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Hydrogels from xylan/chitosan complexes for the controlled release of diclofenac sodium

  • Carla N. Schnell
  • María V. Galván
  • Miguel A. Zanuttini
  • Paulina MocchiuttiEmail author
Original Research


Hydrogels were prepared from colloidal suspensions of polyelectrolyte complexes of xylan (Xyl) and chitosan (Ch) (mass ratio: 70 wt% Xyl/30 wt% Ch). They were formed at pH 5.0, at which both polyelectrolytes were highly charged according to their corresponding potentiometric titrations. They were treated with a polycarboxylic acid, sodium citrate, at different concentrations (0%, 3% and 7% w/v), and characterized by means of FTIR, scanning electron microscopy, wet-mechanical properties, swelling and solubility. FTIR spectra confirmed the presence of sodium citrate in the treated hydrogels. Wet-stress and wet-strain at break were increased by 150% and 57% respectively, when hydrogels were treated with 7% w/v of sodium citrate. The swelling capacity was clearly modified due to the presence of this compound and to the ionic strength of the liquid medium. The ability of these hydrogels for drug loading and controlled release was studied in vitro using diclofenac sodium (DS) as model drug. It was found that at pH 7.4, the hydrogel treated with sodium citrate absorbed significantly higher amounts of diclofenac sodium (up to 255 mg DS/g hydrogel) and its release was better controlled compared to that of the non-treated hydrogel. Particularly, the presence of sodium citrate in the liquid medium after the diclofenac sodium loading process and the influence of the ionic strength on the drug release rate indicated that an ion exchange process occurred, first between sodium citrate and diclofenac sodium and then between this drug and the ions present in the solution.

Graphic abstract


Sodium citrate treatments Ion exchange Anionic drug Wet strength properties Hemicelluloses 



