AAPS PharmSciTech

, Volume 15, Issue 6, pp 1476–1489 | Cite as

Synthesis of a Semi-Interpenetrating Polymer Network as a Bioactive Curcumin Film

  • Naeema Mayet
  • Pradeep Kumar
  • Yahya E. Choonara
  • Lomas K. Tomar
  • Charu Tyagi
  • Lisa C. du Toit
  • Viness PillayEmail author
Research Article


This study focused on the synthesis and characterization of a natural polymeric system employing the interpenetrating polymer network (IPN) comprising curcumin as a bioactive. Biopolymers and actives such as chitosan, hypromellose, citric acid, genipin, and curcumin were used to develop an effective, biodegradable, and biocompatible film employed therapeutically as a wound healing platform. The semi-IPN films were investigated for their physicochemical, physicomechanical, and biological properties by quantification by FTIR, DSC, and Young’s modulus. Following characterization, an optimum candidate formulation was produced whereby further in vitro and ex vivo studies were performed. Results revealed a burst release occurring at the first hour with 1.1 mg bioactive released when in contact with the dissolution medium and 2.23 mg due to bioactive permeation through the skin, thus suggesting that the lipophilic nature of skin greatly impacted the bioactive release rate. Furthermore, chemical and mechanical characterization and tensile strength analysis revealed that the degree of crosslinking and concentration of polymeric material used significantly influenced the properties of the film.


biomaterials crosslinker curcumin films semi-interpenetrating polymer network wound healing 



This work was funded by the National Research Foundation (NRF) of South Africa.

Conflict of Interest

The Authors declare that there are no conflicts of interest.


