1

Reactive & Functional Polymers 46 (2000) 127
www.elsevier.com / locate / react
Review
A review of chitin and chitosan applications q

Majeti N.V. Ravi Kumar*
Department of Chemistry, University of Roorkee, Roorkee 247 667, India
Received 24 January 2000; received in revised form 20 June 2000; accepted 25 June 2000
Abstract
Chitin is the most abundant natural amino polysaccharide and is estimated to be produced annually almost as much as
cellulose. It has become of great interest not only as an underutilized resource, but also as a new functional material of high
potential in various fields, and recent progress in chitin chemistry is quite noteworthy. The purpose of this review is to take a
closer look at chitin and chitosan applications. Based on current research and existing products, some new and futuristic
approaches in this fascinating area are thoroughly discussed. 2000 Elsevier Science B.V. All rights reserved.
Keywords: Beads; Biotechnology; Chitin; Chitosan; Controlled drug delivery; Fibers; Nanoparticles; Hydrogels; Tablets; Transdermal
devices
1. Introduction
Chitin, a naturally abundant mucopolysaccharide, and the supporting material of crustaceans, insects, etc., is well known to consist of
2-acetamido-2-deoxy-b-D-glucose through a b
(1 4) linkage. Chitin can be degraded by
chitinase. Its immunogenicity is exceptionally
low, in spite of the presence of nitrogen. It is a
highly insoluble material resembling cellulose
in its solubility and low chemical reactivity. It
may be regarded as cellulose with hydroxyl at
q
This paper is dedicated to Professor M.N.V. Prasad, Ph.D.,
FNIE (New Delhi), DSc. (hc Colombo), School of Life Sciences,
University of Hyderabad, Hyderabad, India, who inspired me with
his scientific approach, honesty and human warmth.
*Post Bag No. 29, Roorkee 247 667, India. Fax: 191-133273560.
E-mail address: mnvrkumar@mailcity.com (M.N.V. Ravi
Kumar).
position C-2 replaced by an acetamido group.

Like cellulose, it functions naturally as a structural polysaccharide. Chitin is a white, hard,
inelastic, nitrogenous polysaccharide and the
major source of surface pollution in coastal
areas. Chitosan is the N-deacetylated derivative
of chitin, although this N-deacetylation is almost never complete. A sharp nomenclature
with respect to the degree of N-deacetylation
has not been defined between chitin and
chitosan [1,2]. The structures of cellulose, chitin
and chitosan are shown in Fig. 1. Chitin and
chitosan are of commercial interest due to their
high percentage of nitrogen (6.89%) compared
to synthetically substituted cellulose (1.25%).
This makes chitin a useful chelating agent [1].
As most of the present-day polymers are synthetic materials, their biocompatibility and
biodegradability are much more limited than
those of natural polymers such as cellulose,
1381-5148 / 00 / $ see front matter 2000 Elsevier Science B.V. All rights reserved.
PII: S1381-5148( 00 )00038-9
M.N.V. Ravi Kumar / Reactive & Functional Polymers 46 (2000) 1 27
radability, non-toxicity, adsorption properties,

etc.
Recently, much attention has been paid to
chitosan as a potential polysaccharide resource
[5]. Although several efforts have been reported
to prepare functional derivatives of chitosan by
chemical modifications [68], very few attained
solubility in general organic solvents [9,10] and
some binary solvent systems [1113]. Chemically modified chitin and chitosan structures
resulting in improved solubility in general organic solvents have been reported by many
workers [1423]. The present review is an
attempt to discuss the current applications and
future prospects of chitin and chitosan.
2. Processing of chitin and chitosan
Fig. 1. Structures of cellulose, chitin and chitosan.
chitin, chitosan and their derivatives. However,

these naturally abundant materials also exhibit a
limitation in their reactivity and processability
[3,4]. In this respect, chitin and chitosan are
recommended as suitable functional materials,
because these natural polymers have excellent
properties such as biocompatibility, biodeg-
Chitin is easily obtained from crab or shrimp

shells and fungal mycelia. In the first case,
chitin production is associated with food industries such as shrimp canning. In the second case,
the production of chitosanglucan complexes is
associated with fermentation processes, similar
to those for the production of citric acid from
Aspergillus niger, Mucor rouxii, and Streptomyces, which involves alkali treatment yielding chitosanglucan complexes. The alkali removes the protein and deacetylates chitin simultaneously. Depending on the alkali concentra-
Scheme 1.
tion, some soluble glycans are removed [24].

