Vol 26, No 5 (2021)
Research paper
Published online: 2021-08-17

open access

Page views 6798
Article views/downloads 713
Get Citation

Connect on Social Media

Connect on Social Media

Therapeutic efficacy of rifaximin loaded tamarind gum polysaccharide nanoparticles in TNBS induced IBD model Wistar rats

Maria John Newton Amaldoss12, Imtiyaz Ahmed3, Jatinder Kumar4, Archana Sharma3
Rep Pract Oncol Radiother 2021;26(5):712-729.

Abstract

Background: Rifaximin is a non-systemic antibiotic used in the treatment of inflammatory bowel disease (IBD). Antibiotics are demonstrating a significant role in the treatment of IBD by altering the dysbiotic colonic microbiota and decreases the immunogenic and inflammatory response in the patient population. Mucoadhesive colon targeted nanoparticles provide the site-specific delivery and extended stay in the colon. Since the bacteria occupy the lumen, spread over the surface of epithelial cells, and adhere to the mucosa, delivering the rifaximin as a nanoparticles with the mucoadhesive polymer enhances the therapeutic efficacy in IBD.

The objective was to fabricate and characterize the rifaximin loaded tamarind gun nanoparticles and  study the therapeutic efficacy in the TNBS-induced IBD model rats.

Materials and methods: The experimentation includes fabrication and characterization of drug excipient compatibility by FTIR. The fabricated nanoparticles were characterized for the hydrodynamic size and zeta potential by photon correlation spectroscopy and also analyzed by TEM. Selected best formulation was subjected to the therapeutic efficacy study in TNBS-induced IBD rats, and the macroscopic, microscopic and biochemical parameters were reported.

Results: The study demonstrated that the formulation TGN1 is best formulation in terms of nanoparticle characterization and hydrodynamic size which showed the hydrodynamic size of 171.4 nm and the zeta potential of –26.44 mV and other parameters such as TEM and drug release studies were also reported. The therapeutic efficacy study revealed that TGN1 is efficiently reduced the IBD inflammatory conditions as compared to the TNBS control group and reference drug mesalamine group.

