Skip to main content
SpringerLink
Log in

Formulation and evaluation of interpenetrating network of xanthan gum and polyvinylpyrrolidone as a hydrophilic matrix for controlled drug delivery system

  • Original Paper
  • Published:
Polymer Bulletin Aims and scope Submit manuscript

Abstract

The prime objective of the present study was to develop novel colon targeting xanthan gum/polyvinylpyrrolidone-co-poly acrylic acid hydrogels for controlled delivery of 5-fluorouracil at colon-specific site by combining the properties of natural and synthetic polymers. Xanthan gum (XG) and polyvinylpyrrolidone (PVP) polymer have been chemically cross-linked with acrylic acid (AA) monomer using ethylene glycol dimethacrylate and ammonium per sulfate/sodium hydrogen sulfite as a cross-linker and initiator, respectively. Different proportions of XG, PVP, acrylic acid and ethylene glycol dimethacrylate were blended with each other to fabricate pH-sensitive hydrogels by free radical polymerization. SEM, FTIR, TGA, DSC, XRD and sol−gel fraction analysis were carried out for characterization and structural analysis of polymeric system. pH-responsive behavior of fabricated hydrogels was investigated by performing swelling studies and in vitro drug release studies at both pH 1.2 and pH 7.4. Toxicity studies were performed on rabbits to evaluate cytotoxicity and biocompatibility. TGA and DSC confirmed that formulations were thermodynamically stable, while FTIR, SEM and XRD revealed the successful grafting of components. By increasing the content of polymer, monomer and cross-linker, gel fraction was found to be increased. Swelling capacity of hydrogels increases with the increase in concentration of monomer, while swelling capacity tends to decreases with the increase in concentration of cross-linker and polymer in hydrogel composition. pH sensitivity of hydrogels was confirmed by swelling dynamic and drug release behavior in simulated gastrointestinal fluids. Toxicity studies confirmed that hydrogels were non-toxic. Drug release kinetics revealed the controlled release pattern of 5-fluorouracil in developed polymeric network. Cross-linked XG/PVP-co-poly (AA) hydrogels can be used as promising candidate for controlled delivery of 5-FU for prolonged treatment period at colon-specific site.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Ganji F, Vasheghani-Farahani E (2009) Hydrogels in controlled drug delivery systems. Iran Polym J 18:63–88

    CAS  Google Scholar 

  2. Ahmed EM (2015) Hydrogel: preparation, characterization, and applications: a review. J Adv Res 6:105–121

    Article  CAS  Google Scholar 

  3. Gupta P, Vermani K, Garg S (2002) Hydrogels: from controlled release to pH-responsive drug delivery. Drug Discov Today 7:569–579

    Article  CAS  Google Scholar 

  4. Hennink WE, van Nostrum CF (2012) Novel crosslinking methods to design hydrogels. Adv Drug Deliv Rev 64:223–236

    Article  Google Scholar 

  5. Peppas N, Bures P, Leobandung W, Ichikawa H (2000) Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm 50:27–46

    Article  CAS  Google Scholar 

  6. Lee SC, Kwon IK, Park K (2013) Hydrogels for delivery of bioactive agents: a historical perspective. Adv Drug Deliv Rev 65:17–20

    Article  CAS  Google Scholar 

  7. Banerjee S, Ray S, Maiti S, Sen KK, Bhattacharyya U, Kaity S, Ghosh A (2010) Interpenetrating polymer network (IPN): a novel biomaterial. Int J Appl Pharm 2:28–34

    Google Scholar 

  8. Lin C-C, Metters AT (2006) Hydrogels in controlled release formulations: network design and mathematical modeling. Adv Drug Deliv Rev 58:1379–1408

    Article  CAS  Google Scholar 

  9. Dragan ES (2014) Design and applications of interpenetrating polymer network hydrogels. A review. Chem Eng J 243:572–590

    Article  CAS  Google Scholar 

  10. Wichterle O, Lim D (1960) Hydrophilic gels for biological use. Nature 185:117

    Article  Google Scholar 

  11. Shalviri A, Liu Q, Abdekhodaie MJ, Wu XY (2010) Novel modified starch–xanthan gum hydrogels for controlled drug delivery: synthesis and characterization. Carbohydr Polym 79:898–907