The processing of crustacean shells mainly
involves the removal of proteins and the dissolution of calcium carbonate which is present in
crab shells in high concentrations. The resulting
chitin is deacetylated in 40% sodium hydroxide
at 1208C for 13 h. This treatment produces
70% deacetylated chitosan (Scheme 1).
3. 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 countries possess large unexploited crustacean resources, e.g. Norway, Mexico and Chile [25].
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 carotenoid 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 [26]. 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 [27,28].
Chitin and chitosan are now produced commercially 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).
4. Properties of chitin and chitosan

Most of the naturally occurring polysaccharides, e.g. cellulose, dextran, pectin, alginic
acid, agar, agarose and carragenans, are neutral
or acidic in nature, whereas chitin and chitosan
are examples of highly basic polysaccharides.
Their unique properties include polyoxysalt
formation, ability to form films, chelate metal
ions and optical structural characteristics [29].
Like cellulose, chitin functions naturally as a
structural polysaccharide, but differs from cellulose in its properties. Chitin is highly hydrophobic and is insoluble in water and most
organic solvents. It is soluble in hexafluoroisopropanol, hexafluoroacetone, chloroalcohols
in conjugation with aqueous solutions of mineral acids [24] and dimethylacetamide containing
5% lithium chloride. Chitosan, the deacetylated
product of chitin, is soluble in dilute acids such
as acetic acid, formic acid, etc. Recently, the gel
forming ability of chitosan in N-methylmorpholine N-oxide and its application in controlled
drug release formulations has been reported
[3032]. The hydrolysis of chitin with concentrated acids under drastic conditions produces
relatively pure D-glucosamine.
The nitrogen content of chitin varies from 5
to 8% depending on the extent of deacetylation,
whereas the nitrogen in chitosan is mostly in the
form of primary aliphatic amino groups.
Chitosan, therefore, undergoes reactions typical
of amines, of which N-acylation and Schiff
reaction are the most important. Chitosan derivatives are easily obtained under mild conditions and can be considered as substituted
glucans.
N-Acylation with acid anhydrides or acyl
halides introduces amido groups at the chitosan
nitrogen. Acetic anhydride affords fully
acetylated chitins. Linear aliphatic N-acyl
groups above propionyl permit rapid acetylation
of hydroxyl groups. Higher benzoylated chitin is
soluble in benzyl alcohol, dimethylsulfoxide,
formic acid and dichloroacetic acid. The Nhexanoyl, N-decanoyl and N-dodecanoyl deriva-
tives have been obtained in methanesulfonic

acid [33,34].
At room temperature, chitosan forms aldimines and ketimines with aldehydes and
ketones, respectively. Reaction with ketoacids
followed by reaction with sodium borohydride
produces glucans carrying proteic and nonproteic amino groups. N-Carboxymethyl
chitosan is obtained from glyoxylic acid. Examples of non-proteic amine acid glucans derived
from chitosan are the N-carboxybenzyl
chitosans obtained from o- and p-phthalaldehydic acids [24,25]. Chitosan and simple
aldehydes produce N-alkyl chitosan upon hydrogenation. The presence of the more or less
bulky substituent weakens the hydrogen bonds
of chitosan; therefore N-alkyl chitosans swell in
water in spite of the hydrophobicity of the alkyl
chains, but they retain the film forming property
of chitosan [1].
4.1. Physical and chemical characterization

