Interpenetrating Polymer Network Hydrogels of Chitosan: Applications in Controlling Drug Release

  • Dilipkumar PalEmail author
  • Amit Kumar Nayak
  • Supriyo Saha
Living reference work entry
Part of the Polymers and Polymeric Composites: A Reference Series book series (POPOC)


Chitosan is a natural polysaccharide obtained by alkaline deacetylation of chitin. It is cationic in ionic nature. Because of its biocompatibility and biodegradability, chitosan is employed as a drug carrier material in the development of various kinds of drug delivery. However, the extensive use of chitosan as a drug delivery carrier material is limited by its rapid dissolution in the acidic pH of the stomach, and this causes restrictions in controlling drug release from chitosan-based oral dosage forms. To overcome this limitation, modifications of chitosan to develop hydrogel systems are being investigated by researchers. Among these modified chitosan-based hydrogel systems, interpenetrated polymer network (IPN) hydrogels have enhanced mechanical properties at gastric pH, as well as improved control of drug release over a longer period. This chapter describes the preparations and properties, in terms of drug-releasing performance, of various chitosan-based IPN hydrogels for controlling drug release.


Chitosan Interpenetrating polymer network (IPN) Hydrogel Oral dosage forms Drug release 


  1. 1.
    Mohamed EIB, Entsar IR (2011) A biopolymer chitosan and its derivatives as promising antimicrobial agents against plant pathogens and their applications in crop protection. Int J Carbohydr Chem 2011:1–29. Scholar
  2. 2.
    Randy CFC, Tzi BN, Jack HW, Wai YC (2015) Chitosan: an update on potential biomedical and pharmaceutical applications. Mar Drugs 13:5156–5186CrossRefGoogle Scholar
  3. 3.
    Shweta A, Ankita L, Aakriti T, Vijay K, Imran M, Anita KV (2015) Versatility of chitosan: a short review. J Pharm Res 4(3):125–134Google Scholar
  4. 4.
    Manish PP, Ravi RP, Jayvadan KP (2010) Chitosan mediated targeted drug delivery system: a review. J Pharm Pharm Sci 3(3):536–557Google Scholar
  5. 5.
    Arya S, Flowerlet M, Chacko AJ, Mini A, Poosan GV (2014) Interpenetrating polymer network (IPN) – hydrogels. Pharma Innov J 3(8):59–66Google Scholar
  6. 6.
    Mohd FQ, Rishabha M, Pramod KS (2015) Biomedical applications of interpenetrating polymer network system. Open Pharm Sci J 2:21–30CrossRefGoogle Scholar
  7. 7.
    Vineet B, Gargi H, Sokindra K (2012) Interpenetrating polymer network (IPN): novel approach in drug delivery. Int J Drug Dev Res 4(3):41–54Google Scholar
  8. 8.
    Duncan R (2012) The dawning era of polymer therapeutics. Nat Rev Drug Discov 2:347–360CrossRefGoogle Scholar
  9. 9.
    Duncan R (2006) Polymer conjugates for drug targeting. From inspired to inspiration! J Drug Target 14:333–335CrossRefPubMedGoogle Scholar
  10. 10.
    Pangburn SH, Trescony PV, Heller J (1982) Lysozyme degradation of partially deacetylated chitin, its films and hydrogels. Biomaterials 3(2):105–108CrossRefPubMedGoogle Scholar
  11. 11.
    Martins AF, Facchi SP, Follmann HD, Pereira AG, Rubira AF, Muniz EC (2014) Antimicrobial activity of chitosan derivatives containing N-quaternized moieties in its backbone: a review. Int J Mol Sci 15:20800–200832CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kumari K, Kundu PP (2008) Studies on in vitro release of CPM from semi-interpenetrating polymer network (IPN) composed of chitosan and glutamic acid. Bull Mater Sci 31:159–167CrossRefGoogle Scholar
  13. 13.
    Gupta AK, Maurya SD, Dhakar RC, Singh RD (2010) pH sensitive interpenetrating hydrogel for eradication of Helicobacter pylori. Int J Pharm Sci Nanotechnol 3:924–932Google Scholar
  14. 14.
