Advertisement

AAPS PharmSciTech

, 20:112 | Cite as

Xylan from Pineapple Stem Waste: a Potential Biopolymer for Colonic Targeting of Anti-inflammatory Agent Mesalamine

  • Atsarina Larasati Anindya
  • Risa Dwi Oktaviani
  • Benita Rachel Praevina
  • Sophi Damayanti
  • Neng Fisheri Kurniati
  • Catur Riani
  • Heni RachmawatiEmail author
Research Article

Abstract

We have successfully conjugated mesalamine (5-aminosalicylic acid, 5-ASA) with xylan, a biopolymer isolated from pineapple stem waste, to form xylan-5-ASA conjugate. The biopolymer was used to provide colon-targeting properties for 5-ASA, a golden standard anti-inflammatory agent commonly used for ulcerative colitis treatment. A series of data from FTIR spectroscopy, UV-Vis spectrophotometry, and HPLC confirmed the xylan-5-ASA conjugate formation. To ensure successful colon targeting properties, in vitro and in vivo drug release studies after oral administration of xylan-5-ASA conjugate to Wistar rats were performed. Xylan-5-ASA conjugate was able to retain 5-ASA release in the upper gastrointestinal tract fluid simulation but rapidly released 5-ASA in the rat colon fluid simulation. In vivo release profile shows a very low peak plasma concentration, reached at 6 h after xylan-5-ASA conjugate administration. The delayed release and the lower bioavailability of 5-ASA from xylan-5-ASA conjugate administration compared to free 5-ASA administration confirmed the successful local colon delivery of 5-ASA using xylan-5-ASA conjugate. The administration of xylan-5-ASA conjugate also exhibited greater efficacy in recovering 2,4,6-trinitrobenzene sulfonic acid-induced colon ulcer compared to free 5-ASA administration. Taken together, xylan isolated from pineapple stem waste is promising to obtain colon targeting property for 5-ASA.

KEY WORDS

xylan 5-ASA colon targeting colonic drug delivery ulcerative colitis 

Notes

Acknowledgments

The project was financially supported by Bandung Institute of Technology (ITB) through “Innovative Research Grant” scheme year 2017.

Compliance with Ethical Standards

All institutional and national guidelines for the care and use of laboratory animals were followed. School of Pharmacy, Bandung Institute of Technology, Indonesia. The approval number is 305/UN6.C.10/PN/2017 (15/3/2017).

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12249_2018_1205_MOESM1_ESM.docx (19 kb)
ESM 1 (DOCX 18 kb)
12249_2018_1205_MOESM2_ESM.xlsx (38 kb)
ESM 2 (XLSX 38 kb)
12249_2018_1205_MOESM3_ESM.pdf (35 kb)
ESM 3 (PDF 34 kb)
12249_2018_1205_MOESM4_ESM.pdf (35 kb)
ESM 4 (PDF 34 kb)
12249_2018_1205_MOESM5_ESM.pdf (35 kb)
ESM 5 (PDF 34 kb)
12249_2018_1205_MOESM6_ESM.pdf (35 kb)
ESM 6 (PDF 35 kb)

