• SOUMYADIP GHOSH Department of Pharmaceutics, Calcutta Institute of Pharmaceutical Technology and AHS, Uluberia, Howrah, West Bengal 711316 https://orcid.org/0000-0003-0177-1328
  • DEBGOPAL GANGULY School of Pharmacy, Seacom Skills University, Bolpur, Birbhum, West Bengal 731236
  • SUBHABROTA MAJUMDER Department of Pharmaceutics, Calcutta Institute of Pharmaceutical Technology and AHS, Uluberia, Howrah, West Bengal 711316




Ozanimod, Inflammatory bowel disease, Sphingosine-1-phosphate receptors, Colon targeted drug delivery systems, Multiple sclerosis, Recent advancement


Current drug treatments are focused on pharmacological and chemotherapeutical treatment such as controlling the acute and chronic aggravation of diseases, maintaining remission, treating specific complications, and reducing the toxic effects. Several drugs are inappropriate for long-term therapy due to high toxicity levels and the inability to maintain remission of the therapy. An inflammatory bowel disease is a group of idiopathic, chronic, and pathological conditions which pursue protracted relapsing and remitting course cause prolonged inflammation in the gastrointestinal tract, including diarrhea, abdominal pain, bleeding, anemia, and weight loss due to dysregulated immune response. Several drugs have been come to the market to treat inflammatory bowel disease, but they are not potential to the patient due to their higher toxicity rate and low therapeutic activity. Ozanimod is an anti-inflammatory and neuroprotective oral selective modulator of sphingosine-1-phosphate selectively targeting inflammatory bowel disease like ulcerative colitis and Crohn’s disease and is also involved in the treatment of multiple sclerosis. There is no serious adverse effect, as well as adverse events such as cardiac events, serious infections, or macular edema, was found in the treatment of inflammatory bowel disease. The conventional drug delivery of ozanimod has severe adverse effects, which can be reduced by nanocarrier and stability and bioavailability can be enhanced. This review discusses the Pharmacological and therapeutical insight of Ozanimod for targeting inflammatory bowel diseases like Ulcerative colitis and Crohn’s disease as well as Multiple Sclerosis and the importance of nanocarriers for Ozanimod to target the colon region and recent advancement technology introduced to Ozanimod.


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Burisch J, Pedersen N, Cukovic Cavka S, Brinar M, Kaimakliotis I, Duricova D, Shonova O, Vind I, Avnstrøm S, Thorsgaard N, Andersen V, Krabbe S, Dahlerup JF, Salupere R, Nielsen KR, Olsen J, Manninen P, Collin P, Tsianos EV, Katsanos KH, Ladefoged K, Lakatos L, Björnsson E, Ragnarsson G, Bailey Y, Odes S, Schwartz D, Martinato M, Lupinacci G, Milla M, De Padova A, D’Inca R, Beltrami M, Kupcinskas L, Kiudelis G, Turcan S, Tighineanu O, Mihu I, Magro F, Barros LF, Goldis A, Lazar D, Belousova E, Nikulina I, Hernandez V, Martinez-Ares D, Almer S, Zhulina Y, Halfvarson J, Arebi N, Sebastian S, Lakatos PL, Langholz E, Munkholm P, EpiCom-group. East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort. Gut. 2014;63(4):588-97. doi: 10.1136/gutjnl-2013-304636, PMID 23604131.

Thia KT, Loftus EV, Sandborn WJ, Yang SK. An update on the epidemiology of inflammatory bowel disease in Asia. Am J Gastroenterol. 2008;103(12):3167-82. doi: 10.1111/j.1572-0241.2008.02158.x. PMID 19086963.

Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, Burisch J, Gecse KB, Hart AL, Hindryckx P, Langner C, Limdi JK, Pellino G, Zagórowicz E, Raine T, Harbord M, Rieder F, European Crohn’s and Colitis Organisation [ECCO]. Third European evidence-based consensus on diagnosis and management of ulcerative colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders. J Crohns Colitis. 2017;11(6):649-70. doi: 10.1093/ecco-jcc/jjx008, PMID 28158501.

Malinowski KP, Kawalec P. Health utility of patients with Crohn’s disease and ulcerative colitis: a systematic review and meta-analysis. Expert Rev Pharmacoecon Outcomes Res. 2016;16(4):441-53. doi: 10.1080/14737167.2016.1190644, PMID 27187028.

Persson PG, Ahlbom A, Hellers G. Crohn’s disease and ulcerative colitis. A review of dietary studies with emphasis on methodologic aspects. Scand J Gastroenterol. 1987;22(4):385-9. doi: 10.3109/00365528708991479, PMID 3299676.

