Review
Antimicrobial properties of chitosan and mode of action: A state of the art review

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Abstract

Owing to its high biodegradability, and nontoxicity and antimicrobial properties, chitosan is widely-used as an antimicrobial agent either alone or blended with other natural polymers. To broaden chitosan's antimicrobial applicability, comprehensive knowledge of its activity is necessary. The paper reviews the current trend of investigation on antimicrobial activities of chitosan and its mode of action. Chitosan-mediated inhibition is affected by several factors can be classified into four types as intrinsic, environmental, microorganism and physical state, according to their respective roles. In this review, different physical states are comparatively discussed. Mode of antimicrobial action is discussed in parts of the active compound (chitosan) and the target (microorganisms) collectively and independently in same complex. Finally, the general antimicrobial applications of chitosan and perspectives about future studies in this field are considered.

Introduction

Chitosan [poly-(b-1/4)-2-amino-2-deoxy-D-glucopyranose] is a collective name for a group of partially and fully deacetylated chitin compounds (Tikhonov et al., 2006). Due to its unique biological characteristics, including biodegradability and nontoxicity, many applications have been found either alone or blended with other natural polymers (starch, gelatin, alginates) in the food, pharmaceutical, textile, agriculture, water treatment and cosmetics industries (Arvanitoyannis et al., 1998, Arvanitoyannis, 1999, Haque et al., 2005, Kim et al., 2005, Roberts, 1992, Yamada et al., 2005). Antimicrobial activity of chitosan has been demonstrated against many bacteria, filamentous fungi and yeasts (Hirano and Nagao, 1989, Kendra and Hadwiser, 1984, Uchida et al., 1989, Ueno et al., 1997). Chitosan has wide spectrum of activity and high killing rate against Gram-positive and Gram-negative bacteria, but lower toxicity toward mammalian cells (Franklin and Snow, 1981, Takemono et al., 1989). Ever since the broad-spectrum antibacterial activity of chitosan was first proposed by Allen (Allan and Hardwiger, 1979), along with great commercial potential, the antimicrobial property of chitosan and its derivatives have been attracting great attention from researchers.

Investigation of the antimicrobial properties of chitosan has been a long journey of scientific exploration and technological development. The journey began two decades ago, with studies on the biological phenomena arising from foodborne and soilborne pathogenic fungi in the food and agriculture industries (Rabea et al., 2003). In light of their intimate relationship with human activities, bacteria rightly began to receive more attention in the search for efficacious antimicrobials. The studies at that time were typically carried out via chemical, biochemical, microbiological and medical assays of chitosan and its derivatives. In some cases, but rarely so, molecular and cell approaches were utilized. The outcomes obtained through this period suggested that antimicrobial activities of chitosan and its derivatives relied on numerous intrinsic and extrinsic factors, such as pH, microorganism species, presence or absence of metal cations, pKa, Molecular weight (Mw) and degree of deacetylation (DD) of chitosan, etc. Some basic hypotheses about underlying antimicrobial mechanisms were also proposed (Zivanovic et al., 2004). Based on the outcomes, various antimicrobial agents based on chitosan or its derivatives emerged. At the same time, since biocide resistant bacteria and fungi, growing public health awareness of pathogenic microorganism raised demands for safe and efficacious agents that were less prone to stimulating development of resistance. In addition to tremendous advancements in molecular biological, pharmaceutical, cell biological technologies and detecting methods, nanotechnology emerged and began playing an extraordinary role, carrying the potential to extend antimicrobial treatment to the atomic level.

The many approaches that have been used in studying antimicrobial activities of chitosan and its derivatives have given rise to various physical forms of chitosan in differing methods, from the original solution applied in agriculture, to film structure in food sector and to ubiquitous pharmaceutical nanostructure materials. Different physical states of chitosan, as a crucial factor influencing antimicrobial activity, are supposed to have strongly considered but always being underestimated. Chitosan's water-solubility casts important impact on its particular antimicrobial activities, and the relevant researches have accordingly attracted understandable attention in the water solution. In contrast, solid state research has been confining to the application of antimicrobial properties such as beads, films, fibers, and hydrogels, mostly aimed at biomedical applications (Kong et al., 2008a). Little attention has been paid to systemic investigations of the inhibitory effect in solid state, needless to its mode of action.

Based on the current situation of research and progress in corresponding areas, this review attempts to sum up the general developments in the study of antimicrobial properties of chitosan. Comparison of the antimicrobial activity between different physical states of chitosan is made, especially the solid form. Differences among influencing factors and corresponding modes of action are discussed in detail. Finally, present and potential future applications are discussed.

Section snippets

Investigation on antimicrobial activity of chitosan and its derivatives

Variations in chitosan's bactericidal efficacy arise from various factors. According to roles playing, these factors can be classified into four categories as follow: (1) microbial factors, related to microorganism species and cell age; (2) intrinsic factors of chitosan, including positive charge density, Mw, concentration, hydrophilic/hydrophobic characteristic and chelating capacity; (3) physical state, namely water-soluble and solid state of chitosan; (4) environmental factors, involving

Mode of antibacterial action

The exact mechanisms of the antibacterial activities of chitosan and its derivatives are still unknown. It is known that chitosan's antimicrobial activity is influenced by a number of factors that act in and orderly and independent fashion. The mode of antibacterial action is discussed in part of chitosan and microorganism below.

Antimicrobial application of chitosan and its derivatives

The ideal antimicrobial polymer should possess the following characteristics: (1) easily and inexpensively synthesized, (2) stable in long-term usage and storage at the temperature of its intended application, (3) not soluble in water for a water-disinfection application, (4) does not decompose to and/or emit toxic products, (5) should not be toxic or irritating to those who are handling it, (6) can be regenerated upon loss of activity, and (7) biocidal to a broad spectrum of pathogenic

Perspectives and future

Over the last decades, considerable interest and attention have been focused on chitosan ascribing from its potential and advantages as antimicrobial agent. Investigations on its antimicrobial property originated from conventional morphology observation to micron and submicron inner structural metabolism study. The methods and technologies used to evaluate the phenomena and results have gone beyond sole biological conception, but yet incorporate a combination of disciplines involving chemistry,

Acknowledgments

This work was supported by grants from NSFC (30770582), ISTCP (2006DFA33150) and the Shandong Science Foundation (Y2006C110), P. R. China.

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