A STUDY OF BIODEGRADABLE POLYMERS AND THEIR APPLICATIONS WITH SPECIAL FOCUS ON CHITIN POLYMERSSELF STUDY PROJECT

4/25/2012Self Study project

JIGYASU JUNEJA KSHITIJ SINGH MEHAK JAIN RISHAB JAIN2K10/PS/017 2K10/PS/020 2K10/PS/025 2K10/PS/037

CONTENTS BIODEGRADABLE POLYMERS AS BIOMATERIALS Polysaccharides STARCH CHITIN AND CHITOSAN PRODUCTION OF CHITIN FIBRES CHITOSAN CHEMISTRY OF CHITIN AND CHITOSAN PROPERTIES OF CHITIN AND CHITOSAN APPLICATIONS OF CHITIN AND CHITOSAN CONCLUSION REFERENCES

Biodegradable polymers as biomaterials

A biomaterial can be defined as a material intended to interface with biological systems to evaluate, treat, augment or replace any tissue, organ or function of the body [5]. Theessential prerequisite to qualify a material as a biomaterial is biocompatibility, which is the ability of a material to perform with an appropriate host response in a specific application. The tissue response to an implant depends on a myriad of factors ranging from the chemical, physical and biological properties of the materials to the shapeand structure of the implant.

Some of the important properties of a biodegradable biomaterial can be summarized as follows:

• The material should not evoke a sustained inflammatory or toxic response upon implantation in the body.

• The material should have acceptable shelf life.

• The degradation time of the material should match the healing or regeneration process.

• The material should have appropriate mechanical properties for the indicated application and the variation in mechanical properties with degradation should be compatible with the healing or regeneration process.

• The degradation products should be non-toxic, and able to get metabolized and cleared from the body.

• The material should have appropriate permeability and processibility for the intended application

Both synthetic polymers and biologically derived (or natural) polymers have been extensively investigated as biodegradable polymeric biomaterials. Biodegradation of polymeric biomaterials involves cleavage of hydrolytically or enzymaticaly sensitive bonds in the polymer leading to polymer erosion.

Depending on the mode of degradation, polymeric biomaterials can be further classified into hydrolytically degradable polymers and enzymatically degradable polymers. Most of the naturally occurring polymers undergo enzymatic degradation.

Natural polymers can be considered as the first biodegradable biomaterials used clinically. Chemical modification of these polymers also can significantly affect their rate of degradation. Natural polymers possess several inherent advantages such as bioactivity, the ability to present receptor-binding ligands to cells, susceptibility to cell-triggered proteolytic degradation and natural remodeling. The inherent bioactivity of these natural polymers has its own downsides.

Hydrolytically degradable polymers as biomaterialsHydrolytically degradable polymers are polymers that have hydrolytically labile chemical bonds in their back bone. The functional groups susceptible to hydrolysis include esters, orthoesters, anhydrides, carbonates, amides, urethanes, ureas, etc. Two general routes are used to develop hydrolytically sensitive polymers for biomedical applications. They are step (condensation) polymerization and addition (chain) polymerization including ringopening polymerization. Step process is used to prepare a variety of hydrolytically sensitive polymer classes, such as polyanhydrides, poly(ortho esters) and polyurethanes. Ring

opening polymerization (ROP) is an extensively investigated polymerization route to develop hydrolytically sensitive polymers, including the poly(a-esters) and polyphosphazenes.

Poly(alpha-esters)

Poly(alpha-ester)s are thermoplastic polymers with hydrolytically labile aliphatic ester linkages in their backbone. Although all polyesters are theoretically degradable as esterification is a chemically reversible process, only aliphatic polyesters with reasonably short aliphatic chains between ester bonds can degrade over the time frame required for most of the biomedical applications.

The most extensively studied monomers for aliphatic polyester synthesis for biomedical applications are lactide, glycolide and caprolactone. Non-woven polyglycolide fabrics have been extensively used as scaffolding matrices for tissue regeneration due to its excellent degradability, good initial mechanical properties and cell viability sutures and its ability to help regenerate biological tissue.

Enzymatically degradable polymers as biomaterials

Proteins and Poly (amino acids)Proteins, the major structural components of many tissues are essentially amino acid polymers arranged in a three-dimensional folded structure and are one of the most important classes of biomolecules identified. Being a major component of the natural tissues, proteins and other amino acid-derived polymers have been a preferred biomaterial for sutures, haemostatic agents, scaffolds for tissue engineering and drug delivery vehicles. Furthermore, protein based biomaterials are known to undergo naturally-controlled degradation processes.

Natural poly(amino acids)

Natural poly(amino acids) are biodegradable ionic polymers that differ from proteins in certain aspects. Natural poly (amino acids), such as cyanophycin, poly (e-L-lysine) and poly-g-glutamic acid are mainly composed of one type of amino acid. These molecules exhibit polydispersity and in addition to alpha-amide linkages, they exhibit other types of amide linkages that involve beta- and gamma-carboxylic groups as well as e-amino groups.

Poly-g-glutamic acid (g-PGA) is an anionic, water-soluble biodegradable homo-polyamide produced by microbial fermentation and is composed of D- and L-glutamic acid units connected by amide linkages between a-amino and g-carboxylic acid groups. This biodegradable polymer was first isolated in 1937 by autoclaving capsules of Bacillus anthracis.

Several modified forms of g-PGA have been developed so far as drug delivery vehicles, tissue engineering scaffolds and as thermosensitive polymers. The high functionality of g-PGA makes it a promising material for developing bioactive scaffolds for tissue engineering application.

PolysaccharidesPolysaccharides are macromolecules formed from many monosaccharide units joined together by glycosidic linkages. Polysaccharides are gaining renewed interest as biomaterials due to the growing body of literature pointing to their unique biological functions ranging from cell signaling to immune recognition. This combined with new synthetic routes currently available to modify polysaccharides or synthesize oligosaccharide moieties, biodegradability and ability to fabricate appropriate structures, make them one of the most important and extensively investigated natural biomaterials.

Polysaccharides of human origin Hyaluronic acid (HA) was first isolated in 1934 from the vitreous humor of the eye by Meyer and Palmer. This biopolymer has steadily raised interest as a unique biomaterial since its discovery.

Since HA is produced by cells during early wound healing, this polymer has been extensively investigated for wound dressing applications.