    Dogra S (2011) A chitosan–polymer hydrogel bead system for a metformin HCI controlled release oral dosage form. PhD theses and dissertations, The University of Toledo Digital Repository, pp 1–92Google Scholar
  15. 15.
    Subhash SV, Madhabhai M (2011) Hydrogels based on interpenetrating network of chitosan and polyvinyl pyrrolidone for pH-sensitive delivery of repaglinide. Curr Drug Discov Technol 8:126–135CrossRefGoogle Scholar
  16. 16.
    Bahman VF, Hossein G, Shiravan A (2016) Intelligent semi-IPN chitosan–PEG–PAAm hydrogel for closed-loop insulin delivery and kinetic modeling. RSC Adv 6(32):26590–26598CrossRefGoogle Scholar
  17. 17.
    Nazar MR, Gohar A, Shahzad A, Muhammad TA (2010) Preparation and characterization of hybrid pH-sensitive hydrogels of chitosan-co-acrylic acid for controlled release of verapamil. J Mater Sci Mater Med 21:2805–2816CrossRefGoogle Scholar
  18. 18.
    Yang J, Chen J, Pan D, Wan Y, Wang Z (2013) pH-sensitive interpenetrating network hydrogels based on chitosan derivatives and alginate for oral drug delivery. Carbohydr Polym 92:719–725CrossRefPubMedGoogle Scholar
  19. 19.
    Nayak A, Pal D (2012) Ionotropically-gelled mucoadhesive beads for oral metformin HCl delivery: formulation, optimization and antidiabetic evaluation. J Sci Ind Res 72:851–858Google Scholar
  20. 20.
    Kemal B, Ayse ZA, Zelal A, Bahattin MB (2013) Chitosan/alginate crosslinked hydrogels: preparation, characterization and application for cell growth purposes. Int J Biol Macromol 59:342–348CrossRefGoogle Scholar
  21. 21.
    Chen R, Chen Q, Huo D, Ding Y, Hu Y, Jiang X (2012) In situ formation of chitosan–gold hybrid hydrogel and its application for drug delivery. Colloids Surf B Biointerfaces 97:132–137CrossRefPubMedGoogle Scholar
  22. 22.
    Pal D, Nayak A (2012) Novel tamarind seed polysaccharide–alginate mucoadhesive microspheres for oral gliclazide delivery: in vitro–in vivo evaluation. Drug Deliv 19:123–131CrossRefPubMedGoogle Scholar
  23. 23.
    Marek K, Marek K, Małgorzata S, Aleksandra P, Ewa L, Aleksandra M, Agnieszka A, Aleksandra K (2016) Hydrogels made from chitosan and silver nitrate. Carbohydr Polym 140:74–87CrossRefGoogle Scholar
  24. 24.
    Garcia J, Ruiz-Durantez E, Valderruten NE (2017) Interpenetrating polymer networks hydrogels of chitosan and poly(2-hydroxyethyl methacrylate) for controlled release of quetiapine. React Funct Polym 117:52–59CrossRefGoogle Scholar
  25. 25.
    Nayak AK, Pal D, Malakar J (2012) Development, optimization and evaluation of floating beads using natural polysaccharides blend for controlled drug release. Polym Eng Sci 53:238–250CrossRefGoogle Scholar
  26. 26.
    Nayak A, Pal D (2011) Development of pH sensitive tamarind seed polysaccharide alginate composite beads for controlled diclofenac sodium delivery using response surface methodology. Int J Biol Macromol 49:784–793CrossRefPubMedGoogle Scholar
  27. 27.
    Aminabhavi TM, Dharupaneedi SP (2017) Production of chitosan-based hydrogels for biomedical applications. In: Chitosan based biomaterials. Woodhead Publishing, Sciencedirect. vol 1. pp 295–319Google Scholar
  28. 28.
    Banerjee S, Siddiqui L, Bhattacharya SS, Kaity S, Ghosh A, Chattopadhyay P, Pandey A, Singh L (2012) Interpenetrating polymer network (IPN) hydrogel microspheres for oral controlled release application. Int J Biol Macromol 50:198–206CrossRefPubMedGoogle Scholar
  29. 29.
    Hosseinzadeh H (2012) Synthesis of a novel interpenetrating polymer network hydrogel as drug delivery system. Adv Environ Biol 6(3):1079–1081Google Scholar
  30. 30.