    Article  CAS  Google Scholar 

  12. Talukdar M, Kinget R (1995) Swelling and drug release behaviour of xanthan gum matrix tablets. Int J Pharm 120:63–72

    Article  CAS  Google Scholar 

  13. Mukhopadhyay P, Sarkar K, Bhattacharya S, Bhattacharyya A, Mishra R, Kundu P (2014) pH sensitive N-succinyl chitosan grafted polyacrylamide hydrogel for oral insulin delivery. Carbohydr polym 112:627–637

    Article  CAS  Google Scholar 

  14. Rizwan M, Peh GS, Ang H-P, Lwin NC, Adnan K, Mehta JS, Tan WS, Yim EK (2017) Sequentially-crosslinked bioactive hydrogels as nano-patterned substrates with customizable stiffness and degradation for corneal tissue engineering applications. Biomaterials 120:139–154

    Article  CAS  Google Scholar 

  15. Roy N, Saha N, Kitano T, Saha P (2012) Biodegradation of PVP–CMC hydrogel film: a useful food packaging material. Carbohydr polym 89:346–353

    Article  CAS  Google Scholar 

  16. Sohail K, Khan IU, Shahzad Y, Hussain T, Ranjha NM (2014) pH-sensitive polyvinylpyrrolidone-acrylic acid hydrogels: impact of material parameters on swelling and drug release. Braz J Pharm Sci 50:173–184

    Article  Google Scholar 

  17. Lee JW, Kim SY, Kim SS, Lee YM, Lee KH, Kim SJ (1999) Synthesis and characteristics of interpenetrating polymer network hydrogel composed of chitosan and poly (acrylic acid). J Appl Polym Sci 73:113–120

    Article  CAS  Google Scholar 

  18. Malana MA, Zafar ZI, Zuhra R (2012) Effect of cross linker concentration on swelling kinetics of a synthesized ternary co-polymer system. J Chem Soc Pak 34:793–801

    CAS  Google Scholar 

  19. Longley DB, Harkin DP, Johnston PG (2003) 5-Fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3:330–338

    Article  CAS  Google Scholar 

  20. Milano G, Roman P, Khater R, Frenay M, Renee N, Namer M (1988) Dose versus pharmacokinetics for predicting tolerance to 5-day continuous infusion of 5-FU. Int J Cancer 41:537–541

    Article  CAS  Google Scholar 

  21. Liu G, Franssen E, Fitch MI, Warner E (1997) Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol 15:110–115

    Article  CAS  Google Scholar 

  22. Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Goodman PJ, Ungerleider JS, Emerson WA, Tormey DC, Glick JH (1990) Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med 322:352–358

    Article  CAS  Google Scholar 

  23. Laftah WA, Hashim S, Ibrahim AN (2011) Polymer hydrogels: a review. Polym Plast Technol 50:1475–1486

    Article  CAS  Google Scholar 

  24. Shoukat H, Pervaiz F, Noreen S, Nawaz M, Qaiser R, Anwar M (2019) Fabrication and evaluation studies of novel polyvinylpyrrolidone and 2-acrylamido-2-methylpropane sulphonic acid-based crosslinked matrices for controlled release of acyclovir. Polym Bull. https://doi.org/10.1007/s00289-019-02837-5

    Article  Google Scholar 

  25. Lii C-Y, Liaw S, Lai V-F, Tomasik P (2002) Xanthan gum–gelatin complexes. Eur Polym J 38:1377–1381

    Article  CAS  Google Scholar 

  26. Hussain T, Ranjha NM, Shahzad Y (2011) Swelling and controlled release of tramadol hydrochloride from a pH-sensitive hydrogel. Des Monomers Polym 14:233–249

    Article  CAS  Google Scholar 

  27. Khalid I, Ahmad M, Minhas M, Barkat K, Sohail M (2018) Cross-linked sodium alginate-g-poly (acrylic acid) structure: a potential hydrogel network for controlled delivery of loxoprofen sodium. Adv Polym Technol 37:985–995

    Article  CAS  Google Scholar 

  28. Lin F-H, Lee Y-H, Jian C-H, Wong J-M, Shieh M-J, Wang C-Y (2002) A study of purified montmorillonite intercalated with 5-fluorouracil as drug carrier. Biomaterials 23:1981–1987