Structure of HA

Polysaccharides of non-human originIn addition to the glycosaminoglycans present in the human body, other types of polysaccharide molecules have also raised interest as biodegradable polymeric biomaterials. The most important members among this class are the cationic polymer chitosan, which originates from crustacean skeletons, and the anionic polymer alginic acid, derived from brown algae, both of which have been used as drug delivery vehicles .One of the most extensively investigated polyelectrolyte complexes for biomedical applications involve chitosan and alginic acid. They are used as wound dressings and as drug as well as cell delivery vehicles.

STARCH

Starch is a natural biopolymer consisting predominantly of two polymer types of glucose namely amylose and

amylopectin. The alpha linkage of amylose starch allows it to be flexible and digestible.

Structure of amylose Structure of amylopectin

The advantages of starch for plastic production include its renewability, good oxygen barrier in the dry state,

abundance, low cost and biodegradability. The longstanding quest of developing starch-based biodegradable

plastics has witnessed the use of different starches in many forms such as native granular starch, modified starch,

plasticized starch and in blends with many synthetic polymers, both biodegradable and non-biodegradable, for

the purpose of achieving cost effectiveness and biodegradation respectively. The type of starch and synthetic

polymer as well as their relative proportions in the blends influence the properties of the resulting plastic

blends. Starch has been used as fillers in starch-filled polymer blends, thermoplastic starch (TPS) (produced from

the combination of starch, plasticizer and thermomechanical energy), in the production of foamed starch and

biodegradable synthetic polymer like polylactic acid (PLA) with varying results. Starch is typically plasticized,

destructured, and/or blended with other materials to form useful mechanical properties.

Experimental studies have demonstrated that cassava starch could be used for making various types of packaging products. As a major source of starch in tropical and subtropical regions, cassava is a promising raw material for the development of biodegradable plastics in these areas. Biodegradability of Starch Based Polymer Starch is a linear polymer (polysaccharide) made up of repeating glucose groups linked by glucosidic linkages in the 1-4 carbon positions. Starch-based biodegradable plastics may have starch contents ranging from 10% to greater than 90%. Starch based polymers can be based on crops such as corn (maize), wheat, cassava or potatoes.

At lower starch contents (less than 60%) the starch particles act as weak links in the plastic matrix and are sites for biological attack. This allows the polymer matrix to disintegrate into small fragments, but not for the entire polymer structure to actually bio-degrade. Biodegradation of starch based polymers is a result of enzymatic attack at the glucosidic linkages between the sugar groups leading to a reduction in chain length and the splitting off of sugar units (monosaccharides, disaccharides and oligosaccharides) that are readily utilized in biochemical pathways. High starch content plastics are highly hydrophilic and readily disintegrate on contact with water. This can be overcome through blending, as the starch has free hydroxyl groups which readily undergo a number of reactions such as acetylation, esterification and etherification. There are several categories of biodegradable starch-based polymers including: Thermoplastic starch products; Starch synthetic aliphatic polyester blends; Starch PBS/PBSA polyester blends; and Starch PVOH Blends.

Chitin and chitosanChitin and chitosan are natural polymers extracted from various plants and animals. In recent years, these two polymers have attracted much interest because of their biodegradability, biocompatibility, wound-healing acceleration and many other unique properties. As a natural renewable resource, they offer many potential applications in a number of diversified fields. Chitin and chitosan fibers have been found useful as a biomaterial for potential applications such as sutures and wound dressings.

Chitin, poly-(1,4)-2-acetamido-2-deoxy-b-D-glucose (Fig. (a)), is the second most abundant natural polymer. Chitosan is the deacetylated product of chitin, i.e. poly-(1,4)-2-amino-2-deoxy-b-D-glucose (Fig. (b)). both polymers exist widely in many species of fungi and in the cuticular or exoskeletons of crusteceans and insects.

CHITIN (natural aminopolysaccharide)

IntroductionIt is a long-chain polymer of a N -acetylglucosamine , a derivative of glucose, and is found in many places throughout the natural world. It is the main component of the cell walls of fungi, the exoskeletons of arthropods such as crustaceans (e.g., crabs, lobsters and shrimps) and insects, the radulas of mollusks, and the beaks of cephalopods, including squid and octopi In terms of structure, chitin may be compared to the polysaccharide cellulose and, in terms of function, to the protein keratin

Chitin fibers stand apart from all the other biodegradable natural fibers in many inherent properties such as biocompatibility, non-toxicity, biodegradability, low immunogenicity, non-toxicity, etc.The positive attributes of excellent biocompatibility and admirable biodegradability with ecological safety and low toxicity with versatile biological activities such as antimicrobial activity and low immunogenicity have provided ample opportunities for its further development.

Sources And Processing of chitin

‘Chiton’, meaning tunic or ‘coat of mail’, which depicts the fact that chitin was first identified from exoskeletons of fungi, shells and bones. Like cellulose in plants, chitin acts as a reinforcement material for cell walls in lower animals and plants whose foods are rich in nitrogen. Chitin exists widely in cell walls of fungi, molds and yeasts, and in the cuticular and exoskeletons of invertebrates, such as crabs, shrimps and insects. Commercially chitin is mainly produced from shell wastes of crabs, shrimps and krills, which are generated by seafood industries. The shell wastes are typically composed of three components: proteins, minerals and chitin.

The processing of crustacean shells mainly involves the removal of proteins and the disso-lution of calcium carbonate which is present in crab shells in high concentrations. The resulting chitin is deacetylated in 40% sodium hydroxide at 1208C for 1–3 h. This treatment produces 70% deacetylated chitosan. During the commercial extraction process, the shells are first cleaned and broken down to flakes, which are then treated with a dilute acidic solution to remove the minerals, typically calcium carbonate. After washing, the shells are treated with a dilute alkali solution at a slightly elevated temperature to remove the protein. This process is then repeated until a purified chitin is produced. A bleaching process is often involved to remove the pigment.

Chitin Solvents

As has just been pointed out, in order to spin the chitin fibers, it is essential that a stable chitin solution is formed. Because of the relatively inert chemical structure of chitin and its semicrystalline physical structure, it has been traditionally difficult to dissolve chitin. In the early studies of chitin fibers, inorganic concentrated solutions of hydrochloric acid and sulfuric acid were used to dissolve chitin .These solvents are, however, highly corrosive and the polymer solutions are not stable because chitin would undergo hydrolysis in a strong acidic condition. In 1936, Clark and Smith made a “syrupy colloidal solution” of chitin with aqueous lithium thiocyanate saturated at about 60°C and heated to 95°C. Further solvents for chitin were developed by Thor, utilizing the chitin xanthate.