    Bhattacharya SS, Mishra A, Pal D, Ghosh AK, Ghosh A, Banerjee S, Sen KK (2012) Synthesis and characterization of poly(acrylic acid)/poly(vinyl alcohol)–xanthan gum interpenetrating network (IPN) superabsorbent polymeric composites. Polym-Plast Technol Eng 51:876–882CrossRefGoogle Scholar
  31. 31.
    Nayak AK, Pal D (2015) Polymeric hydrogels as smart biomaterials. Part of the springer series on polymer and composite materials book series (SSPCM). Springer. Nature Switzerland AG. pp 105–151Google Scholar
  32. 32.
    Nayak AK, Pal D (2016) Sterculia gum–based hydrogels for drug delivery applications. In: Polymeric hydrogels as smart biomaterials. Springer series on polymer and composite materials. Springer. Nature Switzerland AG. pp 105–151Google Scholar
  33. 33.
    Fahad SAM, Sajjad H, Muhammad O, Adnan H, Tahseen K, Waheed AA, Muhammad J, Salah UDK (2016) Preparation of the chitosan/polyacrylonitrile semi-IPN hydrogel via glutaraldehyde vapors for the removal of Rhodamine B dye. Polym Bull 74:1535–1551Google Scholar
  34. 34.
    Nagahama H, Maeda H, Kashiki T, Jayakumar R, Furuike T, Tamura H (2009) Preparation and characterization of novel chitosan/gelatin membranes using chitosan hydrogel. Carbohydr Polym 76:255–260CrossRefGoogle Scholar
  35. 35.
    Fahanwi AN, Mustafa G, Akeem AO (2016) Adsorptive removal of multi-azo dye from aqueous phase using a semi-IPN superabsorbent chitosan–starch hydrogel. Chem Eng Res Des 112:274–288CrossRefGoogle Scholar
  36. 36.
    Yu X, Tao G, Ying J, Yapin W, Zezhang TW, Shaobing Z, Chongyun B, Xiaoming X (2016) Fabrication and characterization of a glucose-sensitive antibacterial chitosan polyethylene oxide hydrogel. Polymer 82:1–10CrossRefGoogle Scholar
  37. 37.
    Pal D, Mandal M, Senthilkumar GP, Padhiari A (2006) Antibacterial activity of methanol extract of Cuscuta reflexa Roxb. stem and Corchorus olitorius Linn. seed. Fitoterapia 77:589–591CrossRefPubMedGoogle Scholar
  38. 38.
    Mohanta TK, Patra JK, Rath SK, Pal D, Thatoi HN (2007) Evaluation of antimicrobial activity and phytochemical screening of oils and nuts of Semicarpus anacardium L. Sci Res Essays 2:486–490Google Scholar
  39. 39.
    Wen BW, Da JH, Yu RK, Wang AQ (2013) One-step in situ fabrication of a granular semi-IPN hydrogel based on chitosan and gelatin for fast and efficient adsorption of Cu2+ ion. Colloids Surf B Biointerfaces 106:51–59CrossRefGoogle Scholar
  40. 40.
    Xiaohong W, Haiqian H, Yujun L, Yingying W, Chen H, Cunwang G (2016) A novel semi-IPN hydrogel: preparation, swelling properties and adsorption studies of Co (II). J Ind Eng Chem 41:82–90CrossRefGoogle Scholar
  41. 41.
    Chena J, Suna J, Liming Y, Qunfei Z, Huina Z, Huifeng W, Allan SH, Isao K (2007) Preparation and characterization of a novel IPN hydrogel membrane of poly(N-isopropylacrylamide)/carboxymethyl chitosan (PNIPAAM/CMCS). Radiat Phys Chem 76:1425–1429CrossRefGoogle Scholar
  42. 42.
    Himadri SS, Ray SK (2014) Controlled release of tinidazole and theophylline from chitosan based composite hydrogels. Carbohydr Polym 106:109–120CrossRefGoogle Scholar
  43. 43.
    Mingzhen W, Yu F, Daodao H (2001) Preparation and properties of chitosan-poly(N-isopropylacrylamide) full-IPN hydrogels. React Funct Polym 48:215–221CrossRefGoogle Scholar
  44. 44.