The structural details of cellulose, chitin and
chitosan are shown in Fig. 1. Cellulose is a
homopolymer, while chitin and chitosan are
heteropolymers. Neither random nor block
orientation is meant to be implied for chitin and
chitosan. The properties of chitin and chitosan
such as the origin of the material (discussed in
the previous section), the degree of N-deacetylation, molecular weight and solvent and solution
properties are discussed in brief. Glycol chitin, a
partially O-hydroxyethylated chitin, was the
first derivative of practical importance; other
derivatives and their proposed uses are shown in
Table 1.
4.1.1. Degree of N-acetylation

An important parameter to examine closely is
the degree of N-acetylation in chitin, i.e. the
ratio of 2-acetamido-2-deoxy-D-glucopyranose
to 2-amino-2-deoxy-D-glucopyranose structural
units. This ratio has a striking effect on chitin
solubility and solution properties. Chitosan is
the universally accepted non-toxic N-deacetylated derivative of chitin, where chitin is

N-deacetylated to such an extent that it becomes
soluble in dilute aqueous acetic and formic
acids. In chitin, the acetylated units prevail
(degree of acetylation typically 0.90). Chitosan
is the fully or partially N-deacetylated derivative
of chitin with a typical degree of acetylation of
less than 0.35. To define this ratio, attempts
have been made with many analytical tools
[3544], which include IR spectroscopy,
pyrolysis gas chromatography, gel permeation
chromatography and UV spectrophotometry,
first derivative of UV spectrophotometry, 1 HNMR spectroscopy, 13 C solid state NMR, thermal analysis, various titration schemes, acid
hydrolysis and HPLC, separation spectrometry
methods and, more recently, near-infrared spectroscopy [45].
4.1.2. Molecular weight

Chitosan molecular weight distributions have
been obtained using HPLC [46]. The weightaverage molecular weight (Mw ) of chitin and
chitosan has been determined by light scattering
[47]. Viscometry is a simple and rapid method
for the determination of molecular weight; the
constants a and K in the MarkHouwink
equation have been determined in 0.1 M acetic
acid and 0.2 M sodium chloride solution. The
intrinsic viscosity is expressed as
[h ] 5 KM a 5 1.81 3 10 23 M 0.93
The charged nature of chitosan in acid solvents
and chitosans propensity to form aggregation
complexes require care when applying these
constants. Furthermore, converting chitin into
chitosan lowers the molecular weight, changes
the degree of deacetylation, and thereby alters
the charge distribution, which in turn influences
the agglomeration. The weight-average molecular weight of chitin is 1.03310 6 to 2.5310 6 ,
but the N-deacetylation reaction reduces this to
1310 5 to 5310 5 [48].
Table 1
Chitin derivatives and their proposed uses
Derivative
Examples
Potential uses
N-Acyl chitosans
Formyl, acetyl, propionyl, butyryl, hexanoyl,

octanoyl, decanoyl, dodecanoyl, tetradecanoyl,
lauroyl, myristoyl, palmitoyl, stearoyl, benzoyl,
monochloroacetoyl, dichloroacetyl, trifluoroacetyl,
carbamoyl, succinyl, acetoxybenzoyl
Textiles, membranes
and medical aids
N-Carboxyalkyl
(aryl) chitosans
N-Carboxybenzyl, glycine-glucan (N-carboxymethyl chitosan), alanine glucan, phenylalanine

glucan, tyrosine glucan, serine glucan, glutamic
acid glucan, methionine glucan, leucine glucan
Chromatographic
media and metal
ion collection
N-Carboxyacyl
chitosans
From anhydrides such as maleic, itaconic, acetylthiosuccinic, glutaric, cyclohexane 1,2-dicarboxylic, phthalic, cis-tetrahydrophthalic, 5-norbornene-2,3-dicarboxylic, diphenic, salicylic, trimellitic, pyromellitic anhydride
o-Carboxyalkyl
chitosans
o-Carboxymethyl, crosslinked o-carboxymethyl
Molecular sieves,
viscosity builders,
and metal ion collection
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-ylchitosans, products obtained from ascorbic acid
Metal ion chelates
Palladium, copper, silver, iodine
Catalyst, photography,
health products, and
insecticides
Semisynthetic resins
of chitosan
Copolymer of chitosan with methyl methacrylate,

polyurea-urethane, poly(amideester), acrylamidemaleic anhydride
Textiles
Natural polysaccharide complexes,

miscellaneous
Chitosan glucans from various organisms
Flocculation and
metal ion chelation
Intermediate, serine
protease purification
Desalting filtration,
dialysis and insulating
papers
Enzymology, dialysis
and special papers
Enzyme
immobilization
Food additive and
anticholesterolemic
Alkyl chitin, benzyl chitin