The chitin was steeped in a concentrated NaOH solution at room temperature and then pressed to form an alkali chitin cake weighing approximately three times the weight of the original chitin. The pressed cake was then shredded and shaken in a closed vessel with carbon disulfide. After storing the mixture for several hours, the mixture was transferred to a Thermos jug and mixed with crushed ice. A chitin solution can be prepared after further mixing and storage.

A number of organic solvents for chitin were developed in the 1970s, as part of the renewed interest in chitin and chitosan. Austin [36] reported in 1975 a chitin solvent based on chloroalcohols in conjunction with aqueous solutions of mineral acids or organic acids. The chloroalcohols that may be used include

(1) 2-chloroethanol, Cl–CH2–CH2–OH;

(2) 1-chloro-2-propanol, Cl–CH2–CH(OH)–CH3;

(3) 2-chloro-1-propanol, CH3–CH(Cl)–CH2–OH;

(4) 3-chloro-1,2-propanediol, HO–CH2–CH(OH)– CH2–Cl.

Although a mixture comprising 1-chloro-2-propanol and 2-chloro-1-propanol may be used, the simple 2-chloroethanol was preferred. The solvent systems were reported to dissolve chitin rapidly at room or at a mildly elevated temperature, to give relatively low viscosity chitin solutions.

So far all the solvent systems used for dissolving chitin are acid-based, and some are very corrosive or expensive. The discovery of the aprotic solvent systems for chitin in about 1978 marked an important breakthrough in chitin research. The solvent involved the use of certain amides in conjunction with lithium chloride to dissolve chitin. The system has been found to provide the only medium in which the chitin is not hydrolyzed. In this method, dimethylacetamide (DMAc) and N-methyl-2-pyrrolidone (NMP) or mixtures of these amides in conjunction with LiCl dissolved chitin. It was found that the dissolution process was greatly improved when the original chitin was treated with p-toluene sulfonic acid in i-propanol. The treated chitin can be dissolved in DMAc containing about 7% LiCl to form a stable spinning solution.

THE PRODUCTION OF CHITIN FIBERS

All man-made fibers are generally made via three typical processes, i.e. melt-spinning, wet-spinning and dry-spinning. In the case of chitin and chitosan, the strong interchain forces as derived from the hydroxyl, acetamido and amino groups, raise the melting point of chitin and chitosan to well above their thermal degradation temperatures. Melt-spinning is therefore not possible with chitin and chitosan. Additionally, because of the strong polar groups in the two polymers, they can only be dissolved in polar solvents with high boiling temperatures, and dry-spinning, which produces fibers upon the evaporation of the solvent during extrusion, is also not practical. In most studies, chitin and chitosan fibers are made by the wet-spinning process, which produces fibers by first dissolving the polymer in a solvent and then extruding the polymer solution via fine holes into a nonsolvent. The polymer precipitates out in the form of a filament, which can be washed, drawn and dried to form the fibers. A typical wet-spinning production line is schematically presented in Fig

In the wet-spinning process in which most chitin fibers were made, a polymer solution is first made by dissolving the polymer in an appropriate solvent. The solution is then filtered and degassed before it is extended through fine holes into a nonsolvent to precipitate the polymer in a filament form (see Fig.). In the case of chitin fibers, the various studies, as reviewed in the previous sections, have developed a number of chitin solvents in which the chitin can be dissolved. Most of these studies succeeded in making chitin fibers of varying properties.

Economic aspects

The production of chitin and chitosan is currently based on crab and shrimp shells discarded by the canning industries in Oregon, Washington, Virginia and Japan and by various finishing fleets in the Antarctic. Several coun-tries possess large unexploited crustacean re-sources, e.g. Norway, Mexico and Chile . The production of chitosan from crustacean shells obtained as a food industry waste is economically feasible, especially if it includes the recovery of carotenoids. The shells contain considerable quantities of astaxanthin, a carot-enoid that has so far not been synthesized, and which is marketed as a fish food additive in aquaculture, especially for salmon.

To produce 1 kg of 70% deacetylated chitosan from shrimp shells, 6.3 kg of HCl and 1.8 kg of NaOH are required in addition to nitrogen, process water (0.5 t) and cooling water (0.9 t). Important items for estimating the production cost include transportation, which varies depending on labor and location.

In India, the Central Institute of Fisheries Technology, Kerala, initiated research on chitin and chitosan. From their investigation, they found that dry prawn waste contained 23% and dry squilla contained 15% chitin . They have also reported that the chitinous solid waste fraction of the average Indian landing of shell fish ranges from 60 000 to 80 000 tonnes. Chitin and chitosan are now produced commer-cially in India, Japan, Poland, Norway and Australia. The worldwide price of chitosan (in small quantities) is ca. US$7.5 / 10 g (Sigma and Aldrich price list).

Chitosan Chitosan is a linear polysaccharide produced by the deacetylation of chitin, a naturally occurring polymer. The effect of the degree of deacetylation on properties such as solubility and antimicrobial activity have been studied in several articles. Chitosan is widely used in a range of diverse fields, including waste management, medicine, food and agriculture. 

Chitosan has unique biological properties such as biocompatibility, antimicrobial, biogradeable, mucoadhesion, anticholesterolemic and permeation enhancement effects. These properties have led to its increased utility in specific applications such as antibacterial/anti-biofouling coatings, controlled release coatings and microcapsules, nanofiltration, drug delivery hydrogels, gene delivery and tissue engineering scaffolds.

Chitosan exists naturally only in a few species of fungi. Commercially, chitosan is produced from chitin by deacetylating with concentrated alkali solutions at elevated temperatures. The acetamide groups undergo hydrolysis, and chitosan is formed.

THE PRODUCTION OF CHITOSAN FIBERS

Despite the advantage of chitosan being an easily soluble polymer, few reports were found in the literature dealing with the production of chitosan fibers. It was only in 1980 that the first attempt was reported for making chitosan fibers. It was claimed that chitosan fibers could be produced by first dissolving its acetate in water . The concentrated solution, typically 3% chitosan dissolved in 0.5% aqueous acetic acid, can be extruded into a 5% aqueous NaOH bath. The resultant fibers possessed a tenacity of 2.44 g/denier, an elongation at break of 10.8% and a knot strength of 1.75 g/denier.