References

  1. 1.
    Chen H. Chemical composition and structure of natural lignocellulose. In: Chen H, editor. Biotechnology of lignocellulose: theory and practice. Dordrecht: Springer; 2014. p. 25–71.CrossRefGoogle Scholar
  2. 2.
    da Silva AE, Marcelino HR, Gomes MCS, Oliveira EE, Nagashima T Jr, Egito EST. Xylan, a promising hemicellulose for pharmaceutical use. In: Verbeek CJR, editor. Products and applications of biopolymers. Rijeka: InTech; 2012. p. 62–5.Google Scholar
  3. 3.
    Scocca J, Lee YC. The composition and structure of the carbohydrate of pineapple stem bromelain. J Biol Chem. 1969;244(18):4852–63.PubMedGoogle Scholar
  4. 4.
    Oliveira EE, Silva AE, Júnior TN, Gomes MC, Aguiar LM, Marcelino HR, et al. Xylan from corn cobs, a promising polymer for drug delivery: production and characterization. Bioresour Technol. 2010;101(14):5402–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Scheline RR. Metabolism of foreign compounds by gastrointestinal microorganisms. Pharmacol Rev. 1973;25(4):451–523.PubMedGoogle Scholar
  6. 6.
    Sauraj, Kumar SU, Gopinath P, Negi YS. Synthesis and bio-evaluation of xylan-5-fluorouracil-1-acetic acid conjugates as prodrugs for colon cancer treatment. Carbohydr Polym. 2017;157:1442–3 1447–1449.PubMedCrossRefGoogle Scholar
  7. 7.
    Sauraj, Kumar SU, Kumar V, Priyadarshi R, Gopinath P, Negi YS. pH-responsive prodrug nanoparticles based on xylan-curcumin conjugate for the efficient delivery of curcumin in cancer therapy. Carbohydr Polym. 2018;188:252–3 256–257.PubMedCrossRefGoogle Scholar
  8. 8.
    Kong W, Gao C, Hu S, Ren J, Zhao L, Sun R. Xylan-modified-based hydrogels with temperature/pH dual sensitivity and controllable drug delivery behavior. Materials. 2017;10(304):1–3 9–10.Google Scholar
  9. 9.
    Rachmilewitz D, Karmeli F, Schwartz LW, Simon PL. Effect of aminophenols (5-ASA and 4-ASA) on colonic interleukin-1 generation. Gut. 1992;33(7):929–32.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Stevens C, Lipman M, Fabry S, Moscovitch-Lopatin M, Almawi W, Keresztes S, et al. 5-Aminosalicylic acid abrogates T-cell proliferation by blocking interleukin-2 production in peripheral blood mononuclear cells. J Pharmacol Exp Ther. 1995;272(1):399–406.PubMedGoogle Scholar
  11. 11.
    Peskar BM, Dreyling KW, May B, Schaarschmidt K, Goebell H. Possible mode of action of 5-aminosalicylic acid. Dig Dis Sci. 1987;32(12):51S–6S.PubMedCrossRefGoogle Scholar
  12. 12.
    Ahnfelt-Rønne I, Nielsen OH, Christensen A, Langholz E, Binder V, Riis P. Clinical evidence supporting the radical scavenger mechanism of 5-aminosalicylic acid. Gastroenterology. 1989;98(5):1162–9.CrossRefGoogle Scholar
  13. 13.
    Yamada T, Volkmer C, Grisham MB. Antioxidant properties of 5-ASA: potential mechanism for its anti-inflammatory activity. Can J Gastroenterol. 1990;4(7):295–302.CrossRefGoogle Scholar
  14. 14.
    Tama H, Kachur JF, Grisham MB, Gaginella TS. Scavenging effect of 5-aminosalicylic acid on neutrophil-derived oxidants: Possible contribution to the mechanism of action in inflammatory bowel disease. Biochem Pharmacol. 1991;41(6–7):1001–6.CrossRefGoogle Scholar
  15. 15.
    Iacucci M, de Silva S, Ghosh S. Mesalazine in inflammatory bowel disease: a trendy topic once again? Can J Gastroenterol. 2010;24(2):127–33.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Katz S, Lichtenstein GR, Safdi MA. 5-ASA dose-response, maximizing efficacy and adherence. Gastroenterol Hepatol. 2010;6(2):1–16.Google Scholar
  17. 17.
    Head KA, Jurenka JS. Inflammatory bowel disease part I: ulcerative colitis – pathophysiology and conventional and alternative treatment options. Altern Med Rev. 2003;8(3):247–83.PubMedGoogle Scholar
  18. 18.
    Gamboa JM, Leong KW. In vitro and in vivo models for the study of oral delivery of nanoparticles. Adv Drug Deliv Rev. 2013;65:800–10 Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773489/pdf/nihms453288.pdf.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    (724) Drug release. USP 38–NF 33. 38th ed. Rockville, MD: United States Pharmacopeial Convention; 2015. p. 497–504.Google Scholar
  20. 20.