    Article  CAS  Google Scholar 

  29. Zohuriaan M, Shokrolahi F (2004) Thermal studies on natural and modified gums. Polym Test 23:575–579

    Article  CAS  Google Scholar 

  30. Ali AE-H, Shawky H, El Rehim HA, Hegazy E (2003) Synthesis and characterization of PVP/AAc copolymer hydrogel and its applications in the removal of heavy metals from aqueous solution. Eur Polym J 39:2337–2344

    Article  Google Scholar 

  31. Abdelrazek E, Ragab H, Abdelaziz M (2013) Physical characterization of poly (vinyl pyrrolidone) and gelatin blend films doped with magnesium chloride. Plast Polym Technol 2:1–8

    Google Scholar 

  32. Malik NS, Ahmad M, Minhas MU (2017) Cross-linked β-cyclodextrin and carboxymethyl cellulose hydrogels for controlled drug delivery of acyclovir. PLoS ONE. https://doi.org/10.1371/journal.pone.0172727

    Article  PubMed  PubMed Central  Google Scholar 

  33. Yin L, Fei L, Cui F, Tang C, Yin C (2007) Superporous hydrogels containing poly (acrylic acid-co-acrylamide)/O-carboxymethyl chitosan interpenetrating polymer networks. Biomaterials 28:1258–1266

    Article  CAS  Google Scholar 

  34. Ranjha NM, Ayub G, Naseem S, Ansari MT (2010) Preparation and characterization of hybrid pH-sensitive hydrogels of chitosan-co-acrylic acid for controlled release of verapamil. J Mater Sci Mater Med 21:2805–2816

    Article  CAS  Google Scholar 

  35. Shi Y, Liu Z, Yang Y, Xu X, Li Y, Li T (2017) Design of poly (mPEGMA-co-MAA) hydrogel-based mPEG-b-PCL nanoparticles for oral meloxicam delivery. Mater Sci Eng C 76:975–984

    Article  CAS  Google Scholar 

  36. Bueno VB, Bentini R, Catalani LH, Petri DFS (2013) Synthesis and swelling behavior of xanthan-based hydrogels. Carbohydr Polym 92:1091–1099

    Article  CAS  Google Scholar 

  37. Burugapalli K, Bhatia D, Koul V, Choudhary V (2001) Interpenetrating polymer networks based on poly (acrylic acid) and gelatin. I: swelling and thermal behavior. J Appl Polym Sci 82:217–227

    Article  CAS  Google Scholar 

  38. Shah S, Ranjha NM, Javaid Z (2013) Development and evaluation of pH-dependent interpenetrating network of acrylic acid/polyvinyl alcohol. Iran polym J 22:811–820

    Article  CAS  Google Scholar 

  39. Sullad AG, Manjeshwar LS, Aminabhavi TM (2010) Novel pH-sensitive hydrogels prepared from the blends of poly (vinyl alcohol) with acrylic acid-graft-guar gum matrixes for isoniazid delivery. Ind Eng Chem Res 49:7323–7329

    Article  CAS  Google Scholar 

  40. Zarzycki R, Modrzejewska Z, Nawrotek K (2010) Drug release from hydrogel matrices. Ecol Chem Eng S 17:117–136

    CAS  Google Scholar 

  41. Khalid I, Ahmad M, Minhas MU, Barkat K (2018) Synthesis and evaluation of chondroitin sulfate based hydrogels of loxoprofen with adjustable properties as controlled release carriers. Carbohydr polym 181:1169–1179

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacy, Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Bahawalpur, Pakistan

    Maryam Anwar, Fahad Pervaiz, Hina Shoukat, Sobia Noreen, Kanwal Shabbir, Asma Majeed & Saba Ijaz

Authors
  1. Maryam Anwar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fahad Pervaiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hina Shoukat
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sobia Noreen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kanwal Shabbir
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Asma Majeed
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Saba Ijaz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fahad Pervaiz.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Anwar, M., Pervaiz, F., Shoukat, H. et al. Formulation and evaluation of interpenetrating network of xanthan gum and polyvinylpyrrolidone as a hydrophilic matrix for controlled drug delivery system. Polym. Bull. 78, 59–80 (2021). https://doi.org/10.1007/s00289-019-03092-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00289-019-03092-4

Keywords

Search

Navigation