Hydroxy butyl chitin, cyanoethyl chitosan
Hydroxy ethyl glycol chitosan

Glutaraldehyde chitosan
Linoelic acidchitosan complex
Uracylchitosan, theophylline chitosan, adeninechitosan, chitosan salts of acid polysaccharides,
chitosan streptomycin, 2-amido-2,6-diaminoheptanoic acid chitosan
4.1.3. Solvent and solution properties

Both cellulose and chitin are highly crystalline, intractable materials and only a limited
number of solvents are known which are applicable as reaction solvents. Chitin and chitosan
degrade before melting, which is typical for
polysaccharides with extensive hydrogen bonding. This makes it necessary to dissolve chitin
and chitosan in an appropriate solvent system to
impart functionality. For each solvent system,
polymer concentration, pH, counterion concentration and temperature effects on the solution
viscosity must be known. Comparative data
from solvent to solvent are not available. As a
general rule, the maximum amount of polymer
is dissolved in a given solvent towards a
homogeneous solution. Subsequently, the polymer is regenerated in the required form (discussed in the following sections). A coagulant is
required for polymer regeneration or solidification. The nature of the coagulant is also highly
dependent on the solvent and solution properties
as well as the polymer used [54,75].
5. Chitin and its derivatives in fibre
formation
5.1. Natural microfibriller arrangement

Chitin has been known to form microfibrillar
arrangements in living organisms. These fibrils
are usually embedded in a protein matrix and
have diameters from 2.5 to 2.8 nm. Crustacean
cuticles possess chitin microfibrils with diameters as large as 25 nm. The presence of microfibrils suggests that chitin has characteristics
which make it a good candidate for fibre
spinning. To spin chitin or chitosan fibres, the
raw polymer must be suitably redissolved after
removal of extraneous material such as calcium
carbonate and proteins, which encase the microfibrils.
5.2. Fibre formation in retrospection

Numerous methods of spinning chitin fibres
have been reported since Von Weimarn reported
the first solutions of chitin that could be formed

into a ropy-plastic state in 1926. He prepared
the solution using inorganic salts capable of
strong hydration [49], such as LiCNS,
Ca(CNS) 2 , CaI 2 , CaBr 2 , CaCl 2 , etc. After this
report, many solvent systems including organic
solvents and mixtures of inorganic salts and
organic solvents came into existence.
To help the dissolution of chitin, it was Ndeacetylated in 5% caustic soda at 608C for 14
days [50]. Another procedure for N-deacetylation was to place the chitin in an autoclave for 3
h at 1808C and 10 atm pressure. It was pointed
out that 6 to 10% of solids of N-deacetylated
chitin can be brought into acidic solution at
room temperature. Aqueous acetic acid was
found to be suitable for this purpose.
After passing the polymer solutions through a
filter press to remove impurities, fibres were
spun. Chemicals incompatible with chitin were
suggested as coagulants. The resultant fibres
were washed and dried under tension. The final
product fibres had a round- to heart-shaped
cross section with a tensile breaking load of 35
kg / mm 2 (345 Pa). The fibres possessed a dull
luster similar to natural silk, leading to the
suggestion that the N-deacetylated chitin fibres
would make good artificial hair. The collection
and recycling of chitin from small-scale consumers was also suggested. Clark and Smith
reported a procedure for producing fibres by
dissolution of chitin at 958C in presaturated
solutions of lithium thiocyanate (saturated 608C)
[51]. No tensile properties or solution concentrations were reported. However, X-ray analysis
showed a high degree of orientation. Solvent
removal was not successful even at 2008C.
Lithium iodide was implied to have behaved in
the same manner. A ratio of 5 mol lithium
thiocyanate per mole anhydroglucose unit was
found to exist. This is comparable to the
celluloselithium thiocyanate compound. Cellulose solubility and the role of solvate / salt
complexes have been reviewed in detail [52,53].
Recently, Rathke and Hudson published a review highlighting the ability of chitin and
chitosan as fibre and film formers [54].
5.3. Novel solvent spin systems