  1. 1.
    Boatang JS, Matthews KH, Stevens HNE, Eccleston GM. Wound healing dressings and drug delivery systems. A review. J Pharm Sci. 2008;97(8):2892–900.CrossRefGoogle Scholar
  2. 2.
    Abdelrahman T, Newton H. Wound dressings: principles and practice. Surgery (oxford). 2011;29:491–5.CrossRefGoogle Scholar
  3. 3.
    Atiyeh BS, Hayek SN, Gunn SW. New technologies for burn wound closure and healing; review of the literature. Burns. 2005;31:944–56.PubMedCrossRefGoogle Scholar
  4. 4.
    Singer AJ, Dagum AB. Current management of acute cutaneous wounds. N Engl J Med. 2008;359:1037–46.PubMedCrossRefGoogle Scholar
  5. 5.
    Tanihara Y, Suzuki Y, Nishmura Y, Suzuki K, Kakimara Y. Thrombin sensitive peptide linkers for biological signal responsive drug release systems. Peptides. 1998;19:421–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Suzuki Y, Tanihara M, Nishmura Y, Suzuki K, Kakimara Y, Shimizu Y. A novel wound dressing with an antibiotic delivery system stimulated by microbial infection. ASA10 J. 1997;43:854–7.Google Scholar
  7. 7.
    Kim HJ, Choi EJ, Oh JS, Lee HC, Park SS, Cho CS. Possibility of wound dressing using poly(L-Leucin)/poly(ethylene glycol)/poly(L-Leucin) triblock copolymer. Biomaterials. 2000;21:131–41.PubMedCrossRefGoogle Scholar
  8. 8.
    Hashimoto T, Suzuki Y, Tanihara M, Kakimara Y, Suzuki K. Development of alginate wound dressings linked with hybrid peptides derived from laminin and elastin. Biomaterials. 2004;25:1407–14.PubMedCrossRefGoogle Scholar
  9. 9.
    Choi YS, Hong SR, Lee YM, Song KW, Park MH, Nam YS. Study on gelatine containing artificial skin. I Preparations and characteristics of novel gelatine-alginate sponge. Biomaterials. 1999;20:409–17.PubMedCrossRefGoogle Scholar
  10. 10.
    Ma L, Gao C, MaO Z, Zhou J, Shen J, Hu X, et al. Collagen/chitosan porous scaffolds with improvised biostability for skin tissue engineering. Biomaterials. 2003;24:4833–41.PubMedCrossRefGoogle Scholar
  11. 11.
    Li X, Chen J, Zhang B, Li M, Diao K, Zhong Z, et al. In-situ injectable nano-composite hydrogel composed of curcumin, N,O-Carboxymethyl chitosan and oxidised alginate for wound healing applications. Int J Pharm. 2012;437:110–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Muzarelli RA, Guerrieri M, Goteri G, Muzarelli C, Armeni T, Ghiselli R, et al. The biocompatibility of dibutyryl chitin in the context of wound dressings. Biomaterials. 2005;26:5844–54.CrossRefGoogle Scholar
  13. 13.
    Kim BS, Gao H, Argum AA, Matyjaszewski K, Hammond P. All star polymer multilayers as pH responsive nanofilms. Macromolecules. 2009;42:368–75.CrossRefGoogle Scholar
  14. 14.
    Crowder ML, Gooding CH. Spiral wound, hollow fibre membrane modules: a new approach to higher mass transfer efficiency. J Membrane Sci. 1997;137:17–29.CrossRefGoogle Scholar
  15. 15.
    Hwang JJ, Stupp SI. Poly(amino acid) bioadhesives for tissue repair. J Biomater Sci Polymer. 2000;11:1023–38.CrossRefGoogle Scholar
  16. 16.
    Dash M, Chiellini F, Ottenbrite RM, Chiellini E. Chitosan—A versatile semi-synthetic polymer in biomedical applications. Prog Polym Sci. 2011;36:981–1014.CrossRefGoogle Scholar
  17. 17.
    Datta HS, Mitra SK, Partwarden B. Wound healing activity of topical application forms based on Ayurvedav. Evid Based Complement Alternat Med. 2011;2011:134378.PubMedCentralPubMedGoogle Scholar
  18. 18.
    Ponnusamy S, Zinjarde S, Bhargava S, Rajamohanan PR, Ravikumar A. Discovering bisdemethoxycurcumin from Curcuma longa rhizome as a potent small molecule inhibitor of human pancreatic a-amylase, a target for type-2 diabetes. Food Chem. 2012;135:2638–42.PubMedCrossRefGoogle Scholar
  19. 19.
    Kurup VP, Barrios CS. Immunomodulatory effects of curcumin in allergy. Mole NutrI and Food Res. 2008;52:1031–9.CrossRefGoogle Scholar
  20. 20.
    Adaramoye OA, Anjos RM, Almeida MM, Veras RC, Silvia DF, Oliviera FA, et al. Hypotensive and endothelium-independent vasorelaxant effects of methanolic extract from Curcuma longa L in rats. J Ethnopharmacol. 2009;124:457–62.PubMedCrossRefGoogle Scholar
