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. 2007 May 24;8(2):E94–E101. doi: 10.1208/pt0802039

Chitosan film containing fucoidan as a wound dressing for dermal burn healing: Preparation and in vitro/in vivo evaluation

Ali Demir Sezer 1,, Fatih Hatipoglu 2, Erdal Cevher 3, Zeki Oğurtan 4, Ahmet Levent Bas 5, Jülide Akbuğa 1
PMCID: PMC2750378  PMID: 17622117

Abstract

The aim of this study was to develop chitosan film containing fucoidan and to investigate its suitability for the treatment of dermal burns on rabbits. Porous films, thickness between 29.7 and 269.0 μm, were obtained by the solvent dropping method. Water vapor permeability (3.3–16.6/0.1 g), the swelling (0.67–1.77 g/g), tensile strength (7.1–45.8 N), and bioadhesion (0.076–1.771 mJ/cm2) of the films were determined. The thinnest films were obtained with the lowest chitosan concentration (P<.05). The water absorption capacity of the films sharply increased with the freeze-drying technique. The film having the thickness of 29.7 μm showed the highest amount of moisture permeability (16.6 g/0.1 g). Higher chitosan concentration significantly increased tensile strength of the films (P<.05). Using higher concentration of lactic acid made films more elastic and applicable, and these films were selected for in vivo studies. Seven adult male New Zealand white rabbits were used for the evaluation of the films on superficial dermal burns. Biopsy samples were taken at 7, 14, and 21 days after wounding, and each wound site was examined macroscopically and histopathologically. After 7 days treatment, fibroplasia and scar were observed on wounds treated with fucoidan-chitosan film. The best regenerated dermal papillary formation, best reepithelization, and the fastest closure of wounds were found in the fucoidan-chitosan film treatment group after 14 days compared with other treatment and control groups. It can be concluded that fucoidan-chitosan films might be a potential treatment system for dermal burns and that changing formulation variables can modulate the characterizations of the films.