Article available in PDF format

View PDF Download PDF file

References

  1. Huang Y, Chen Z. Inflammatory bowel disease related innate immunity and adaptive immunity. Am J Transl Res. 2016; 8(6): 2490–2497.
  2. Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014; 157(1): 121–141.
  3. Matricon J, Barnich N, Ardid D. Immunopathogenesis of inflammatory bowel disease. Self Nonself. 2010; 1(4): 299–309.
  4. Currò D, Pugliese D, Armuzzi A. Frontiers in Drug Research and Development for Inflammatory Bowel Disease. Front Pharmacol. 2017; 8: 400.
  5. Kumar J, Newton AJ. IBD Modern Concepts, Nano Drug Delivery and Patents: An Update. Recent Patents Nanomed. 2015; 5(2): 122–145.
  6. Sartor RB, Sartor RB. Current concepts of the etiology and pathogenesis of ulcerative colitis and Crohn's disease. Gastroenterol Clin North Am. 1995; 24(3): 475–507.
  7. Ott SJ, Musfeldt M, Wenderoth DF, et al. Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease. Gut. 2004; 53(5): 685–693.
  8. Frank DN, St Amand AL, Feldman RA, et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A. 2007; 104(34): 13780–13785.
  9. Sokol H, Pigneur B, Watterlot L, et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci U S A. 2008; 105(43): 16731–16736.
  10. Perencevich M, Burakoff R. Use of antibiotics in the treatment of inflammatory bowel disease. Inflamm Bowel Dis. 2006; 12(7): 651–664.
  11. Maccaferri S, Vitali B, Klinder A, et al. Rifaximin modulates the colonic microbiota of patients with Crohn's disease: an in vitro approach using a continuous culture colonic model system. J Antimicrob Chemother. 2010; 65(12): 2556–2565.
  12. Brown CL, Smith K, Wall DM, et al. Activity of Species-specific Antibiotics Against Crohn's Disease-Associated Adherent-invasive Escherichia coli. Inflamm Bowel Dis. 2015; 21(10): 2372–2382.
  13. Sartor RB. Review article: the potential mechanisms of action of rifaximin in the management of inflammatory bowel diseases. Aliment Pharmacol Ther. 2016; 43 Suppl 1: 27–36.
  14. Wan YC, Li T, Han YD, et al. Effect of pregnane xenobiotic receptor activation on inflammatory bowel disease treated with rifaximin. J Biol Regul Homeost Agents. 2015; 29(2): 401–410.
  15. Kolios G, Manousou P, Bourikas L, et al. Ciprofloxacin inhibits cytokine-induced nitric oxide production in human colonic epithelium. Eur J Clin Invest. 2006; 36(10): 720–729.
  16. Labro MT. Antibiotics as anti-inflammatory agents. Curr Opin Investig Drugs. 2002; 3(1): 61–68.
  17. Huckle AW, Fairclough LC, Todd I. Prophylactic Antibiotic Use in COPD and the Potential Anti-Inflammatory Activities of Antibiotics. Respir Care. 2018; 63(5): 609–619.
  18. Rosette C, Buendia-Laysa F, Patkar S, et al. Anti-inflammatory and immunomodulatory activities of rifamycin SV. Int J Antimicrob Agents. 2013; 42(2): 182–186.
  19. Mostafa T, Badra G, Abdallah M. The efficacy and the immunomodulatory effect of rifaximin in prophylaxis of spontaneous bacterial peritonitis in cirrhotic Egyptian patients. Turk J Gastroenterol. 2015; 26(2): 163–169.
  20. Scarpignato C, Pelosini I. Rifaximin, a poorly absorbed antibiotic: pharmacology and clinical potential. Chemotherapy. 2005; 51 Suppl 1: 36–66.
  21. Ojetti V, Lauritano EC, Barbaro F, et al. Rifaximin pharmacology and clinical implications. Expert Opin Drug Metab Toxicol. 2009; 5(6): 675–682.
  22. Venturini AP. Pharmacokinetics of L/105, a new rifamycin, in rats and dogs, after oral administration. Chemotherapy. 1983; 29(1): 1–3.
  23. Yang J, Lee HR, Low K, et al. Rifaximin versus other antibiotics in the primary treatment and retreatment of bacterial overgrowth in IBS. Dig Dis Sci. 2008; 53(1): 169–174.
  24. Guslandi M, Guslandi M, Guslandi M, et al. Antibiotics for inflammatory bowel disease: do they work? Eur J Gastroenterol Hepatol. 2005; 17(2): 145–147.
  25. Prantera C, Lochs H, Grimaldi M, et al. Retic Study Group (Rifaximin-Eir Treatment in Crohn's Disease). Rifaximin-extended intestinal release induces remission in patients with moderately active Crohn's disease. Gastroenterology. 2012; 142(3): 473–481.e4.
  26. Shayto RH, Abou Mrad R, Sharara AI. Use of rifaximin in gastrointestinal and liver diseases. World J Gastroenterol. 2016; 22(29): 6638–6651.