  21. 21.
    Dao TT, Nguyen PH, Wonb HK, Kim EH, Park J, Wond BY, et al. Curcuminoids from Curcuma longa and their inhibitory activities on influenza A Neuraminidases. Food Chem. 2012;134(1):21–8.CrossRefGoogle Scholar
  22. 22.
    Sidhu GS, Singh AK, Thaloor D, Banaudha KK, Pathaik GK, Srimal RC, et al. Enhancement of wound healing by curcumin in animals. Wound Repair Regen. 1998;6(2):167–77.PubMedCrossRefGoogle Scholar
  23. 23.
    Mani H, Sidhu GS, Kumari R, Gaddipati JP, Seth P, Maheshwari RK. Curcumin differentially regulates TGF-β1, its receptors and nitric oxide synthase during impaired wound healing. Biofactors. 2002;16:29–43.PubMedCrossRefGoogle Scholar
  24. 24.
    Topham J. Why do some cavity wounds treated with honey or sugar paste heal without scarring. J Wound Care. 2002;11(2):53–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Beppu MM, Vieira RS, Aimoli CG, Santana CC. J Membr Sci. 2007;301:126.CrossRefGoogle Scholar
  26. 26.
    Pauliukaite R, Ghica ME, Fatibello-Filho O, Brett CMA. Anal Chem. 2009;81:5364.PubMedCrossRefGoogle Scholar
  27. 27.
    Singh A, Narvi S, Dutta P, Pandey N. Bull Mater Sci. 2006;29:233.CrossRefGoogle Scholar
  28. 28.
    Machado MO, Lopes ECN, Sousa KS, Airoldi C. Carbohydr Polym. 2009;77:760.CrossRefGoogle Scholar
  29. 29.
    Pujana MA, Perez-Alverez L, Iturbe LCC, Katime I. Biodegradible chitosan nanogels crosslinked with genipin. Carbohydr Polym. 2013;94(2):836–42.CrossRefGoogle Scholar
  30. 30.
    Gao L, Gan H, Meng Z, Gu R, Wu Z, Zhang L, et al. Effects of genipin cross-linking of chitosan hydrogels on cellular adhesion and viability. Colloids Surf B: Biointerfaces. 2014;117:398–405.PubMedCrossRefGoogle Scholar
  31. 31.
    Yan LP, Wang YJ, Ren L, Wu G, Caridade SG, Fan JB, et al. Genipin crosslinked collagen/chitosan biomimetic scaffolds for articular cartilage tissue engineering applications. J Biomed Mater Res Part A. 2010;95A:2.CrossRefGoogle Scholar
  32. 32.
    Huang LLH, Sung HW, Tsai CC, Huang DM. Biocompatibility studies of a biological tissue fixed with a naturally occurring crosslinking reagent. J Biomed Mater Res. 1998;42:568–76.PubMedCrossRefGoogle Scholar
  33. 33.
    Mi FL, Tan YC, Liang HF, Sung HW. In vivo biocompatibility and degradability of a novel injectable-chitosan-based-implant. Biomaterials. 2002;23:181–91.PubMedCrossRefGoogle Scholar
  34. 34.
    Wu W, Liu J, Cao S, Tan H, Li J, Xu F, et al. Drug release behaviour of a pH sensitive semi-interpenetrating polymer network hydrogel composed of poly (vinylalcohol) and star poly (2-dimethyl amino) ethyl mecrylate. Int J Pharm. 2011;416(1):104–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Zhang JT, Huang SW, Zhuo RX. Temperature sensitive polyamidoamine dendrimer/poly (N-isopropyl/acrylamide) hydrogels with improved responsive properties. Macromolecules, Biosc. 2004;4:575–8.CrossRefGoogle Scholar
  36. 36.
    Yao F, Xu LQ, Fu GD, Lin BP. Sliding graft interpenetrating polymer network from simultaneous “click chemistry” and atom transfer radical polymerisation. Macromolecules. 2010;43:9761–70.CrossRefGoogle Scholar
  37. 37.
    Liu YY, Fan XD, Wei BR, Si QF, Chen WX, Sun L. Ph responsive amphillic hydrogel networks with IPN structure: a strategy for controlled drug release. Int J Pharm. 2006;308:205–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Saimani S, Dal-Cin MM, Kumar A, Kingston DM. Separation performance of asymmetric membranes based on PEGDa/PEI semi-interpenetrating polymer network in pure and binary gas mixtures of CO2, N2 and CH2. J Membr Sci. 2010;362:353–9.CrossRefGoogle Scholar
  39. 39.
    Bindu TVL, Vidyavathi M, Kavitha K, Sastry TP, Suresh Kumar RV. Preparation and evaluation of chitosan-gelatin composite films for wound healing activity. Trends Biomater Artif Organs. 2010;24(3):123–30.Google Scholar
  40. 40.
    Kim IY, Yoo MK, Seo JH, Park SS, Na H, Lee HC, et al. Evaluation of semi-interpenetrating polymer networks composed of chitosan and polyxamer for wound dressing applications. Int J Pharm. 2007;341:35–43.PubMedCrossRefGoogle Scholar