5.3.1. Halogenated solvent spin system
In 1975, Austin suggested organic solvents
containing acids for the direct dissolution of
chitin. Such a system was chloroethanol and
sulfuric acid. The precipitation of chitin in
fibrillar form in water, methanol, or aqueous
ammonium hydroxide was mentioned, but no
fibre tensile data were presented [55].
In 1975, Brine and Austin suggested trichloroacetic acid (TCA) as a chitin solvent.
Chitin was pulverized and two parts by weight
were added to 87 parts by weight of a solvent
mixture containing 40% TCA, 40% chloral
hydrate (US Department of Justice, Drug Enforcement Agency, class IV controlled substance), and 20% methylene chloride over a
period of 3045 min. A filament was extruded
from this solution using a hypodermic needle
and acetone as the coagulant. The filament was
then neutralized with potassium hydroxide
(KOH) in 2-propanol followed by washing in
deionized water. The filaments were then cold
drawn. Two tensile breaks were taken at 60%
relative humidity and room temperature. The
first was from a filament with a cross section of
0.0830.10 mm, yielding a tensile strength of 72
kg / mm 2 (710 Pa) and a breaking elongation of
13%. The second filament had a cross section of
0.01430.740 mm, indicating a collapsed core
structure. It had a tensile strength of 104 kg /
mm 2 (1026 Pa) and a breaking elongation of
44% [56]. Syringing a filament cannot be
interpreted as conclusive evidence for a possible
wet spinning process. While syringe extrusion
might indicate the selection of a coagulant, it
would be rather surprising to obtain meaningful
tensile data. Shear forces in a spinneret are
much greater than those experienced in a syringe tip.
Kifune and co-workers suggested dissolving
chitin in TCA and a chlorinated hydrocarbon
such as chloromethane, dichloromethane, and
1,1,2-trichloroethane. The TCA concentration
should be kept between 25 and 75%. A concentration range between 1 and 10% chitin was
suggested as well as dissolution below room

temperature. Fibres were extruded through a
spinneret of 0.04 and 0.06 mm diameter into an
acetone coagulation bath followed by a methanol bath. The tensile strength of dried filaments
was in the range of 1.67 to 3.1 g / d with an
elongation from 8.7 to 20.0%. The strength of
the fibres was improved by leaving them in a
0.5 g / l aqueous caustic soda solution for 1 h.
The resultant tensile strengths were 2.25 to 3.20
g / d with elongations of 19.2 to 27.3%, respectively [57]. Kifune and co-workers further suggested that these chitin filaments were suitable
as absorbable surgical suture [58]. However,
TCA is very corrosive and degrades the polymer molecular weight. The breaking elongations
suggest that the halogenated solvents act as
plasticizers.
Fuji Spinning Company dissolved chitosan in
a mixture of water and dichloroacetic acid
(DCA). The 6.44% chitosan acetate salt solution
viscosity was 410 poise. The dope was extruded
through a platinum nozzle (30 holes of 0.2 mm
diameter each) into basic CuCO 3 (NH 4 )OH
solution to form fibres. Denier and tensile
properties were not reported [59].
Tokura and co-workers used a combination of
formic acid (FA), DCA and diisopropyl ether as
a solvent system. Chitin was cycled several
times from 2208C to room temperature in FA,
followed by addition of a small amount of
DCA. Diisopropyl ether was then added to
reduce the solution viscosity to below 199 poise
and tensile properties were also reported [60]. It
is noteworthy that the wet strength drops to
below 0.50 g / d but that the elongation increases
to 13%.
A TCA / dichloromethane spin system is also
described by the Unitika Co. Three parts chitin
were dissolved in 50 parts TCA and 50 parts
dichloromethane. The defoamed dope was extruded into acetone before wind-up. The bobbins were neutralized with KOH, washed with
water, and dried. The fibres had a tensile
strength of 2 g / d and 0.520 denier [61].
Unitika Co. also used the TCA / chloral hydrate / dichloroethane solvent system for chitin.
Five parts were dissolved in 100 parts of a 4:4:2