The authors wish to acknowledge the financial support received from ANPCyT—PICT 2013 N°2212; CONICET-PIP 2013-2015 GI N°: 11220120100672CO; CAI + D 2012 N°500 201101 00057. Thanks are also given to Gabriel Exequiel Ramella for his help in the laboratory.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Ahmadi F, Oveisi Z, Samani S, Amoozgar Z (2015) Chitosan based hydrogels: characteristics and pharmaceutical applications. Res Pharm Sci 10(1):1–16CrossRefGoogle Scholar
  2. Andrade-Vivero P, Fernandez-Gabriel E, Alvarez-Lorenzo C, Concheiro A (2007) Improving the loading and release of NSAIDs from pHEMA Hydrogels by copolymerization with functionalized monomers. J Pharm Sci 96(4):802–813. CrossRefPubMedGoogle Scholar
  3. Batycky RP, Hanes J, Langer R, Edwars DA (1997) A theoretical model of erosion and macromolecular drug release from biodegrading microspheres. J Pharm Sci 86(12):1464–1477. CrossRefPubMedGoogle Scholar
  4. Berger J, Reist M, Mayer JM, Felt O, Peppas NA, Gurny R (2004) Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications. Eur J Pharm Biopharm 57(1):19–34. CrossRefPubMedGoogle Scholar
  5. Bush JR, Liang H, Dickinson M, Botchwey EA (2016) Xylan hemicellulose improves chitosan hydrogel for bone tissue regeneration. Polym Adv Technol 27(8):1050–1055. CrossRefPubMedPubMedCentralGoogle Scholar
  6. Caló E, Khutoryanskiy VV (2015) Biomedical applications of hydrogels: a review of patents and commercial products. Eur Polym J 65:252–267. CrossRefGoogle Scholar
  7. Chen H, Hu X, Chen E, Wu S, McClements DJ, Liu S, Li B, Li Y (2016) Preparation, characterization, and properties of chitosan films with cinnamaldehyde nanoemulsions. Food Hydrocoll 61(662–6):71. CrossRefGoogle Scholar
  8. Cursaru B, Teodorescu M, Boscornea C, Stanescu PO, Stoleriu S (2013) Drug absorption and release properties of crosslinked hydrogels based on diepoxy-terminated poly(ethylene glycol)s and aliphatic polyamines—A study on the effect of the gel molecular structure. Mater Sci Eng C 33(3):1307–1314. CrossRefGoogle Scholar
  9. Dadsetan M, Taylor KE, Yong C, Bajzer Ž, Lichun L, Yaszemski MJ (2013) Controlled release of doxorubicin from pH-responsive microgels. Acta Biomater 9:5438–5446. CrossRefPubMedGoogle Scholar
  10. Don T-M, Huang M-L, Chiu A-C, Kuo K-H, Chiu W-Y, Chiu L-H (2008) Preparation of thermo-responsive acrylic hydrogels useful for the application in transdermal drug delivery systems. Mater Chem Phys 107(2–3):266–273. CrossRefGoogle Scholar
  11. Draget KI, Värum KM, Moen E, Gynnild H, Smidsrød O (1992) Chitosan cross-linked with Mo (VI) polyoxyanions: a new gelling system. Biomaterials 13(9):635–638. CrossRefPubMedGoogle Scholar
  12. Drury JL, Mooney DJ (2003) Hydrogels for tissue engineering: scaffold design variables and applications, review. Biomaterials 24(24):4337–4351. CrossRefPubMedGoogle Scholar
  13. Esteban SL, Manzo RH, Alovero FL (2009) Azithromycin loaded on hydrogels of carbomer: chemical stability and delivery properties. Int J Pharm 366:53–57. CrossRefPubMedGoogle Scholar
  14. Gabrielii I, Gatenholm P, Glasser WG, Jain RK, Kenne L (2000) Separation, characterization and hydrogel-formation of hemicellulose from aspen wood. Carbohydr Polym 43(4):367–374. CrossRefGoogle Scholar
  15. Gabrielli I, Gatenholm P (1998) Preparation and properties of hydrogels based on hemicellulose. J Appl Polym Sci 69:1661–1667.;2-X CrossRefGoogle Scholar
  16. Galván MV, Mocchiutti P, Cornaglia LM, Zanuttini MA (2012) Dual-polyelectrolyte adsorption of poly(allylamine hydrochloride) and xylan onto recycled unbleached fibers. BioResources 7(2):2075–2089CrossRefGoogle Scholar
  17. García MC (2018) Ionic-strength-responsive polymers for drug delivery applications. In: Makhlouf AS, Abu-Thabit NY (eds) Stimuli responsive polymeric nanocarriers for drug delivery applications, 1st edn. Elsevier, Amsterdam, pp 393–409. CrossRefGoogle Scholar
  18. Gupta P, Vermani K, Garg S (2002) Hydrogels: from controlled release to pH-responsive drug delivery, review. Drug Discov Today 7(10):569–579. CrossRefPubMedGoogle Scholar
  19. Hamman JH (2010) Chitosan based polyelectrolyte complexes as potential carrier materials in drug delivery systems, review. Mar Drugs 8(4):1305–1322. CrossRefPubMedPubMedCentralGoogle Scholar
  20. Huang X, Brazel CS (2001) On the importance and mechanisms of burst release in matrix-controlled drug delivery systems, review. J Control Release 73(2–3):121–136. CrossRefPubMedGoogle Scholar
  21. Ikeda S, Kumagai H, Sakiyama T, Chu C-H, Nakamura K (1995) Method for analyzing pH-sensitive swelling of amphoteric hydrogels—application to a polyelectrolyte complex gel prepared from Xanthan and Chitosan. Biosci Biotech Biochem 59(8):1422–1427. CrossRefGoogle Scholar
  22. Jeong B, Bae YH, Kim SW (2000) Drug release from biodegradable injectable thermosensitive hydrogel of PEG–PLGA–PEG triblock copolymers. J Control Release 63(1–2):155–163. CrossRefPubMedGoogle Scholar
  23. Karaaslan MA, Tshabalala MA, Buschle-Diller G (2010) Wood hemicellulose/chitosan-based semi-interpenetrating network hydrogels: mechanical, swelling, and controlled drug release properties. BioResources 5(2):1036–1054Google Scholar
  24. Karaaslan MA, Tshabalala MA, Buschle-Diller G (2012) Semi-interpenetrating polymer network hydrogels based on aspen hemicellulose and chitosan: effect of crosslinking sequence on hydrogel properties. J Appl Polym Sci 124:1168–1177. CrossRefGoogle Scholar
