International Journal of Biological Macromolecules 45 (2009) 16–21 Contents lists available at ScienceDirect International Journal of Biological Macromolecules journal homepage: www.elsevier.com/locate/ijbiomac Chitosan topical gel formulation in the management of burn wounds Ibrahim A. Alsarra ∗ Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia article info Article history: Received 25 February 2009 Received in revised form 24 March 2009 Accepted 25 March 2009 Available online 2 April 2009 Keywords: Chitosan Wound healing Histophathological studies Fucidin ® Topical applications abstract Wound healing properties of chitosan with different molecular weight and degree of deacetylation ranges have been examined. The macroscopic image and histopathology were examined using chitosan, Fucidin ® ointment and to blank. The rate of contraction was evaluated by determination of the unclosed area as a function of time. The treated wounds were found to contract at the highest rate with high molecu- lar weight–high degree of deacetylation chitosan-treated rats as compared to untreated, treated, and Fucidin ® ointment-treated rats. Wounds treated with high molecular weight chitosan had significantly more epithelial tissue (p < 0.05) than wounds with any other treatment and the best re-epithelization and fastest wounds closure were found with the high molecular weight chitosan treatment group. His- tological examination and collagenase activity studies revealed advanced granulation tissue formation and epithelialization in wounds treated with high molecular weight chitosan (p < 0.05). High molecular weight with high degree of deacetylation chitosan samples therefore demonstrates potential for use as a treatment system for dermal burns. © 2009 Elsevier B.V. All rights reserved. 1. Introduction Slow healing and non-healing wounds, such as ulcers, as well as wounds caused by major or minor injuries, surgery, or burns, represents the most widespread treatable conditions encountered by humans and animals. Wound repair is a well highly coordinated process that involves a series of overlapping phases: inflammation, cell proliferation, matrix deposition and tissue remodeling. Under- lying repair is a complex dynamic series of events including clotting, inflammation, granulation tissue formation, epithelialization, neo- vascularization, collagen synthesis, and wound contraction [1]. Briefly, the wound healing process consists of three major stages. First, inflammatory cells from the surrounding tissue move towards the lesion site. Subsequently, fibroblasts appear and begin to pro- duce collagen connective fibers that impart tensile strength to the regenerating tissue. Simultaneously, numerous capillaries begin to form to supply the site with nutrients and oxygen, while the epithe- lial cells at the edge of the wound start filing in the area under the scab. In the third and final phase, the new epithelium forms and the wound is considered healed [2]. Chitosan is obtained by partial deacetylation of the amines of chitin, which yields a copolymer of N-acetyl-glucosamine and N-glucosamine. Its use has been explored in various biomaterial and medical applications. Chitosan has desirable qualities, such as hemostasis, wound healing, bacteriostatic, biocompatibility, and ∗ Tel.: +966 1 4677504; fax: +966 1 4676295. E-mail address: ialsarra@ksu.edu.sa. biodegradability properties [3,4]. Chitosan appears to have no adverse effects after implantation in tissues and, for this reason, it has been used for a wide range of biomedical applications [5]. Chitosan may be used to inhibit fibroplasia in wound healing and to promote tissue growth and differentiation in culture [6]. It is commonly accepted that the ideal wound covering should mimic many properties of human skin. It should be adhesive, elas- tic, durable, occlusive and impermeable to bacteria [7]. Because of their biocompatibility, ability to absorb exudates, and film form- ing properties, chitosan products are good candidates for burn and wound management [8]. The main parameters influencing the characteristics of chitosan are its molecular weight (MW) and its degree of deacetylation (DD) [9]. Due to the diversity of the sources of chitosan, and to the fact that it is commercially available with a wide range of DD and MW, each of which may have an effect on chitosan properties, it is impor- tant to take into consideration the effects of these parameters on biomedical activity in order to optimize the desired application. The molecular weight of chitosan is likely to be the more impor- tant property because a minimum molecular weight is often needed to achieve the desired property [10]. Several researchers have found that the acceleration of wound healing by chitosan is related to its chemical structure, whereas other reports indicated that the wound repair effect is related to the different physical forms of the chitosan samples used [11–13]. This discrepancy appears to result, at least in part, from the different chemical compositions and physical forms of the biopolymer samples investigated, making it difficult to dif- ferentiate the relationship between chitosan structure and its effect on the wound healing process. 0141-8130/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.ijbiomac.2009.03.010