Moskovitz DN, Bodian C, Chapman ML, Marion JF, Rubin PH, Scherl E, Present DH. The effect on the fetus of medications used to treat pregnant inflammatory bowel-disease patients. Am J Gastroenterol. 2004;99(4):656-61. doi: 10.1111/j.1572-0241.2004.04140.x. PMID 15089898.

Holleran G, Lopetuso L, Petito V, Graziani C, Ianiro G, McNamara D, Gasbarrini A, Scaldaferri F. The innate and adaptive immune system as targets for biologic therapies in inflammatory bowel disease. Int J Mol Sci. 2017;18(10):2020. doi: 10.3390/ijms18102020, PMID 28934123.

Hegner J, Patel J, Fong S, Jeffs S. The role of a specialist pharmacist in the management of adalimumab in patients with inflammatory bowel disease. Int J Pharm Pharm Sci. 2021;13(11):30-3. doi: 10.22159/ijpps.2021v13i11.42451.

Im DS, Heise CE, Ancellin N, O’Dowd BF, Shei GJ, Heavens RP, Rigby MR, Hla T, Mandala S, McAllister G, George SR, Lynch KR. Characterization of a novel sphingosine 1-phosphate receptor, Edg-8. J Biol Chem. 2000;275(19):14281-6. doi: 10.1074/ jbc.275.19.14281.

Mandala S, Hajdu R, Bergstrom J, Quackenbush E, Xie J, Milligan J, Thornton R, Shei GJ, Card D, Keohane C, Rosenbach M, Hale J, Lynch CL, Rupprecht K, Parsons W, Rosen H. Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science. 2002 Apr 12;296(5566):346-9. doi: 10.1126/science.1070238, PMID 11923495.

Hobson JP, Rosenfeldt HM, Barak LS, Olivera A, Poulton S, Caron MG, Milstien S, Spiegel S. Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility. Science. 2001;291(5509):1800-3. doi: 10.1126/ science.1057559, PMID 11230698.

Perez Jeldres T, Alvarez Lobos M, Rivera Nieves J. Targeting sphingosine-1-phosphate signaling in immune-mediated diseases: beyond multiple sclerosis. Drugs. 2021;81(9):985-1002. doi: 10.1007/s40265-021-01528-8, PMID 33983615.

Wang J, Goren I, Yang B, Lin S, Li J, Elias M, Fiocchi C, Rieder F. Review article: the sphingosine 1 phosphate/sphingosine 1 phosphate receptor axis - a unique therapeutic target in inflammatory bowel disease. Aliment Pharmacol Ther. 2022;55(3):277-91. doi: 10.1111/apt.16741. PMID 34932238.

Lasa JS, Olivera PA, Bonovas S, Danese S, Peyrin Biroulet L. Safety of S1P modulators in patients with immune-mediated diseases: a systematic review and meta-analysis. Drug Saf. 2021;44(6):645-60. doi: 10.1007/s40264-021-01057-z, PMID 33666900.

Musella A, Gentile A, Guadalupi L, Rizzo FR, De Vito F, Fresegna D, Bruno A, Dolcetti E, Vanni V, Vitiello L, Bullitta S, Sanna K, Caioli S, Balletta S, Nencini M, Buttari F, Stampanoni Bassi M, Centonze D, Mandolesi G. Central modulation of selective sphingosine-1-phosphate receptor 1 ameliorates experimental multiple sclerosis. Cells. 2020;9(5):1290-8. doi: 10.3390/cells9051290, PMID 32455907.

Derfuss T, Mehling M, Papadopoulou A, Bar-Or A, Cohen JA, Kappos L. Advances in oral immunomodulating therapies in relapsing multiple sclerosis. Lancet Neurol. 2020;19(4):336-47. doi: 10.1016/S1474-4422(19)30391-6, PMID 32059809.

Lamb YN. Ozanimod: first approval. Drugs. 2020 Jun;80(8):841-8. doi: 10.1007/s40265-020-01319-7, PMID 32385738.

Rasche L, Paul F. Ozanimod for the treatment of relapsing remitting multiple sclerosis. Expert Opin Pharmacother. 2018;19(18):2073-86. doi: 10.1080/14656566.2018.1540592, PMID 30407868.

Al-Zaqri N, Pooventhiran T, Rao DJ, Alsalme A, Warad I, Thomas R. Structure, conformational dynamics, quantum mechanical studies and potential biological activity analysis of multiple sclerosis medicine ozanimod. J Mol Struct. 2021;1227. doi: 10.1016/j.molstruc.2020.129685, PMID 129685.