    Daniela A, Luminita M, Simona M, Mihai M, Andra-Cristina B, Mariana P, Bogdan CS, Mihai B (2016) Dual crosslinked iminoboronate–chitosan hydrogels with strong antifungal activity against Candida planktonic yeasts and biofilms. Carbohydr Polym 152:306–316CrossRefGoogle Scholar
  45. 45.
    Hao Z, LiLi X, Yuezhong W, Kunde L, Xiaomei Z (2017) Ring-like structured chitosan–metal hydrogel: mass production, formation mechanism and applications. J Colloid Interface Sci 490:233–241CrossRefGoogle Scholar
  46. 46.
    Fazli W, Jun JY, Dong DX, Han X, Yu SL, Cheng Z, Li QC (2016) Synthesis and characterization of antibacterial carboxymethyl chitosan/ZnO nanocomposite hydrogels. Int J Biol Macromol 88:273–279CrossRefGoogle Scholar
  47. 47.
    Pal D, Nayak AK (2010) Nanotechnology for targeted delivery in cancer therapeutics. Int J Pharm Sci Rev Res 1:1–7Google Scholar
  48. 48.
    Abdur RA, Lubna S, Farah A, Khan AF, Chaudhry AA, Rehman I, Yar M (2017) Thyroxin releasing chitosan/collagen based smart hydrogels to stimulate neovascularization. Mater Des 133:416–425CrossRefGoogle Scholar
  49. 49.
    Jinke X, Mifong T, Sepideh S, Sophie L, Jake B, Mary MS, Marta C (2017) Mucoadhesive chitosan hydrogels as rectal drug delivery vessels to treat ulcerative colitis. Acta Biomater 48:247–257CrossRefGoogle Scholar
  50. 50.
    Nayak A, Pal D (2014) Trigonella foenum-graecum L. seed mucilage–gellan mucoadhesive beads for controlled release of metformin HCl. Carbohydr Polym 107:31–40CrossRefPubMedGoogle Scholar
  51. 51.
    Fatemeh Z, Pompilia I, Djahida D, Lojan S, Borhane A, Gilles S, Mircea AM, Sophie L (2017) Chitosan–doxycycline hydrogel: an MMP inhibitor/sclerosing embolizing agent as a new approach to endoleak prevention and treatment after endovascular aneurysm repair. Acta Biomater 64:94–105CrossRefGoogle Scholar
  52. 52.
    Nayak A, Pal D (2014) Ispaghula mucilage–gellan mucoadhesive polysaccharide–gellan mucoadhesive beads for controlled release of metformin HCl. Carbohydr Polym 103:41–50CrossRefGoogle Scholar
  53. 53.
    Nayak AK, Pal D (2015) Plant-derived polymers: ionically-gelled sustained drug release systems. In: Encyclopedia of biomedical polymers and polymer biomaterials. Taylor & Francis, New York, pp 6002–6017Google Scholar
  54. 54.
    Pal D, Nayak AK (2015) Alginate, blends and microspheres: controlled drug delivery. In: Encyclopedia of biomedical polymers and polymer biomaterials. Taylor & Francis, New York, pp 89–98CrossRefGoogle Scholar
  55. 55.
    Nayak A, Pal D (2014) Tamarind seed polysaccharide–gellan mucoadhesive beads for controlled release of metformin HCl. Carbohydr Polym 103:154–163CrossRefPubMedGoogle Scholar
  56. 56.
    Nayak A, Pal D (2014) Development of calcium pectinate–tamarind seed polysaccharide mucoadhesive beads containing metformin HCl. Carbohydr Polym 101:220–230CrossRefPubMedGoogle Scholar
  57. 57.
    Nayak A, Pal D, Das S (2013) Calcium pectinate–fenugreek seed mucilage mucoadhesive beads for controlled delivery of metformin HCl. Carbohydr Polym 96:349–357CrossRefPubMedGoogle Scholar
  58. 58.
    Nayak A, Pal D (2013) Fenugreek seed gum–alginate mucoadhesive beads of metformin HCl: design, optimization and evaluation. Int J Biol Macromol 54:144–154CrossRefPubMedGoogle Scholar
  59. 59.