Keywords: Fucoidan, chitosan, biopolymer, film, wound healing

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References

  • 1.Park JE, Barbul A. Understanding the role of immune regulation in wound healing. Am J Surg. 2004;187:S11–S16. doi: 10.1016/S0002-9610(03)00296-4. [DOI] [PubMed] [Google Scholar]
  • 2.Shakespeare P. Burn wound healing and skin substitutes. Burns. 2001;27:517–522. doi: 10.1016/S0305-4179(01)00017-1. [DOI] [PubMed] [Google Scholar]
  • 3.Lloyd LL, Kennedy JF, Methacanon P, Paterson M, Knill CJ. Carbohydrate polymers as wound management aids. Carbohydr Polym. 1998;37:315–322. doi: 10.1016/S0144-8617(98)00077-0. [DOI] [Google Scholar]
  • 4.Alemdaroğlu C, Değim Z, Çelebi N, Zor F, Öztürk S, Erdoğan D. An investigation on burn wound healing in rats with chitosan gel formulation containing epidermal growth factor. Burns. 2006;32:319–327. doi: 10.1016/j.burns.2005.10.015. [DOI] [PubMed] [Google Scholar]
  • 5.Ueno H, Murakami M, Okumura M, Kadosawa T, Uede T, Fujinaga T. Chitosan accelerates the production of osteopontin from polymorphonuclear leukocytes. Biomaterials. 2001;22:1667–1673. doi: 10.1016/S0142-9612(00)00328-8. [DOI] [PubMed] [Google Scholar]
  • 6.Pereira M, Mulloy B, Mourao PAS. Structure and anticoagulant activity of sulfated fucans. J Biol Chem. 1999;274:7656–7667. doi: 10.1074/jbc.274.12.7656. [DOI] [PubMed] [Google Scholar]
  • 7.Fujimura T, Shibuya Y, Moriwaki S, et al. Fucoidan is the active component of fucus vesiculosus that promotes contraction of fibroblast-populated collagen gels. Biol Pharm Bull. 2000;23:1180–1184. doi: 10.1248/bpb.23.1180. [DOI] [PubMed] [Google Scholar]
  • 8.O'Leary R, Rerek M, Wood EJ. Fucoidan modulates the effect of transforming growth factor (TGF)-β1 on fibroblast proliferation and wound repopulation in in vitro models of dermal wound repair. Biol Pharm Bull. 2004;27:266–270. doi: 10.1248/bpb.27.266. [DOI] [PubMed] [Google Scholar]
  • 9.Sezer AD, Cevher E, Akbuğa J. In vitro characterization of chitosan films containing fucoidan. Paper presented at: 12th International Pharmaceutical Technology Symposium; September 13–15, 2004; Istanbul, Turkey.
  • 10.Remuñán-López C, Bodmeier R. Mechanical water uptake and permeability of crosslinked chitosan glutamate and alginate films. J Control Release. 1997;44:215–225. doi: 10.1016/S0168-3659(96)01525-8. [DOI] [Google Scholar]
  • 11.Shu XZ, Zhu KJ, Weihong S. Novel pH-sensitive citrate cross-linked chitosan film for drug controlled release. Int J Pharm. 2001;212:19–28. doi: 10.1016/S0378-5173(00)00582-2. [DOI] [PubMed] [Google Scholar]
  • 12.Kalapathy U, Proctor A, Shultz J. Production and properties of flexible sodium silicate films from rice hull ash silica. Bioresour Technol. 2000;72:99–106. doi: 10.1016/S0960-8524(99)00112-1. [DOI] [PubMed] [Google Scholar]
  • 13.Wong CF, Yuen KH, Peh KK. Formulation and evaluation of controlled release Eudragit buccal patches. Int J Pharm. 1999;178:11–22. doi: 10.1016/S0378-5173(98)00342-1. [DOI] [PubMed] [Google Scholar]
  • 14.Knabl JS, Bauer W, Andel H, et al. Progression of burn wound depth by systemical application of a vasoconstrictor: an experimental study with a new rabbit model. Burns. 1999;25:715–721. doi: 10.1016/S0305-4179(99)00086-8. [DOI] [PubMed] [Google Scholar]
  • 15.Derenzini M. The AgNORs. Micron. 2000;31:117–120. doi: 10.1016/S0968-4328(99)00067-0. [DOI] [PubMed] [Google Scholar]
  • 16.Trere D. AgNOR staining and quantification. Micron. 2000;31:127–131. doi: 10.1016/S0968-4328(99)00069-4. [DOI] [PubMed] [Google Scholar]
  • 17.Berthod F, Saintigny G, Chretien F, Hayek D, Collombel C, Damour O. Optimization of thickness, pore size and mechanical properties of a biomaterial designed for deep burn coverage. Clin Mater. 1994;15:259–265. doi: 10.1016/0267-6605(94)90055-8. [DOI] [PubMed] [Google Scholar]
  • 18.Khan T, Peh K, Ch'ng H. Mechanical, bioadhesive strength and biological evaluations of chitosan films for wound dressing. J Pharm Pharm Sci. 2000;3:303–311. [PubMed] [Google Scholar]
  • 19.Bangyekan C, Duangdao AO, Srikulkit K. Preparation and properties evaluation of chitosan-coated cassava starch films. Carbohydr Polym. 2006;63:61–71. doi: 10.1016/j.carbpol.2005.07.032. [DOI] [Google Scholar]
  • 20.Henriksen I, Green KL, Smart JD, Smistad G, Karlsen J. Bioadhesion of hydrated chitosans: an in vitro and in vivo study. Int J Pharm. 1996;145:231–240. doi: 10.1016/S0378-5173(96)04776-X. [DOI] [Google Scholar]
  • 21.Ishihara M, Nakanishia K, Ono K, et al. Photocrosslinkable chitosan as a dressing for wound occlusion and accelerator in healing process. Biomaterials. 2002;23:833–840. doi: 10.1016/S0142-9612(01)00189-2. [DOI] [PubMed] [Google Scholar]
  • 22.Smart JD. The basics and underlying mechanisms of mucoadhesion. Adv Drug Deliv Rev. 2005;57:1556–1568. doi: 10.1016/j.addr.2005.07.001. [DOI] [PubMed] [Google Scholar]
  • 23.Ueno H, Mori T, Fujinaga T. Topical formulation and wound healing applications of chitosan. Adv Drug Deliv Rev. 2001;52:105–115. doi: 10.1016/S0169-409X(01)00189-2. [DOI] [PubMed] [Google Scholar]
  • 24.Hideyuki S, Masato N, Toshiko K, Haruji S, Hidesuke H, Terou Y, inventors. Complex of fibroblast growth factor. Japan Patent (JP) application no.: JP/1996/10017498. January 20, 1998.
  • 25.Provenzano PP, Alejandro-Osorio AL, Valhmu WB, Jensen KT, Vanderby R. Intrinsic fibroblast-mediated remodeling of damaged collagenous matrices in vivo. Matrix Biol. 2005;23:543–555. doi: 10.1016/j.matbio.2004.09.008. [DOI] [PubMed] [Google Scholar]
  • 26.Eichler MJ, Carlson MA. Modeling dermal granulation tissue with the linear fibroblast-populated collagen matrix: a comparison with the round matrix model. J Dermatol Sci. 2006;41:97–108. doi: 10.1016/j.jdermsci.2005.09.002. [DOI] [PubMed] [Google Scholar]
  • 27.Erdağ G, Sheridan RL. Fibroblasts improve performance of cultured composite skin substitutes on athymic mice. Burns. 2004;30:322–328. doi: 10.1016/j.burns.2003.12.007. [DOI] [PubMed] [Google Scholar]

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