Alsalme A, Pooventhiran T, Al-Zaqri N, Rao DJ, Thomas R. Structural, physico-chemical landscapes, ground state and excited state properties in different solvent atmosphere of Avapritinib and its ultrasensitive detection using SERS/GERS on self-assembly formation with graphene quantum dots. J Mol Liq. 2021;322. doi: 10.1016/j.molliq.2020.114555, PMID 114555.

Surapaneni S, Yerramilli U, Bai A, Dalvie D, Brooks J, Wang X, Selkirk JV, Yan YG, Zhang P, Hargreaves R, Kumar G, Palmisano M, Tran JQ. Absorption, metabolism, and excretion, in vitro pharmacology, and clinical pharmacokinetics of Ozanimod, a novel sphingosine 1-phosphate receptor modulator. Drug Metab Dispos. 2021;49(5):405-19. doi: 10.1124/dmd.120.000220, PMID 33674268.

Selkirk JV, Dines KC, Yan YG, Ching N, Dalvie D, Biswas S, Bortolato A, Schkeryantz JM, Lopez C, Ruiz I, Hargreaves R. Deconstructing the pharmacological contribution of Sphingosine-1 phosphate receptors to mouse models of multiple sclerosis using the species selectivity of Ozanimod, a dual modulator of human sphingosine 1-phosphate receptor subtypes 1 and 5. J Pharmacol Exp Ther. 2021;379(3):386-99. doi: 10.1124/jpet.121.000741, PMID 34535564.

Hatoum D, Haddadi N, Lin Y, Nassif NT, McGowan EM. Mammalian sphingosine kinase (SphK) isoenzymes and isoform expression: challenges for SphK as an oncotarget. Oncotarget. 2017;8(22):36898-929. doi: 10.18632/ oncotarget.16370, PMID 28415564.

Chun J, Giovannoni G, Hunter SF. Sphingosine 1-phosphate receptor modulator therapy for multiple sclerosis: differential downstream receptor signalling and clinical profile effects. Drugs. 2021;81(2):207-31. doi: 10.1007/s40265-020-01431-8, PMID 33289881.

Tran JQ, Hartung JP, Peach RJ, Boehm MF, Rosen H, Smith H, Brooks JL, Timony GA, Olson AD, Gujrathi S, Frohna PA. Results from the first‐in-human study with ozanimod, a novel, selective sphingosine‐1‐phosphate receptor modulator. J Clin Pharmacol. 2017;57(8):988-96. doi: 10.1002/jcph.887, PMID 28398597.

Scott FL, Clemons B, Brooks J, Brahmachary E, Powell R, Dedman H, Desale HG, Timony GA, Martinborough E, Rosen H, Roberts E, Boehm MF, Peach RJ. Ozanimod (RPC1063) is a potent sphingosine‐1‐phosphate receptor‐1 (S1P1) and receptor‐5 (S1P5) agonist with autoimmune disease‐modifying activity. Br J Pharmacol. 2016;173(11):1778-92. doi: 10.1111/bph.13476, PMID 26990079.

Harris S, Tran JQ, Southworth H, Spencer CM, Cree BAC, Zamvil SS. Effect of the sphingosine-1-phosphate receptor modulator ozanimod on leukocyte subtypes in relapsing MS. Neurol Neuroimmunol Neuroinflamm. 2020;7(5):1-9. doi: 10.1212/NXI.0000000000000839, PMID 32737072.

Peyrin Biroulet L, Christopher R, Behan D, Lassen C. Modulation of sphingosine-1-phosphate in inflammatory bowel disease. Autoimmun Rev. 2017;16(5):495-503. doi: 10.1016/j.autrev.2017.03.007, PMID 28279838.

Aminu N, Bello I, Umar NM, Tanko N, Aminu A, Audu MM. The influence of nanoparticulate drug delivery systems in drug therapy. J Drug Deliv Sci Technol. 2020;60. doi: 10.1016/j.jddst.2020.101961.

Keservani RK, Sharma AK, editors. Nanoparticulate drug delivery systems. CRC Press; 2019.

Feagan BG, Sandborn WJ, Danese S, Wolf DC, Liu WJ, Hua SY, Minton N, Olson A, D’Haens G. Ozanimod induction therapy for patients with moderate to severe Crohn’s disease: a single-arm, phase 2, prospective observer-blinded endpoint study. Lancet Gastroenterol Hepatol. 2020;5(9):819-28. doi: 10.1016/S2468-1253(20)30188-6, PMID 32553149.