  27. Ledder O. Antibiotics in inflammatory bowel diseases: do we know what we're doing? Transl Pediatr. 2019; 8(1): 42–55.
  28. Flint HJ, Scott KP, Duncan SH, et al. Microbial degradation of complex carbohydrates in the gut. Gut Microbes. 2012; 3(4): 289–306.
  29. Lovegrove A, Edwards CH, De Noni I, et al. Role of polysaccharides in food, digestion, and health. Crit Rev Food Sci Nutr. 2017; 57(2): 237–253.
  30. Newton AMJ, Indana VL, Kumar J. Chronotherapeutic drug delivery of Tamarind gum, Chitosan and Okra gum controlled release colon targeted directly compressed Propranolol HCl matrix tablets and in-vitro evaluation. Int J Biol Macromol. 2015; 79: 290–299.
  31. Durai R, Rajalakshmi G, Joseph J, et al. Tamarind seed polysaccharide: A promising natural excipient for pharmaceuticals. Int J Green Pharm. 2012; 6(4): 270.
  32. Newton MJ, Prabhakaran L, Kabilan P. Drug Deliveries to Colonic Region. Indian Pharm. 2011; 9: PP–23.
  33. Joseph J, Kanchalochana S, Rajalakshmi G, et al. Tamarind seed polysaccharide: A promising natural excipient for pharmaceuticals. Int J Green Pharm . 2012; 6(4).
  34. Nayak A, Pal D. Functionalization of Tamarind Gum for Drug Delivery. Funct Biopolymers. 2017: 25–56.
  35. Gorbach SL. Microbiology of the Gastrointestinal Tract. In: Baron S. ed. Medical Microbiology. University of Texas Medical Branch at Galveston, Galveston 1996.
  36. Jess T, Simonsen J, Nielsen NM, et al. Enteric Salmonella or Campylobacter infections and the risk of inflammatory bowel disease. Gut. 2011; 60(3): 318.
  37. Mehmood R, Amaldoss MJN. Fabrication and characterisation of lavender oil — plant phospholipid based Sumatriptan succinate hybrid solid lipid nanoparticles. Pharm Biomed Res. 2020; 6(1): 91–104.
  38. Morris G, Beck P, Herridge M, et al. Hapten-Induced Model of Chronic Inflammation and Ulceration in the Rat Colon. Gastroenterology. 1989; 96(2): 795–803.
  39. Cheng J, Shah YM, Ma X, et al. Therapeutic role of rifaximin in inflammatory bowel disease: clinical implication of human pregnane X receptor activation. J Pharmacol Exp Ther. 2010; 335(1): 32–41.
  40. Ohwada K. [Improvement of cardiac puncture in mice]. Jikken Dobutsu. 1986; 35(3): 353–355.
  41. Bell CJ, Gall DG, Wallace JL. Disruption of colonic electrolyte transport in experimental colitis. Am J Physiol. 1995; 268(4 Pt 1): G622–G630.
  42. Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med. 1963; 61: 882–888.
  43. Buege J, Aust S. [30] Microsomal lipid peroxidation. Meth Enzymol. 1978: 302–310.
  44. Miranda K, Espey M, Wink D. A Rapid, Simple Spectrophotometric Method for Simultaneous Detection of Nitrate and Nitrite. Nitric Oxide. 2001; 5(1): 62–71.
  45. Krawisz JE, Sharon P, Stenson WF. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Gastroenterology. 1984; 87(6): 1344–1350.
  46. Fontana M, Mosca L, Rosei MA. Interaction of enkephalins with oxyradicals. Biochem Pharmacol. 2001; 61(10): 1253–1257.
  47. Arab HH, Al-Shorbagy MY, Abdallah DM, et al. Telmisartan attenuates colon inflammation, oxidative perturbations and apoptosis in a rat model of experimental inflammatory bowel disease. PLoS One. 2014; 9(5): e97193.
  48. Harries AD, Fitzsimons E, Fifield R, et al. Platelet count: a simple measure of activity in Crohn's disease. Br Med J (Clin Res Ed). 1983; 286(6376): 1476.
  49. Li L, Xu P, Zhang Z, et al. Platelets can reflect the severity of Crohn's disease without the effect of anemia. Clinics (Sao Paulo). 2020; 75: e1596.
  50. Collins CE, Rampton DS. Review article: platelets in inflammatory bowel disease — pathogenetic role and therapeutic implications. Aliment Pharmacol Ther. 1997; 11(2): 237–247.
  51. Yan SLS, Russell J, Harris NR, et al. Platelet abnormalities during colonic inflammation. Inflamm Bowel Dis. 2013; 19(6): 1245–1253.
  52. Brazil JC, Louis NA, Parkos CA. The role of polymorphonuclear leukocyte trafficking in the perpetuation of inflammation during inflammatory bowel disease. Inflamm Bowel Dis. 2013; 19(7): 1556–1565.
  53. Balmus IM, Ciobica A, Trifan A, et al. The implications of oxidative stress and antioxidant therapies in Inflammatory Bowel Disease: Clinical aspects and animal models. Saudi J Gastroenterol. 2016; 22(1): 3–17.