-Chitosan fibers were also made with di-chloroacetic acid as the solvent acid and CuCO3–NH4OH as the coagulant . A further report on chitosan fibers used urea–acetic acid mixture as the solvent .

Later in preparing fibers from chitosan with various degrees of deacetylation, Tokura et al. reported that chitosan fibers can be prepared by extruding dopes in 2–4% aqueous acetic acid into a bath containing CuSO4–NH4OH or CuSO4–H2SO4. The fibers obtained were a complex of chitosan and copper; the latter can be removed afterwards.

East and Qin reported that chitosan fibers can be made by extruding the chitosan solution in 2% aqueous acetic acid solution. The fibers can be made by precipitating the chitosan in a dilute alkali solution. After drawing, washing and drying, continuous chitosan filaments can be made.

It was found that the spinning variables such as jet stretch ratio, draw ratio and coagulation bath composition had little effect on the fiber properties, though higher draw ratios would be obtained at lower jet stretch ratios and slightly improved fiber tenacities were obtained by using more dilute NaOH solutions as the coagulant. The drying conditions, however, had a big effect on the fiber properties. The fiber obtained by air drying had a much higher extensibility than those dried by radiant heating. Strong fibers were obtained by using a coagulation bath containing a concentrated Na2SO4 with a small amount of NaOH.

THE CHEMISTRY OF CHITIN AND CHITOSAN

Chemically, chitin and chitosan can be regarded as derivatives of cellulose in which the C-2 hydroxyl group in cellulose is replaced by an acetamide group and a free amine group in chitin and chitosan respectively. In the case of chitin, the polymer is relatively inert due to the chemically inert acetamide group, and in the case of chitosan, the polymer is highly reactive due to the free amine groups. Both chitin and chitosan, however, can undergo most reactions that are applied to cellulose. As has been mentioned before, chitin and chitosan are polysaccharides consisting of 2-acetamido-2-deoxy-b-D-glucose and 2-amino- 2-deoxy-b-D-glucose as the repeating units respectively. However, pure chitin with 100% acetylation on the amine groups and pure chitosan with 100% deacetylation rarely exist. Chitin and chitosan often exist as a copolymer of glucosamines and acetylated glucosamines. The degree of acetylation is therefore one of the most important structural parameters in chitin and chitosan.

It is commonly accepted that chitin is defined as the polymer in which the majority of the amine groups are acetylated while in chitosan, the majority of the amine groups are primary amine. Over the years, many attempts have been made to modify the properties of chitin and chitosan by using various reactions involving the –OH and –NH2 groups. Some of the typical reactions are briefly summarized below:

Chitosan Salts

As chitosan contains the basic free amines, it can form salts with a variety of inorganic and organic acids. Most of these salts are water-soluble. The chitosan salt solutions can be dried and ground to form powders [19] which can be highly purified to provide a water-soluble raw material for various uses.

N-acylation

Acylation of the amine groups of chitosan can be readily carried out using acyl anhydride as the reactant. During the acylation process of a chitosan solution, the chitosan slowly loses the solubility and a gel is formed. This gelation process was studied by a number of workers and various parameters such as the size of the acyl groups, the reaction temperature and reactant concentration, and the solvent media, were investigated. The acetylation of chitosan leads to a regenerated chitin. It was found that the chitosan fibers can be readily acetylated using acetic anhydride in methanol as the solvent. The regenerated chitin fibers were found to have similar properties to those of the natural chitin fibers.

Schiff Bases and their Reduced Products

It is well known that Schiff bases can be formed by the reaction between amines and aldehydes or ketones. It is reported that chitosan reacts rapidly with aldehyde in aqueous acid solutions. Using a 5% chitosan dissolved in 10% acetic acid solution, gels formed when the mixture of chitosan and some aldehydes was stored overnight. In another study, Muzzarelli and Rocchetti modified chitosan with aldehyde acids and keto acids, from which they obtained a series of polymers with carboxyls, primary and secondary amines and hydroxyl groups. The products showed excellent chelating properties. In one example, 10 g of chitosan was suspended in 1.5 l of water and an excess of keto-acid was added. The pH was slowly adjusted to 4.5 with 0.2 M NaOH. The insoluble product was then reduced with sodium cyanoborohydride dissolved in water and the pH was finally adjusted to about 7 with 1 M NaOH. After 48 hours, the polysaccharide in the amino acid form was washed, dialyzed against water and isolated.

Reaction with Halogen-substituted Compounds

Both the –OH and –NH2 groups are reactive with halogen-substituted compounds. This offers an easy way for the structural modifications of chitin and chitosan, resulting in various alkylated chitins and chitosans with a variety of properties . Typically, alkylation of chitin and chitosan with alkyl halides is carried out under basic conditions. However, in all circumstances, –NH2 is more reactive than –OH and therefore, in order to retain the amine groups in chitosan , suitable precautions need to be taken. O-substitution can be carried out by first protecting the amine

groups using Schiff base reaction. After the O-modification, the Schiff base can be removed by the action of acetic acid, thus regenerating the free amine groups.

Chelation of Metal Ions

The ability of chitin and chitosan to absorb heavy metal ions is well known. The mechanism was, however, not well defined until Muzzarelli pointed out the chelating properties of chitin and chitosan. It has been shown by many workers that chitin and chitosan form metal ion complexes with many transition metal ions. A number of mechanisms have been suggested, with the –NH2 and/or the –OH groups involved in the complex. In a recent study on the chelation properties of chitosan fibers, it has been demonstrated that the absorption of Cu (II) by chitosan fibers is proportional to the degree of deacetylation, with a molar ratio of Cu(II) to amine of about 3. This result confirms the fact that the chelating properties is mainly as a result of the primary amine groups in chitin and chitosan. The interaction of the first row transition metal ions with chitin and chitosan is accompanied by the appearance of color in almost all instances, namely red with titanium, orange with metavanadate, green with trivalent chromium and orange with hexavalent chromium, yellowish-brown with divalent iron, yellowish green with trivalent iron, pink with cobalt, green with nickel and blue with copper. In terms of the affinity of metal ions to chitin and chitosan, Muzzarelli observed that chitosan absorbed metal ions in the order Cu>Ni>Zn>Co> Fe>Mn, in a 0.1 M potassium chloride solution. Koshijima et al. found the order to be Hg>Cu> Fe>Ni>Cd>Mn>Co>Pb for a 0.15 M Na2SO4 solution, while Yoshinari and Subramanian [30] recognized the order to be Ni>Zn>Co>Cu>Pb> Fe=Mn>Mg>Ca for chitin. In a study on metal ion uptake onto chitosan using ion-selective electrodes, Kawano found the order to be Hg>Ag> Cu>Cd>Pb. Further, the effect of anions was found in the order of CuSO4>Cu (Ac) 2>CuCl2> Cu(NO3)2.