    Pal D, Nayak A (2013) Statistical optimization and characterisation of potato starch blended alginate beads containing tolbutamide. Asian J Pharm 7:43–51CrossRefGoogle Scholar
  60. 60.
    Pal D, Nayak A, Hasnain MS (2013) Development and optimization of jackfruit seed starch alginate mucoadhesive beads containing pioglitazone. Curr Drug Deliv 10:608–619CrossRefPubMedGoogle Scholar
  61. 61.
    Nayak AK, Pal D (2015) Chitosan-based interpenetrating polymeric network systems for sustained drug release. In: Tiwari A, Patra HK, Choi J-W (eds) Advanced theranostics materials. Advanced materials book series. Scrivener Publishing LLC, Beverly, pp 207–232Google Scholar
  62. 62.
    Pal D, Nayak A (2011) Development, and optimization of gliclazide loaded alginate–methyl cellulose mucoadhesive microcapsules. AAPS PharmSciTech 12:1431–1441CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Nayak A, Pal D (2013) Formulation, optimization and evaluation of jackfruit seed starch–alginate mucoadhesive beads of metformin HCl. Int J Biol Macromol 59:264–272CrossRefPubMedGoogle Scholar
  64. 64.
    Nayak A, Pal D, Santra K (2013) Plantago ovata F mucilage–alginate mucoadheisve beads for controlled release of glibenclamide: development, optimization and in vitro–in vivo evaluation. J Pharm 2013:1–11Google Scholar
  65. 65.
    Jana L, Timothy ELD, Jana B, Agata S, Mojca B, Sangram KS, Zofia M, Selestina G, Vanja K, Lucie B (2015) Chitosan hydrogels enriched with polyphenols: antibacterial activity, cell adhesion and growth and mineralization. Carbohydr Polym 129:135–142CrossRefGoogle Scholar
  66. 66.
    Yumiko IM, Yuka U, Yoshinori O, Hiroshi W, Yuki T, Yoshinobu T, Makiya N (2017) Improved sustained release of antigen from immunostimulatory DNA hydrogel by electrostatic interaction with chitosan. Int J Pharm 516:392–400CrossRefGoogle Scholar
  67. 67.
    Chengdong J, Jeffrey S (2012) Sterilization-free chitosan hydrogels for controlled drug release. Mater Lett 72:110–112CrossRefGoogle Scholar
  68. 68.
    Tao W, Liman C, Tingting S, Dayang W (2017) Preparation and properties of a novel thermo-sensitive hydrogel based on chitosan/hydroxypropyl methylcellulose/glycerol. Int J Biol Macromol 93:775–782Google Scholar
  69. 69.
    Valderruten NE, Valverde JD, Zuluaga F, Ruiz-Durantez E (2014) Synthesis and characterization of chitosan hydrogels cross-linked with dicarboxylic acids. React Funct Polym 84:21–28CrossRefGoogle Scholar
  70. 70.
    Bera H, Boddupallia S, Nayak AK (2015) Mucoadhesive-floating zinc–pectinate–sterculia gum interpenetrating polymer network beads encapsulating ziprasidone HCl. Carbohydr Polym 131:108–118CrossRefPubMedGoogle Scholar
  71. 71.
    Jana S, Maji N, Nayak AK, Sen KK, Basu SK (2013) Development of chitosan-based nanoparticles through inter-polymeric complexation for oral drug delivery. Carbohydr Polym 98:870–876CrossRefPubMedGoogle Scholar
  72. 72.
    Jana S, Samanta A, Nayak AK, Sen KK, Jana S (2015) Novel alginate hydrogel core–shell systems for combination delivery of ranitidine HCl and aceclofenac. Int J Biol Macromol 74:85–92CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Dilipkumar Pal
    • 1
    Email author
  • Amit Kumar Nayak
    • 2
  • Supriyo Saha
    • 3
  1. 1.Department of Pharmaceutical SciencesGuru Ghasidas Vishwavidyalaya (A Central University)BilaspurIndia
  2. 2.Department of PharmaceuticsSeemanta Institute of Pharmaceutical SciencesMayurbhanjIndia
  3. 3.Department of Pharmaceutical SciencesSardar Bhagwan Singh PG Institute of Biomedical Sciences and ResearchDehradunIndia

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