Comi G, Kappos L, Selmaj KW, Bar-Or A, Arnold DL, Steinman L, Hartung HP, Montalban X, Kubala Havrdova EK, Cree BAC, Sheffield JK, Minton N, Raghupathi K, Ding N, Cohen JA, SUNBEAM Study Investigators. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12 mo, phase 3 trial. Lancet Neurol. 2019;18(11):1009-20. doi: 10.1016/S1474-4422(19)30239-X, PMID 31492651.

Sandborn WJ, Feagan BG, Hanauer S, Vermeire S, Ghosh S, Liu WJ, Petersen A, Charles L, Huang V, Usiskin K, Wolf DC, D’Haens G. Long-term efficacy and safety of ozanimod in moderately to severely active ulcerative colitis: results from the open-label extension of the randomized, phase 2 touchstone study. J Crohns Colitis. 2021;15(7):1120-9. doi: 10.1093/ecco-jcc/jjab012, PMID 33438008.

Broesder A, Woerdenbag HJ, Prins GH, Nguyen DN, Frijlink HW, Hinrichs WLJ. PH-dependent ileocolonic drug delivery, part I: In vitro and clinical evaluation of novel systems. Drug Discov Today. 2020;25(8):1362-73. doi: 10.1016/j.drudis. 2020.06.011, PMID 32554060.

Shibaev AV, Muravlev DA, Muravleva AK, Matveev VV, Chalykh AE, Philippova OE. PH-dependent gelation of a stiff anionic polysaccharide in the presence of metal ions. Polymers. 2020;12(4):868-78. doi: 10.3390/polym12040868, PMID 32290178.

Blanco PM, Madurga S, Mas F, Garces JL. Coupling of charge regulation and conformational equilibria in weak linear polyelectrolytes: treatment of long-range interactions via effective short-ranged and pH-dependent interaction parameters. Polymers. 2018;10(8):811-21. doi: 10.3390/polym10080811, PMID 30960736.

Lazzari F, Manfredi A, Alongi J, Marinotto D, Ferruti P, Ranucci E. d-, l- and d, l-tryptophan-based polyamidoamino acids: pH-dependent structuring and fluorescent properties. Polymers. 2019;11(3):543. doi: 10.3390/polym11030543, PMID 30960527.

Monschke M, Wagner KG. Amorphous solid dispersions of weak bases with pH-dependent soluble polymers to overcome limited bioavailability due to gastric pH variability- an in vitro approach. Int J Pharm. 2019;564:162-70. doi: 10.1016/j.ijpharm.2019.04.034, PMID 30991134.

Khan AM, Hanif M, Bukhari NI, Shamim R, Rasool F, Rasul S, Shafique S. Artificial neural network (ANN) approach to predict an optimized pH-dependent mesalamine matrix tablet. Drug Des Devel Ther. 2020;14(2):2435-48. doi: 10.2147/DDDT.S244016, PMID 32606610.

Wang Z, Deng X, Ding J, Zhou W, Zheng X, Tang G. Mechanisms of drug release in pH-sensitive micelles for tumour targeted drug delivery system: a review. Int J Pharm. 2018;535(1-2):253-60. doi: 10.1016/j.ijpharm.2017.11.003. PMID 29113804.

Sardo HS, Saremnejad F, Bagheri S, Akhgari A, Garekani HA, Sadeghi F. A review on 5-aminosalicylic acid colon-targeted oral drug delivery systems. Int J Pharm. 2019;558(1):367-79.

Zhang B, Yan Y, Shen Q, Ma D, Huang L, Cai X, Tan S. A colon targeted drug delivery system based on alginate modificated graphene oxide for colorectal liver metastasis. Mater Sci Eng C. 2017;79:185-90. doi: 10.1016/j.msec.2017.05.054.

Chourasia MK, Jain SK. Polysaccharides for colon targeted drug delivery. Drug Deliv. 2004;11(2):129-48. doi: 10.1080/10717540490280778, PMID 15200012.

Kumar P, Mishra B. Colon targeted drug delivery systems-an overview. Curr Drug Deliv. 2008;5(3):186-98. doi: 10.2174/156720108784911712, PMID 18673262.

Rozi MF, Mohmad Sabere AS. Review on conventional and novel topical ocular drug delivery system. JoP. 2021;1(1):19-26. doi: 10.31436/jop.v1i1.32.

Yu W, Liu R, Zhou Y, Gao H. Size tunable strategies for a tumor-targeted drug delivery system. ACS Cent Sci. 2020;6(2):100-16. doi: 10.1021/acscentsci.9b01139, PMID 32123729.

Hu M, Ge X, Chen X, Mao W, Qian X, Yuan WE. Micro/nanorobot: A promising targeted drug delivery system. Pharmaceutics. 2020;12(7):665-75. doi: 10.3390/pharmaceutics12070665, PMID 32679772.