PROPERTIES of CHITIN AND CHITOSAN FIBERS

Tensile/Mechanical Properties

As has been mentioned previously, chitin and chitosan fibers of various tensile/mechanical properties can be made with a variety of spinning conditions. In certain respects, the fiber properties are affected by the production conditions rather than by their chemical nature. Typically, chitin and chitosan fibers have similar tensile/mechanical properties to those of viscose rayon fibers. The typical fibers have tenacities of about 2 g/denier and extensibilities of about 10%. Higher fiber strengths have been reported by using special spinning conditions such as the dry-jet wet-spinning technique and the use of special solvent system to obtain a liquid crystal phase for the chitin and chitosan solutions.

East and Qin reported that when the chitosan fibers are acetylated to produce the chitin fibers, the fiber dry strength increased with the increasing extent of acetylation. The fiber wet strength showed an initial decrease but increased significantly upon further increase in the degree of acetylation. It is known that chitin is a highly crystalline polymer because of the ability of the acetamide groups to form hydrogen bondings. The increase of both the dry and wet strengths with the increase in the degree of acetylation is a reflection of the increase in the interchain forces and the increase in the degree of crystallinity, as can be seen in the Xray diffraction patterns of the original chitosan fibers and that of the same fiber after acetylation . The initial drop in the wet strength of the fiber indicates the fact that for the partially acetylated fibers, the polymer structure is a highly irregular copolymer consisting of glucosamines and acetyl glucosamines. This irregular structure causes the deterioration of the wet strength of the fiber.

The strength of the chitosan fibers is highly sensitive to the moisture regain of the fiber. As is shown in, when the chitosan yarns are conditioned under different relative humidities, the moisture regain increases dramatically, while at the same time, the breaking strength of the fiber showed a significant reduction.

Physical/Thermal Properties

Both chitin and chitosan are semicrystalline polymers capable of forming a three-dimensionally ordered structure. Chitin can be formed into three types of crystal structures, i.e. a-chitin, b-chitin and g-chitin. It is reported that the properties of the natural chitin varies with different types of poly- morphic forms, i.e. while a-chitin is usually found where extreme hardness is required, b- and g-chitins provide toughness, flexibility and mobility. The crystal structures of chitin have been studied by many workers [54–59]. It is now generally agreed that a-chitin is composed of antiparallel chains alternatively arranged in “up” and “down” configurations. When the crystal structures of chitin and cellulose are compared, the a-chitin is analogous to cellulose II. In b-chitin, the chitin chains are arranged in a parallel form, i.e. all the molecules in the crystal are pointing in the same direction. b-Chitin is reported to be least crystalline and it swells greatly in water. g-Chitin is composed of parallel and antiparallel chains and has properties intermediate of a and b-chitin. In g-chitin, every two “up” chains are accompanied by one “down” chain.

Chitin fibers have a semicrystalline structure. The fibers can also be made into a highly oriented structure when they are stretched, especially in the dry-jet wet-spinning process, where the as-spun fibers are capable of a high degree of stretching. A typical X-ray diffraction pattern of an oriented chitin fiber is shown in Figure.

The thermal properties of chitin and chitosan fibers are similar to those of cellulosic fibers. They do not melt but degrade at elevated temperatures. In an inert atmosphere, the chitosan fibers degrade at a lower temperature than the chitin fibers. This can be seen in the thermal gravimetric curve of partially acetylated chitosan fibers (Fig. ).

The two peaks indicate the relative amount of glucosamine and acetyl glucosamine present in the fiber.

Some typical properties of chitin and chitosan fibers are compared with other natural and manmade fibers in Table

.

Applications of chitin and chitosanThe interest in chitin originates from the study of the behaviour and chemical characteris-tics of lysozyme, an

enzyme present in human body fluids. A wide variety of medical applications for chitin and chitin derivatives have been reported over the last three decades. It has been suggested that chitosan may be used to inhibit fibroplasia in wound healing and to promote tissue growth and differentiation in tissue culture.

The poor solubility of chitin is the major limiting factor in its utilization. Despite this limitation, various applications of chitin and modified chitins have been reported, e.g. as raw material for man-made fibres. Fibres made of chitin and chitosan are useful as absorb-able sutures and wound-dressing materials. Chitin sutures resist attack in bile, urine and pancreatic juice, which are problem areas with other absorbable sutures. It has been claimed that wound dressings made of chitin and chitosan fibres have applications in wastewater treatment. Here, the removal of heavy metal ions by chitosan through chelation has received much attention. Their use in the apparal industry, with a much larger scope, could be a long-term possibility.

• Photography

Chitosan has important applications in photo-graphy due to its resistance to abrasion, its optical characteristics, and film forming ability. Silver complexes are not appreciably retained by chitosan and therefore can easily be pene-trated from one layer to another of a film by diffusion .

• Cosmetics

For cosmetic applications, organic acids are usually good solvents, chitin and chitosan have fungicidal and fungistatic properties. Chitosan is the only natural cationic gum that becomes viscous on being neutralized with acid. These materials are used in creams, lotions and perma-nent waving lotions and several derivatives have also been reported as nail lacquers.

• Chitosan as an artificial skin

Individuals who have suffered extensive losses of skin, commonly in fires, are actually ill and in danger of succumbing either to massive infection or to severe fluid loss. Patients must often cope with problems of rehabilitation arising from deep, disfiguring scars and crippling contractures. Malette et al. studied the effect of treatment with chitosan and saline solution on healing and fibroplasia of wounds made by scalpel insertions in skin and subcutaneous tissue in the abdominal surface of dogs.

A. Chitin - and chitosan - based dressings

Chitin and chitosan have many distinctive biomedical properties. However, chitin-based wound healing products are still at the early stages of research .

