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.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
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.
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.
Scocca J, Lee YC. The composition and structure of the carbohydrate of pineapple stem bromelain. J Biol Chem. 1969;244(18):4852–63.
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.
Scheline RR. Metabolism of foreign compounds by gastrointestinal microorganisms. Pharmacol Rev. 1973;25(4):451–523.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Katz S, Lichtenstein GR, Safdi MA. 5-ASA dose-response, maximizing efficacy and adherence. Gastroenterol Hepatol. 2010;6(2):1–16.
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.
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.
(724) Drug release. USP 38–NF 33. 38th ed. Rockville, MD: United States Pharmacopeial Convention; 2015. p. 497–504.
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.
Nair A, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016;7:27–31.
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.
Cooper HS, Murthy SN, Shah RS, Sedergran DJ. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Investig. 1993;69:238–49.
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.
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.
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.
Dong MW. Modern HPLC for practicing scientist. Hoboken: Wiley; 2006.
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.
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.
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.
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.
Molavi DW. The practice of surgical pathology: a beginner’s guide to the diagnostic process. Cham: Springer International Publishing AG; 2018. p. 74.
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.
Wang N, Liang H, Zen K. Molecular mechanisms that influence the macrophage m1-m2 polarization balance. Front Immunol. 2014;5:614.
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.
Ren K, Torres R. Role of interleukin- 1β during pain and inflammation. Brain Res Rev. 2008;60(1):57–64.
Wang D, DuBois RN. The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene. 2010;29(6):781–8.
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.
The project was financially supported by Bandung Institute of Technology (ITB) through “Innovative Research Grant” scheme year 2017.
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.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Anindya, A.L., Oktaviani, R.D., Praevina, B.R. et al. Xylan from Pineapple Stem Waste: a Potential Biopolymer for Colonic Targeting of Anti-inflammatory Agent Mesalamine. AAPS PharmSciTech 20, 112 (2019). https://doi.org/10.1208/s12249-018-1205-y
- colon targeting
- colonic drug delivery
- ulcerative colitis