  41. 41.
    Shaikh RP, Kumar P, Choonara YE, du Toit LC, Pillay V. Crosslinked electrospun nanofibrous membranes: elucidation of their physicochemical, physicomechanical and molecular disposition. Biofabrication. 2012;4:025002. 21 pp.PubMedCrossRefGoogle Scholar
  42. 42.
    Amnuaikit C, Ikeuchi I, Ogawara K-I, Higaki K, Kimura T. Skin permeation of propranolol from polymeric film containing terpene enhancers for transdermal use. Int J Pharm. 2005;289:167–78.PubMedCrossRefGoogle Scholar
  43. 43.
    Davies DJ, Ward RJ, Heylings JR. Multi-species assessment of electrical resistance as a skin integrity marker for in vitro percutaneous absorption studies. Toxicol in Vitro. 2003;18:351–8.CrossRefGoogle Scholar
  44. 44.
    Sarasam A, Madihally SV. Characterisation of chitosan-polycaprolactone blends for tissue engineering applications. Biomaterials. 2005;26(27):5500–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Zhao QS, Ji QX, Xing K, Li XY, Liu CS, Chen XG. Preparation and characteristics of novel porous hydrogel films based on chitosan and glycerophosphate. Carbohydr Polym. 2009;76:410–6.CrossRefGoogle Scholar
  46. 46.
    Bhuvaneshwari S, Sruthi D, Sivasubramanian V, Niranjana K, Sugunabai J. Development and characterization of chitosan films. Int J Eng Res and Appl (IJERA). 2000;1(2):292–9.Google Scholar
  47. 47.
    Giovino C, Ayensu I, Tetteh J, Boateng JS. Development and characterisation of chitosan films impregnated with insulin loaded PEG-b-PLA nanoparticles (NPs): a potential approach for buccal delivery of macromolecules. Int J Pharm. 2012;428:143–51.PubMedCrossRefGoogle Scholar
  48. 48.
    Boatang JS, Pawar HV, Tetteh J. Polyox and carrageenan based composite film dressing containing anti-microbial and anti-inflammatory drugs for effective wound healing. Int J Pharm. 2013;441(1–2):181–91.CrossRefGoogle Scholar
  49. 49.
    Sung JH, Hwang MR, Kim JO, Lee JH, Kim YI, Kim JH, et al. Gel characterisation and in vivo evaluation of minocycline-loaded wound dressing with enhanced wound healing using polyvinyl alcohol and chitosan. Int J Pharm. 2010;392:232–40.PubMedCrossRefGoogle Scholar
  50. 50.
    Queen D, Gaylor JDS, Evans JH, Courtney JM, Reid WH. The preclinical evaluation of the water vapour transmission rate through burn wound dressings. Biomaterials. 1987;8:367–71.PubMedCrossRefGoogle Scholar
  51. 51.
    Pakravan MP, Heuzey MC, Ajji A. A fundamental study of Chitosan/PEO electrospinning. Polymer. 2011;52:4813–24.CrossRefGoogle Scholar
  52. 52.
    Barnes HA, Walter K. The yield stress myth? Rheol Acta. 1985;24:323–6.CrossRefGoogle Scholar
  53. 53.
    Pawar HV, Tetteh J, Boateng JS. Preparation, optimisation and characterisation of novel wound healing film dressings loaded with streptomycin and diclofenac. Colloids Surf B: Biointerfaces. 2013;102:102–10.PubMedCrossRefGoogle Scholar
  54. 54.
    Zhao YS, Lu CT, Zhang Y, Xiao J, Zhao YP, Tian JL, et al. Selection of high efficient transdermal lipid vesicle for curcumin skin delivery. Int J Pharm. 2013;454:302–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Scheuplein RJ. Permeability of the skin. Handbook of physiology, Reactions to environmental agents. 2011; doi:  10.1002/cphy.cp090119.
  56. 56.
    Seetharaman S, Natesan S, Stowers RS, Mullens C, Baer DG, Suggs LG, et al. A PEGylated fibrin-based wound dressing with antimicrobial and angiogenic activity. Acta Biomater. 2011;7:2787–96.PubMedCrossRefGoogle Scholar
  57. 57.
    Rana V, Babita K, Goyal D, Tiwary AK. Soduim citrate crosslinked chitosan films: optimisation and substitute for human/rat/rabbit epidermal sheets. J Pharm Pharmaceut Sci. 2005;8(1):10–7.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2014

Authors and Affiliations

  • Naeema Mayet
    • 1
  • Pradeep Kumar
    • 1
  • Yahya E. Choonara
    • 1
  • Lomas K. Tomar
    • 1
  • Charu Tyagi
    • 1
  • Lisa C. du Toit
    • 1
  • Viness Pillay
    • 1
    Email author
  1. 1.Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa

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