Sparkes and Murray developed a surgical dressing made of a chitosan–gelatin complex. The procedure involves dissolving the chitosan in water in the presence of a suitable acid, maintaining the pH of the solution at about 2–3, followed by adding the gelatin dissolved in water. The ratio of chitosan and gelatin is 3:1 to 1:3. To reduce the stiffness of the resulting dressing a certain amount of plasticizers such as glycerol and sorbitol could be added to the mixture. Dressing film was cast from this solution on a flat plate and dried at room temperature. It was claimed that, in contrast to conventional biological dressings, this experimental dressing displayed excellent adhesion to subcutaneous fat.

The British Textile Technology Group (BTTG) patented a procedure for making a chitin-based fibrous dressings. In this method the chitin / chitosan fibres were not made by the traditional fibre-spinning technique and the raw materials were not from shrimp shell but from micro-fungi instead. The procedure can be summarized as follows.

(i) Micro-fungal mycelia preparation from a culture of Macro mucedo growing in a nutrient solution.

(ii) Culture washing and treatment with NaOH to remove protein and precipitate chitin / chitosan. (iii) Bleaching and further washing.

(iv) Preparation of the dispersion of fibres using paper-making equipment.

(v) Filtration and wet-laid matt preparation; mixing with other fibres to give mechanical strength.

This is a novel method, which uses a non-animal source as the raw material, and the resulting micro-fungal fibres are totally different from normal spun fibres. They have highly branched and irregular structures. The fibres are unmanageably brittle when they are allowed to dry and a plasticizer has to be associated with the whole process and a wet-laid matt is used as the basic product.

As far as chitin-based commercial wound dressings are concerned, one product (Beschitin , Unitika) is commercially available in Japan, which is a nonwoven fabric manufactured from chitin filaments.

• Food and nutrition

The N-acetylglucosamine (NAG) moiety present in human milk promotes the growth of bifido bacteria, which block other types of microorganism and generate the lactase required

for digestion of milk lactose. Cow’s milk contains only a limited amount of the NAG moiety, hence some infants fed cow’s milk may have indigestion. Many animals and some humans (including the elderly) have similar lactose intolerances .

Animal nutritional studies have shown that the utilization of whey may be improved if the diet contains small amounts of chitinous material. This improvement is attributed to the change in the intestinal microflora brought about by the chitinous supplement. Chickens fed a commercial broiler diet containing 20% dried whey and 2 or 0.5% chitin had significantly improved weight again compared to controls. The feed efficiency ratio shifted from 2.5 to 2.38 due to incorporation of chitin in the feed.

• Ophthalmology

Chitosan possesses all the characteristics required for making an ideal contact lens: optical clarity, mechanical stability, sufficient optical correction, gas permeability, particularly to-wards oxygen, wettability and immunological compatibility. Contact lenses are made from partially depolymerized and purified squid pen chitosan by spin casting technology and these contact lenses are clear, tough and possess other required physical properties such as modulus, tensile strength, tear strength, elongation, water content and oxygen permeability. The anti-microbial and wound healing properties of chitosan along with an excellent film capability make chitosan suitable for development of ocular bandage lenses .

• Water engineering

As environmental protection is becoming an important global problem, the relevant industries pay attention to the development of technology which does not cause environmental problems.

A. Metal capture from wastewater

Chitosan is used for adsorption purposes of Hg and Cd ions

McKay et al. used chitosan for the removal of Cu 21, Hg 21, Ni 21 and Zn 21 within the temperature range 25–608C at near neutral pH. Further adsorption parameters for the removal of these metal ions were reported by Yang et al. Maruca et al. used chitosan flakes of 0.4–4 mm for the removal of Cr(III) from wastewater. The adsorption capacity increased with a decrease in the size of the flakes, which implied that metal ions were preferably adsorbed on the outer surface of chitosan in the removal of Cr(III) from the wastewater.

B Colour removal from textile mill effluents

Sorption of dyes

No single decolorization method is likely to be the optimum for all wastewater streams. Due to its unique molecular structure, chitosan has an extremely high affinity for many classes of dyes, including disperse, direct, reactive, acid, vat, sulfur and naphtha dyes. The rate of diffusion of dyes in chitosan is similar to that in cellulose. Only for basic dyes has chitosan a low affinity. Chitosan is versatile in sorbing metals and surfactants, as well as to derivatization to attract basic dyes and other moieties (e.g., proteins from food processing plants).

The sorption of dyes by chitosan is exothermic, an increase in the temperature leads to an increase in the dye sorption rate, but diminishes total sorption capacity . However, these effects are small and normal wastewater temperature variations do not significantly affect the overall decolorization performance. Also, the wastewater pH may be an important factor in the sorption of certain dyes onto chitosan because, at low pH, chitosan’s free amino groups are protonated, causing them to attract anionic dyes. Contact time or, inversely, flux (wastewater flow per unit cross-sectional area) affects sorption in a complex manner in a fixed bed design reactor system due to contact time, bed penetration and boundary layer effects. At high flux, the diversion of liquid into larger channels around particles and turbulent flow occur. In general, a low flux tends to give more complete contaminant removal.

Finally, a factor which significantly increases the sorption rate is the loading thermodynamics, which indicates whether a reaction is favoured. As loading increases, the driving forces for sorption decrease, leading to an ultimate saturation value beyond which further sorption is not possible.

• Paper finishing

Chitosan has been reported to impart wet strength to paper . Hydroxymethyl chitin and other water-soluble derivatives are useful end additives in paper making. This polymer, although potentially available in large quantities, never became a commercially significant product. The entrepreneur in paper making can utilize this polymer for better finish paper properties.

• Solid-state batteries

Chitosan is insoluble in water. This poses a problem in the fabrication of solid-state proton-conducting batteries because there will not be any water present in the chitosan which can act as a source of hydrogen ions. In other words, the proton-conducting polymer needed for solid-state battery application cannot be obtained from chitosan alone. Chitosan is a biopolymer which can provide ionic conductivity when dissolved in acetic acid. The conductivity is due to the presence of protons from the acetic acid solution. The transport of these protons is thought to occur

through many microvoids in the polymer since the dielectric constants from piezoelectric studies are small. The choice of a more suitable electrode material may produce a better battery system.