Huang G, Huang H. Hyaluronic acid-based biopharmaceutical delivery and tumor-targeted drug delivery system. J Control Release. 2018;278(1):122-6. doi: 10.1016/ j.jconrel.2018.04.015, PMID 29649528.

Wang Z, Duan Y, Duan Y. Application of polydopamine in tumor targeted drug delivery system and its drug release behavior. J Control Release. 2018;290(1):56-74. doi: 10.1016/j.jconrel.2018.10.009, PMID 30312718.

Hoang HT, Jo SH, Phan QT, Park H, Park SH, Oh CW, Lim KT. Dual pH-/thermo-responsive chitosan-based hydrogels prepared using “click” chemistry for colon-targeted drug delivery applications. Carbohydr Polym. 2021;260:117812. doi: 10.1016/j.carbpol.2021.117812.

Zhang S, Langer R, Traverso G. Nanoparticulate drug delivery systems targeting inflammation for treatment of inflammatory bowel disease. Nano Today. 2017;16:82-96. doi: 10.1016/j.nantod.2017.08.006, PMID 31186671.

Zhang Y, Cui Z, Mei H, Xu J, Zhou T, Cheng F, Wang K. Angelica sinensis polysaccharide nanoparticles as a targeted drug delivery system for enhanced therapy of liver cancer. Carbohydr Polym. 2019;219(1):143-54. doi: 10.1016/j.carbpol.2019.04.041, PMID 31151511.

Banerjee S. Nanoparticle-mediated therapeutic approach for ulcerative colitis treatment. Diagnostic and Treatment Methods for Ulcerative Colitis and Colitis Associated Cancer 2021:96-117.

Ram D, Pankhaniya H. Formulation, evaluation and optimization of sustained-release drug delivery system of cisapride tablet. Int J Pharm Pharm Sci. 2021;13(9):56-62. doi: 10.22159/Ijpps.2021v13i9.41799.

Courthion H, Mugnier T, Rousseaux C, Möller M, Gurny R, Gabriel D. Self-assembling polymeric nanocarriers to target inflammatory lesions in ulcerative colitis. J Control Release. 2018;275:32-9. doi: 10.1016/j.jconrel.2017.07.044, PMID 28774843.

Leppert W, Malec Milewska M, Zajaczkowska R, Wordliczek J. Transdermal and topical drug administration in the treatment of pain. Molecules. 2018;23(3):681-91. doi: 10.3390/molecules23030681, PMID 29562618.

Guo YG, Singh AP. Emerging strategies for enhancing buccal and sublingual administration of nutraceuticals and pharmaceuticals. J Drug Deliv Sci Technol. 2019;52(1):440-51.

Gulati M, Singh SK, Corrie L, Kaur IP, Chandwani L. Delivery routes for faecal microbiota transplants: Available, anticipated and aspired. Pharmacol Res. 2020;159(1):104954. doi: 10.1016/j.phrs.2020.104954, PMID 32492490.

Korani S, Bahrami S, Korani M, Banach M, Johnston TP, Sahebkar A. Parenteral systems for statin delivery: a review. Lipids Health Dis. 2019;18(1):193. doi: 10.1186/s12944-019-1139-8, PMID 31690335.

Kumari P, Ghosh B, Biswas S. Nanocarriers for cancer-targeted drug delivery. J Drug Target. 2016;24(3):179-91. doi: 10.3109/1061186X.2015.1051049, PMID 26061298.

Deepika B, Sameen S, Nazneen N, Madhavi A, Raju KN, Rao KN, Dutt KR. Matrix drug delivery system: a review. Eur J Pharm Med Res. 2018;5(1):150-4.

Priyanka P, Sri Rekha M, Devi AS. Review on formulation and evaluation of solid lipid nanoparticles for vaginal application. International Journal of Pharmacy and Pharmaceutical Sciences. 2022;14(1):1-8. doi: 10.22159/Ijpps.2022v14i1.42595.

Chaudhary RG, Bhusari GS, Tiple AD, Rai AR, Somkuvar SR, Potbhare AK, Lambat TL, Ingle PP, Abdala AA. Metal/metal oxide nanoparticles: toxicity, applications, and prospects. Current Pharmaceutical Design. 2019;12(4):25-32.



How to Cite

GHOSH, S., D. GANGULY, and S. MAJUMDER. “A REVIEW ON PHARMACOLOGICAL AND THERAPEUTIC INSIGHT OF OZANIMOD FOR COLON DISEASE IN NANO-STRUCTURE”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 14, no. 4, Apr. 2022, pp. 13-19, doi:10.22159/ijpps.2022v14i4.44150.



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