  25. Khazaeinia T, Jamali F (2003) A comparison of gastrointestinal permeability induced by diclofenac-phospholipid complex with diclofenac acid and its sodium salt. J Pharm Pharm Sci 6(3):352–359PubMedGoogle Scholar
  26. Kim S, Chu C (2000) Synthesis and characterization of dextran-methacrylate hydrogels and structural study by SEM. J Biomed Res.;2-8 CrossRefGoogle Scholar
  27. Kim B, Peppas NA (2003) In vitro release behavior and stability of insulin in complexation hydrogels as oral drug delivery carriers. Int J Pharm 266:29–37. CrossRefPubMedGoogle Scholar
  28. Kim SW, Bae YH, Okano T (1992) Hydrogels: swelling, drug loading, and release, pharmaceutical research, review. Pharm Res 9(3):283–290CrossRefGoogle Scholar
  29. Krukowski S, Karasiewicz M, Kolodziejski W (2017) Convenient UV-spectrophotometric determination of citrates in aqueous solutions with applications in the pharmaceutical analysis of oral electrolyte formulations. J Food Drug Anal 25(3):717–722. CrossRefPubMedGoogle Scholar
  30. Kumar S, Negi YS (2014) Cellulose and xylan based prodrug of diclofenac sodium: synthesis, physicochemical characterization and in vitro release. Int J Polym Mater Polym Biomater 63(6):283–292. CrossRefGoogle Scholar
  31. Laine J, Buchert J, Viikari L, Stenius P (1996) Characterization of unbleached kraft pulps by enzymatic treatment, potentiometric titration and polyelectrolyte adsorption. Holzforschung 50(3):208–214. CrossRefGoogle Scholar
  32. Lankalapalli S, Kolapalli VR (2009) Polyelectrolyte complexes: a review of their applicability in drug delivery technology. Indian J Pharm Sci 71(5):481–487. CrossRefPubMedPubMedCentralGoogle Scholar
  33. Li X, Shi X, Wang M, Du Y (2011) Xylan chitosan conjugate—a potential food preservative. Food Chem 126(2):520–525. CrossRefGoogle Scholar
  34. Linder Å, Bergman R, Bodin A, Gatenholm P (2003) Mechanism of assembly of xylan onto cellulose surface. Langmuir 19(12):5072–5077. CrossRefGoogle Scholar
  35. Mi FL, Chen CT, Tseng YC, Kuan CY, Shyu SS (1997) Iron (III)-carboxymethylchitin microsphere for the pH-sensitive release of 6-mercaptopurine. J Control Release 44(1):19–32. CrossRefGoogle Scholar
  36. Mocchiutti P, Schnell CN, Rossi GD, Peresin MS, Zanuttini MA, Galván MV (2016) Cationic and anionic polyelectrolyte complexes of xylan and chitosan. Interaction with lignocellulosic surfaces. Carbohydr Polym 150:89–98. CrossRefPubMedGoogle Scholar
  37. Palena MC, García MC, Manzo RH, Jimenez-Kairuz AF (2015) Self-organized drug- interpolyelectrolyte nanocomplexes loaded with anionic drugs. Characterization and in vitro release evaluation. J Drug Deliv Sci Technol 30:45–53. CrossRefGoogle Scholar
  38. Qiu Y, Park K (2012) Environment-sensitive hydrogels for drug delivery. Adv Drug Deliv Rev 64:49–60. CrossRefGoogle Scholar
  39. Rinaudo M (2006) Chitin and chitosan: properties and applications. Progr Polym Sci 31(7):603–632. CrossRefGoogle Scholar
  40. Sacco P, Borgogna M, Travan A, Marsich E, Paoletti S, Asaro F, Donati I (2014) Polysaccharide-based networks from homogeneous chitosan-tripolyphosphate hydrogels: synthesis and characterization. Biomacromol 15(9):3396–3405. CrossRefGoogle Scholar
  41. Schnell CN, Galván MV, Peresin MS, Inalbon MC, Vartiainen J, Zanuttini MA, Mocchiutti P (2017) Films from xylan/chitosan complexes: preparation and characterization. Cellulose 24(10):4393–4403. CrossRefGoogle Scholar
  42. Shi R, Bi J, Zhang Z, Zhu A, Chen D, Zhou X, Zhang L, Tian W (2008) The effect of citric acid on the structural properties and cytotoxicity of the polyvinyl alcohol/starch films when molding at high temperature. Carbohydr Polym 74(4):763–770. CrossRefGoogle Scholar
  43. Shu XZ, Zhu KJ, Song W (2001) Novel pH-sensitive citrate cross-linked chitosan film for drug controlled release. Int J Pharm 212(1):19–28. CrossRefPubMedGoogle Scholar
  44. Sjöström E (1993) Wood chemistry. Fundamentals and applications. In: Sjöström E (ed) Wood polysaccharides, 2nd edn. Academic Press Inc., California, San Diego, pp 51–70Google Scholar
  45. Skoog DA, Holler FJ, Neiman TA (2001) Principios de análisis instrumental. McGraw-Hill Interamericana de España SL, MadridGoogle Scholar
  46. Tan W-H, Takeuchi S (2007) Monodisperse alginate hydrogel microbeads for cell encapsulation. Adv Mater 19:2696–2701. CrossRefGoogle Scholar
  47. Tarvainen T, Svarfvar B, Åkerman S, Savolainen J, Karhu M, Paronen P, Järvinen K (1999) Drug release from a porous ion-exchange membrane in vitro. Biomaterials 20(22):2177–2183. CrossRefPubMedGoogle Scholar
  48. Wang Q, Zhang J, Wang A (2009) Preparation and characterization of a novel pH-sensitive chitosan-g-poly(acrylic acid)/attapulgite/sodium alginate composite hydrogel bead for controlled release of diclofenac sodium. Carbohydr Polym 78:731–737. CrossRefGoogle Scholar
  49. Wang H, Qian C, Roman M (2011) Effects of pH and salt concentration on the formation and properties of chitosan-cellulose nanocrystal polyelectrolyte-macroion complexes. Biomacromol 12(10):3708–3714. CrossRefGoogle Scholar
  50. Wu T, Li Y, Lee DS (2017) Chitosan-based composite hydrogels for biomedical applications. Macromol Res 25(6):480–488. CrossRefGoogle Scholar

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© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Instituto de Tecnología Celulósica, Facultad de Ingeniería Química (FIQ-CONICET)Universidad Nacional del LitoralSanta FeArgentina

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