• . Drug-delivery systems

Controlled-release technology emerged during the 1980s as a commercially sound methodology. The achievement of predictable and reproducible release of an agent into a specific environment over an extended period of time has much significant merit. It creates a desired environment with optimal response, minimum side-effects and prolonged efficacy. Controlledrelease dosage forms enhance the safety, efficacy and reliability of drug therapy. They regulate the drug release rate and reduce the frequency of drug administration to encourage patients to comply with dosing instructions. Conventional dosage forms often lead to wide swings in serum drug concentrations. Most of the drug content is released soon after administration, causing drug levels in the body to rise rapidly, peak and then decline sharply. For

drugs whose actions correlate with their serum drug concentration, the sharp fluctuations often cause unacceptable side-effects at the peaks, followed by inadequate therapy at the troughs .

A new dimension is the incorporation of biodegradability into the system. A number of degradable polymers are potentially useful for this purpose, including synthetic as well as natural substances .

The release of drugs, absorbed or encapsulated by polymers, involves their slow and controllable diffusion from / through polymeric materials. Production of slow release (SR) drugs by the pharmaceutical industry is now a matter of routine. Drugs covalently attached to biodegradable polymers or dispersed in a polymeric matrix of such macromolecules may be released by erosion / degradation of the polymer. Therapeutic molecules, complexed by polymers, may also be released from gels by diffusion.

Chitosan is non-toxic and easily bioabsorbable with gel-forming ability at low pH. Moreover, chitosan has antacid and antiulcer activities which prevent or weaken drug irritation in the stomach. Also, chitosan matrix formulations

appear to float and gradually swell in an acid medium. All these interesting properties of chitosan make this natural polymer an ideal candidate for controlled drug release formulations. Many excellent reviews and books deal with the properties, chemistry, biochemistry and applications of chitin, chitosan and their derivatives.

Hydrogels based on chitin and chitosan

Hydrogels are highly swollen, hydrophilic polymer networks that can absorb large amounts of water and drastically increase in volume. It is well known that the physicochemical properties of the hydrogel depend not only on the molecular structure, the gel structure, and the degree of cross linking, but also on the content and state of the water in the hydrogel. Hydrogels have been widely used in controlled-release systems .

Recently, hydrogels which swell and contract in response to external pH have been explored. The pH-sensitive hydrogels have potential use in site-specific delivery of drugs to specific regions of the gastrointestinal tract (GI) and have been prepared for low molecular weight and protein drug delivery . It is known that the release of drugs from hydrogels depends on their structure or their chemical properties in response to pH . These polymers, in certain cases, are expected to reside in the body for a longer period and respond to local environmental stimuli to modulate drug release. Sometimes the polymers used are biodegradable to obtain a desirable device to control drug release. Thus, to be able to design hydrogels for a particular application, it is important to know the nature of the systems in their environmental conditions.

Chitin and chitosan tablets

Many direct-compression diluents have been reported in the literature, but every diluent has some disadvantages microcrystalline cellulose (MCC) has been widely used as a tablet diluent in Japan. Chitin and chitosan, because of their versatility, have been reported to be useful diluents in pharmaceutical preparations

Microcapsules / microspheres of chitosan

A ‘microcapsule’ is defined as a spherical particle with size varying from 50 nm to 2 mm, containing a core substance. Microspheres are, in a strict sense, spherical empty particles. However, the terms microcapsules and micro-spheres are often used synonymously. In addition, some related terms are used as well. For example, ‘microbeads’ and ‘beads’ are used alternatively. Spheres and spherical particles are also used for a large size and rigid morphology. Recently, Yao et al. highlighted the preparation and properties of microcapsules and microspheres related to chitosan. Due to the attractive properties and wider applications of chitosan-based microcapsules and microspheres, a survey of the applications in controlled drug release formulations is appropriate. Moreover, microcapsule and microsphere forms have an edge over other forms in handling and administration.

5

Table Chitin derivatives and their proposed uses

Derivative Examples Potential uses

N-Acyl chitosans Formyl, acetyl, propionyl, butyryl, hexanoyl, Textiles, membranesoctanoyl, decanoyl, dodecanoyl, tetradecanoyl, and medical aidslauroyl, myristoyl, palmitoyl, stearoyl, benzoyl,monochloroacetoyl, dichloroacetyl, trifluoroacetyl,carbamoyl, succinyl, acetoxybenzoyl

N-Carboxyalkyl N-Carboxybenzyl, glycine-glucan (N-carboxy- Chromatographic(aryl) chitosans methyl chitosan), alanine glucan, phenylalanine media and metal

glucan, tyrosine glucan, serine glucan, glutamic ion collectionacid glucan, methionine glucan, leucine glucan

N-Carboxyacyl From anhydrides such as maleic, itaconic, acetyl- ?Chitosans thiosuccinic, glutaric, cyclohexane 1,2-dicarbox-

cyclic, phthalic, cis-tetrahydrophthalic, 5-norbo-rnene-2,3-dicarboxylic, diphenic, salicylic, tri-mellitic, pyromellitic anhydride

o-Carboxyalkyl o-Carboxymethyl, crosslinked o-carboxymethyl Molecular sieves,Chitosans viscosity builders,

and metal ion collec-tion

Sugar derivatives 1-Deoxygalactic-1-yl-, 1-deoxyglucit-1-yl-,1-deoxymelibiit-1-yl-, 1-deoxylactit-1-yl-,1-deoxylactit-1-yl-4(2,2,6,6-tetramethylpiperidine--1-oxyl)-, 1-deoxy-69-aldehydolactit-1-yl-,1-deoxy-69-aldehydomelibiit-1-yl-, cellobiit-1-yl-chitosans, products obtained from ascorbic acid

Metal ion chelates Palladium, copper, silver, iodine Catalyst, photography,health products, andinsecticides

Semi synthetic resins Copolymer of chitosan with methyl methacrylate, Textilesof chitosan polyurea-urethane, poly(amideester), acrylamide-

maleic anhydride

Natural polysacchar- Chitosan glucans from various organisms Flocculation andide complexes, metal ion chelationMiscellaneous Alkyl chitin, benzyl chitin Intermediate, serine

protease purificationHydroxy butyl chitin, cyanoethyl chitosan Desalting filtration,

dialysis and insulatingpapers

Hydroxy ethyl glycol chitosan Enzymology, dialysisand special papers

Glutaraldehyde chitosan Enzymeimmobilization

Linoelic acid–chitosan complex Food additive andanticholesterolemic

Uracylchitosan, theophylline chitosan, adenine-chitosan, chitosan salts of acid polysaccharides,chitosan streptomycin, 2-amido-2,6-diaminohep-tanoic acid chitosan

• Biotechnology

A. Preparation of biotechnological materials

Chitin has two hydroxyl groups, while chitosan has one amino group and two hydroxyl groups in the repeating hexosamide residue. Chemical modification of these groups and the regeneration reaction gives rise to various novel biofunctional macromolecular products having the original organization or new types of organization.