    Dangi AA, Ganure AL, Divya J. Formulation and evaluation of colon targeted drug delivery system of levetiracetam using pectin as polymeric carrier. J Appl Pharm Sci. 2013;3:78–87.Google Scholar
  21. 21.
    Nair A, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016;7:27–31.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Rachmawati H, Pradana AT, Safitri D, Adnyana IK. Multiple functions of D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as curcumin nanoparticle stabilizer: in vivo kinetic profile and anti-ulcerative colitis analysis in animal model. Pharmaceutics. 2017;9(3):1–13.Google Scholar
  23. 23.
    Cooper HS, Murthy SN, Shah RS, Sedergran DJ. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Investig. 1993;69:238–49.PubMedGoogle Scholar
  24. 24.
    Zou M, Okamoto H, Cheng G, Hao X, Sun J, Cui F, et al. Synthesis and properties of polysaccharide prodrugs of 5-aminosalicylic acid as potential colon-specific delivery system. Eur J Pharm Biopharm. 2005;59:155–60.PubMedCrossRefGoogle Scholar
  25. 25.
    Kumar S, Negi YS. Corn cob xylan-based nanoparticles: ester prodrug of 5-aminosalicylic acid for possible targeted delivery of drug. J Pharm Sci Res. 2012;4(12):1995–2003.Google Scholar
  26. 26.
    Colom X, Carrillo F, Nogues F, Garriga P. Structural analysis of photodegraded wood by means of FTIR spectroscopy. Polym Degrad Stab. 2003;80(3):543–9.CrossRefGoogle Scholar
  27. 27.
    Dong MW. Modern HPLC for practicing scientist. Hoboken: Wiley; 2006.CrossRefGoogle Scholar
  28. 28.
    Macfarlane GT, Macfarlane S. Fermentation in the human large intestine: its physiologic consequences and the potential contribution of prebiotics. J Clin Gastroenterol. 2011;45:S120–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Rajesh A, Bharat C, Sangeeta A. Oral colon targeted drug delivery system: a review on current and novel perspectives. J Pharm Innov. 2012;1(5):6–12.Google Scholar
  30. 30.
    Honga P, Iakiviaka M, Dodd D, Zhanga M, Mackiea RI, Canna I. Two new xylanases with different substrate specificities from the human gut bacterium bacteroides intestinalis DSM 17393. Appl Environ Microbiol. 2014;80(7):2084–93.CrossRefGoogle Scholar
  31. 31.
    Bondesen S, Rasmussen SN, Madsen JR, Nielsen OH, Lauritsen K, Binder V, et al. 5-aminosalicylic acid in the treatment of inflammatory bowel disease. Acta Med Scand. 1987;221:227–42.PubMedCrossRefGoogle Scholar
  32. 32.
    Molavi DW. The practice of surgical pathology: a beginner’s guide to the diagnostic process. Cham: Springer International Publishing AG; 2018. p. 74.Google Scholar
  33. 33.
    Brynskov J, Nielsen OH, Ahnfelt-Rønne I, Bendtzen K. Cytokines (immunoinflammatory hormones) and their natural regulation in inflammatory bowel disease (Crohn's disease and ulcerative colitis): a review. Dig Dis. 1994;12(5):290–304.PubMedCrossRefGoogle Scholar
  34. 34.
    Wang N, Liang H, Zen K. Molecular mechanisms that influence the macrophage m1-m2 polarization balance. Front Immunol. 2014;5:614.PubMedPubMedCentralGoogle Scholar
  35. 35.
    Neeb L, Hellen P, Boehnke C, Hoffmann J, Schuh-Hofer S, Dirnagl U, et al. IL- 1β stimulates COX-2 dependent PGE2 synthesis and CGRP release in rat trigeminal ganglia cells. PLoS One. 2011;6(3):1–9.CrossRefGoogle Scholar
  36. 36.
    Ren K, Torres R. Role of interleukin- 1β during pain and inflammation. Brain Res Rev. 2008;60(1):57–64.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Wang D, DuBois RN. The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene. 2010;29(6):781–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2.  https://doi.org/10.1038/sigtrans.2017.23.

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Atsarina Larasati Anindya
    • 1
  • Risa Dwi Oktaviani
    • 2
  • Benita Rachel Praevina
    • 2
  • Sophi Damayanti
    • 2
  • Neng Fisheri Kurniati
    • 2
  • Catur Riani
    • 2
  • Heni Rachmawati
    • 2
    Email author
  1. 1.Research Center for Nanosciences and NanotechnologyBandung Institute of TechnologyBandungIndonesia
  2. 2.School of Pharmacy, Research Center for Nanosciences and NanotechnologyBandung Institute of TechnologyBandungIndonesia

Personalised recommendations