  54. Guan G, Lan S. Implications of Antioxidant Systems in Inflammatory Bowel Disease. Biomed Res Int. 2018; 2018: 1290179.
  55. Ighodaro OM, Akinloye OA. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alexandria J M. 2019; 54(4): 287–293.
  56. Docamo R, Moreno SNJ. 17 — Biochemistry of Tryanosoma cruzi. In: Telleria J, Tibayrenc M. ed. American Tryanosomiasis Chagas Disease. 2nd ed. Elsevier, London 2017: 371–400.
  57. Biasi F, Leonarduzzi G, Oteiza PI, et al. Inflammatory bowel disease: mechanisms, redox considerations, and therapeutic targets. Antioxid Redox Signal. 2013; 19(14): 1711–1747.
  58. Hao G, Xu Z, Li Li. Manipulating extracellular tumour pH: an effective target for cancer therapy. RSC Adv. 2018; 8(39): 22182–22192.
  59. Mårtensson J, Jain A, Meister A. Glutathione is required for intestinal function. Proc Natl Acad Sci USA. 1990; 87(5): 1715–1719.
  60. Babbs CF. Oxygen radicals in ulcerative colitis. Free Radic Biol Med. 1992; 13(2): 169–181.
  61. Joo M, Kim HS, Kwon TH, et al. Anti-inflammatory Effects of Flavonoids on TNBS-induced Colitis of Rats. Korean J Physiol Pharmacol. 2015; 19(1): 43–50.
  62. Hansberry DR, Shah K, Agarwal P, et al. Fecal Myeloperoxidase as a Biomarker for Inflammatory Bowel Disease. Cureus. 2017; 9(1): e1004.
  63. Lau D, Baldus S. Myeloperoxidase and its contributory role in inflammatory vascular disease. Pharmacol Ther. 2006; 111(1): 16–26.
  64. Pattison DI, Davies MJ. Reactions of myeloperoxidase-derived oxidants with biological substrates: gaining chemical insight into human inflammatory diseases. Curr Med Chem. 2006; 13(27): 3271–3290.
  65. Barone FC, Hillegass LM, Tzimas MN, et al. Time-related changes in myeloperoxidase activity and leukotriene B4 receptor binding reflect leukocyte influx in cerebral focal stroke. Mol Chem Neuropathol. 1995; 24(1): 13–30.
  66. Antoniou E, Margonis GA, Angelou A, et al. The TNBS-induced colitis animal model: An overview. Ann Med Surg (Lond). 2016; 11: 9–15.
  67. Lau D, Mollnau H, Eiserich JP, et al. Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins. Proc Natl Acad Sci U S A. 2005; 102(2): 431–436.
  68. Khalatbary AR, Ahmadvand H. Effect of oleuropein on tissue myeloperoxidase activity in experimental spinal cord trauma. Iran Biomed J. 2011; 15(4): 164–167.
  69. Fiorucci S, Distrutti E, Mencarelli A, et al. Inhibition of intestinal bacterial translocation with rifaximin modulates lamina propria monocytic cells reactivity and protects against inflammation in a rodent model of colitis. Digestion. 2002; 66(4): 246–256.
  70. Tian T, Wang Z, Zhang J. Pathomechanisms of Oxidative Stress in Inflammatory Bowel Disease and Potential Antioxidant Therapies. Oxid Med Cell Longev. 2017; 2017: 4535194.
  71. Mencarelli A, Renga B, Palladino G, et al. Inhibition of NF-κB by a PXR-dependent pathway mediates counter-regulatory activities of rifaximin on innate immunity in intestinal epithelial cells. Eur J Pharmacol. 2011; 668(1-2): 317–324.
  72. Banan A, Choudhary S, Zhang Y, et al. Ethanol-induced barrier dysfunction and its prevention by growth factors in human intestinal monolayers: evidence for oxidative and cytoskeletal mechanisms. J Pharmacol Exp Ther. 1999; 291(3): 1075–1085.
  73. Rao R, Baker RD, Baker SS. Inhibition of oxidant-induced barrier disruption and protein tyrosine phosphorylation in Caco-2 cell monolayers by epidermal growth factor. Biochem Pharmacol. 1999; 57(6): 685–695.
  74. Sartor RB. Review article: the potential mechanisms of action of rifaximin in the management of inflammatory bowel diseases. Aliment Pharmacol Ther. 2016; 43 Suppl 1: 27–36.
  75. Liu X, Wang J. Anti-inflammatory effects of iridoid glycosides fraction of Folium syringae leaves on TNBS-induced colitis in rats. J Ethnopharmacol. 2011; 133(2): 780–787.
  76. Song M, Xia B, Li J. Effects of topical treatment of sodium butyrate and 5-aminosalicylic acid on expression of trefoil factor 3, interleukin 1beta, and nuclear factor kappaB in trinitrobenzene sulphonic acid induced colitis in rats. Postgrad Med J. 2006; 82(964): 130–135.