B. Cell - stimulating materials

(i) In plants

Soya beans were coated with a thin layer of depolymerized chitin, carboxymethyl (CM)-chitin and hydroxyethyl (HE)-chitin, and the seeds were cultured in the field. It was observed that the seed chitinase increased 1.5–2.0-fold, the seed germination rate increased by 6%, the pod number increased by 9%, the plant dry weight increased by 8%, and the crop yield also increased by 10–12% over the control.

Dressing with chitin films, sponges and fibres enhanced chitinase activity in tree-bark tissues around wounds up to four-fold over the control. The chitin films, which were implanted in or used to dress the tree-bark tissues, were digested within 4 to 24 weeks thereafter and were assimilated into the wounded bark tissues. The fate of N-acetyl-D-glucosamine in plant tissue is unknown. Phenylalanine ammonia-lyase was stimulated by treatment with chitin, and lignin formation in the plant increased. As a result, wound healing was accelerated.

(ii) In animals

Extracellular lysozyme activity was enhanced in vitro cultures of several mammalian cells by treatment with chitin and its derivatives. As a result, connective tissue formation was stimulated, and the self-defense function against microbial infection was enhanced at the cellular level. On the basis of these results, several chitin and chitosan dressing materials (discussed in the foregoing sections) have been developed commercially for the healing treatment of human and animal wounds.

C. Antibacterial agents

The growth of Escherichia coli was inhibited in the presence of more than 0.025% chitosan. Chitosan also inhibited the growth of Fusarium and Alternaria. The cationic amino groups of chitosan probably bind to anionic groups of these microorganisms, resulting in growth inhibition.

D. Blood anti - coagulants (heparinoids)

Chitin and chitosan sulphates have blood anticoagulant and lipoprotein lipase (LPL)-re-leasing activities. Chitin 3,6-sulfate showed about two-fold anticoagulant activity and 0.1-fold LPL-releasing activity over those of heparin; the sulfate derivatives might be usable as heparinoids for artificial blood dialysis .

E. Anti - throbogenic and haemostatic materials

Chitosan fibres were found to be thrombogenic and haemostatic in an in vitro test, and N-hexanoyl and N-octanoyl chitosan fibres were anti-thrombogenic. Chitosan fibres can be used as haemostatic material; N-hexanoyl and N-octanoylchitosan fibres are used as anti-thrombogenic materials.

• Chitosan as fat trapper

One of the characters in a recent movie, ‘The Full Monty’, had a memorable line: ‘‘The less I eat, the fatter I get.’’ It’s a phenomenon that plagues many dieters who eat less and lose muscle instead of fat. As a result, their metabolism slows down and it becomes more and more difficult to control weight. Fortunately, it is not too difficult to lose the right stuff, fat, while improving muscle tone, metabolism and health. Many supplements can help in the fat reduction process, including pyruvate and chitosan. Pyru-vate, found in red apples, some types of cheese, and red wine, stimulates fat loss and boosts exercise performance. Chitosan attaches itself to fat in the stomach before it is digested, thus trapping the fat and preventing its absorption by the digestive tract. Fat in turn binds to the chitosan fibre, forming a mass which the body cannot absorb, and which is eliminated by the body.

Conclusion

Most of the biodegradable materials currently on the market are based on natural polymers such as collagen and synthetic polymers such as poly(aesters). Advances in synthetic organic chemistry and novel bioprocesses are enabling the development ofa wide range of novel polymeric materials are used as candidates for developing transient implants and drug delivery vehicles. The success of biodegradable implants lies in our ability to custom design or modifies existing biomaterials to achieve appropriate biocompatibility, degradation and physical properties to elicit favorable biological responses. Chitin and chitosan are rich renewable natural resource that can be used for many applications. Fibers from chitin and chitosan provide both the unique properties derived from the chemical, physical and biomedical natures of the poly acetyl glucosamine and polygluosamine, and the physical and mechanical properties of the fibrous structure, which can be easily extended into three-dimensional structures of woven, knitted and nonwoven fabrics. Chitin and chitosan fibers can be made in a variety of different solvent systems and spinning conditions. These fibers have good tensile and mechanical properties for further processing’s and it can be reasonably claimed that the chitin and chitosan fibers can be utilized in a number of potential applications, offering the unique properties of these two polymers.

Chitin and chitosan have a wide range of applications. They may be employed, for example, to solve numerous problems in environmental and biomedical engineering. Chitin derivatives including partially deacetylated chitosan can be easily molded to various forms and their derivatives are digested in vivo by lysozomal enzymes. Thus, it appears that this material can be a most interesting candidate for use as a carrier of a variety of drugs for controlled-release applications. Lately, the transdermal absorption promoting characteristics of chitosan have been exploited, especially for nasal and oral delivery of polar drugs to include peptides and proteins and for vaccine delivery. These properties, together with the very safe toxicity profile, make chitosan an exciting and promising incipient for the pharmaceutical industry for present and future applications. Thanks to the bioactivities of chitosan itself, its formulations with drugs may have dual therapeutic effects.

References

1) Chitosan—A versatile semi-synthetic polymer in biomedical applications2) Chitin and chitosan nanofibers: electro spinning of chitin and deacetylation of chitin nanofibers3) Biodegradable polymers as biomaterials4) Chitin and chitosan polymers: Chemistry, solubility and fiber formation5) A review of chitin and chitosan applications6) Chitosan-modifications and applications: Opportunities galore7) Preparation, Characterization, and Properties of &Chitin and N-acetylated &Chitin8) Chitin and Chitosan Fibers9) Miscibility and Biodegradability of Silk Fibroin/Carboxymethyl Chitin Blend Films10) A review of chitin and chitosan applications’11) Novel chitin and chitosan nanofibers in biomedical applications12) Biomedical Activity of Chitin/Chitosan Based Materials— Influence of Physicochemical Properties Apart

from Molecular Weight and Degree of N-Acetylation