-223.
[http://dx.doi.org/10.3109/02652048.2014.995728] [PMID: 25561026] 
[286] 
Castangia, I.; Nácher, A.; Caddeo, C.; Merino, V.; Díez-Sales, O.; Catalán-Latorre, A.; Fernàndez-Busquets, X.; Fadda, A.M.; Manconi, M. Therapeutic efficacy of quercetin enzyme-responsive nanovesicles for the treatment of experimental colitis in rats. Acta Biomater.,  2015, 13, 216-227.
[http://dx.doi.org/10.1016/j.actbio.2014.11.017] [PMID: 25463498] 
[287] 
Gulbake, A.; Jain, S.K. Colon specific delivery of mesalazine using biocompatible polymeric nanoparticles. Int. J. Pharmacol. Pharm. Technol.,  2018, 2(1), 17-24.
[288] 
Leoni, G.; Neumann, P.A.; Kamaly, N.; Quiros, M.; Nishio, H.; Jones, H.R.; Sumagin, R.; Hilgarth, R.S.; Alam, A.; Fredman, G.; Argyris, I.; Rijcken, E.; Kusters, D.; Reutelingsperger, C.; Perretti, M.; Parkos, C.A.; Farokhzad, O.C.; Neish, A.S.; Nusrat, A. Annexin A1-containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair. J. Clin. Invest.,  2015, 125(3), 1215-1227.
[http://dx.doi.org/10.1172/JCI76693] [PMID: 25664854] 
[289] 
Beloqui, A.; Coco, R.; Memvanga, P.B.; Ucakar, B.; des Rieux, A.; Préat, V. pH-sensitive nanoparticles for colonic delivery of curcumin in inflammatory bowel disease. Int. J. Pharm.,  2014, 473(1-2), 203-212.
[http://dx.doi.org/10.1016/j.ijpharm.2014.07.009] [PMID: 25014369] 
[290] 
Chen, Q.; Si, X.; Ma, L.; Ma, P.; Hou, M.; Bai, S.; Wu, X.; Wan, Y.; Xiao, B.; Merlin, D. Oral delivery of curcumin via porous polymeric nanoparticles for effective ulcerative colitis therapy. J. Mater. Chem. B Mater. Biol. Med.,  2017, 5(29), 5881-5891.
[http://dx.doi.org/10.1039/C7TB00328E] [PMID: 29081976] 
[291] 
Zhu, C.; Zhang, S.; Song, C.; Zhang, Y.; Ling, Q.; Hoffmann, P.R.; Li, J.; Chen, T. Zheng,w.;Huang, Z. Selenium nanoparticles decorated with Ulva lactuca polysaccharide potentially attenuate colitis by inhibiting NF-κB mediated hyper inflammation. J. Nanobiotechnology,  2017, 15(20), 1-15.
[292] 
Zeeshan, M.; Ali, H.; Khan, S.; Mukhtar, M.; Khan, M.I.; Arshad, M. Glycyrrhizic acid-loaded pH-sensitive poly-(lactic-co-glycolic acid) nanoparticles for the amelioration of inflammatory bowel disease. Nanomedicine (Lond.),  2019, 14(15), 1945-1969.
[http://dx.doi.org/10.2217/nnm-2018-0415] [PMID: 31355705] 
[293] 
Gou, S.; Chen, Q.; Liu, Y.; Zeng, L.; Song, H.; Xu, Z.; Kang, Y. Li,c.; Xiao, B. Green fabrication of ovalbumin nanoparticles as natural polyphenol carriers for ulcerative colitis therapy. ACS Sustain. Chem.& Eng.,  2018, 6(10), 12658-12667.
[http://dx.doi.org/10.1021/acssuschemeng.8b01613] 
[294] 
Zhang, M.; Xu, C.; Liu, D.; Han, M.K.; Wang, L.; Merlin, D. Oral delivery of nanoparticles loaded with ginger active compound, 6-shogaol, attenuates ulcerative colitis and promotes wound healing in a murine model of ulcerative colitis. J. Crohn’s Colitis,  2018, 12(2), 217-229.
[http://dx.doi.org/10.1093/ecco-jcc/jjx115] [PMID: 28961808] 
[295] 
Van Toi, V.; Le, T.Q.; Ngo, H.T.; Nguyen, T-H. 7th International
Conference on the Development of Biomedical Engineering in
Vietnam (BME7). Proceedings of BME; International Conference
on the Development of Biomedical Engineering in Vietnam;
Aachen: Germany,  2007. 
[http://dx.doi.org/10.1007/978-981-13-5859-3] 
[296] 
Ball, R.L.; Bajaj, P.; Whitehead, K.A. Oral delivery of siRNA lipid nanoparticles: Fate in the GI tract. Sci. Rep.,  2018, 8(1), 2178.
[http://dx.doi.org/10.1038/s41598-018-20632-6] [PMID: 29391566] 
[297] 
Ruiz, P.A.; Morón, B.; Becker, H.M.; Lang, S.; Atrott, K.; Spalinger, M.R.; Scharl, M.; Wojtal, K.A.; Fischbeck-Terhalle, A.; Frey-Wagner, I.; Hausmann, M.; Kraemer, T.; Rogler, G. Titanium dioxide nanoparticles exacerbate DSS-induced colitis: role of the NLRP3 inflammasome. Gut,  2017, 66(7), 1216-1224.
[http://dx.doi.org/10.1136/gutjnl-2015-310297] [PMID: 26848183] 
Rights & Permissions Print Cite
Article Metrics
35
5
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1568026620666200320113322	Print ISSN 1568-0266
Publisher Name Bentham Science Publisher	Online ISSN 1873-4294
Current Topics in Medicinal Chemistry

Application of Polymeric Nano-Materials in Management of Inflammatory Bowel Disease

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Abstract