TCA / chloral hydrate / dichloroethane solvent
mixture and extruded through a 0.06 mm nozzle
into acetone. The fibres were treated with
methanolic NaOH. The optimum fibres gave a
tenacity of 3.2 g / d with an elongation of 20%
[62]. Unitika Co. followed this up with another
patent using a 60:40 TCA / trichloroethylene
spin dope mixture. Tensile properties were
unavailable [63]. In 1983, Unitika Co. showed
that a dope consisting of three parts chitin, 50
parts TCA, and 50 parts dichloromethane could
be spun at a rate of 1.7 ml / min under 25
kg / cm 2 pressure into acetone to form filaments.
The extrusion die had holes of 0.07 mm diameter, indicating a jet velocity of 8.8 m / min and
a take-up of 5 m / min. The coagulation bath was
maintained at 188C. The filaments were washed
with acetone at 188C for 10 min, rewound at 4.5
m / min, then neutralized, washed and dried. The
multifilament product had a total denier of 150
with a tenacity of 2.65 g / d [63]. A similar
system using four parts chitin in the same
solvent but a 40-hole die of 0.08 mm diameter
each was also used. The jet velocity was 10.4
m / min into a 258C acetone bath. A rewinding at
7 m / min followed the first take-up roll at 5
m / min. The total denier was 175; however, no
tensile properties were reported [64].
Some of the halogenated solvent systems
attained dry tenacities of above 3 g / d; however,
the low wet tenacities were still undesirable.
Although the fibre characterization was much
better for these systems, the polymer characterization lacked molecular weight as well as
degree of N-acetylation formation. Solution
properties would be hard to obtain due to rapid
chitin degradation in these solvents. Although
anhydrous coagulation baths were used and
compared, fibres were neutralized in aqueous
media. A study in completely anhydrous systems would be of interest, since it may lead to
more densely consolidated fibres. The implementation of these spin systems represents a
problem due to the nature of the solvents. TCA
and DCA are corrosive and degrade the polymer
upon short exposures. Chlorohydrocarbons are

increasingly environmentally unacceptable solvents. Hexafluoro-2-propanol and hexafluoroacetone sesquihydrate are toxic. Formic acid can
act as a sensitizer.
5.3.2. AmideLiCl system

In 1978, Rutherford and Austin summarized
the problems encountered in finding a solvent
system for chitin [65]. Austin suggested N,Ndimethylacetamide (DMAc)5% LiCl or Nmethyl-2-pyrrolidone (NMP)5% LiCl as solvents for chitin. A solution of 5% w / v was
obtained within 2 h with these systems. A
filament was extruded from the solution using a
15-gauge needle into an acetone coagulation
bath. This was followed by more washing and
drawing in acetone. The final filament was
washed in deionized water. Tensile properties
were obtained at 60% R.H. and room temperature at an applied stress of 0.1 cm / min. The
resultant dry tensile strengths for different crab
and shrimp species ranged from 24 to 60 kg /
mm 2 (236592 Pa) [66].
Russian researchers spun chitin fibres out of
DMAc / NMP solutions containing 5% chitin
and 5% LiCl (based on chitin content). These
fibres were drawn in a 50:50 ethanol / ethylene
glycol bath, giving an average yield strength of
390 MPa with 3% elongation. An initial
modulus of 2 GPa was also reported. Scanning
electron microscopy showed fibres with a round
fibrillar cross section [67]. A follow-up study
showed a decrease in the elasticity modulus and
relative elongation with increase in the degree
of N-acetylation (1230%). From X-ray analysis, an increase in the amount of amorphous
regions was observed with increase in degree of
acetylation [68].
The amidelithium systems showed some of
the best dry tenacities, although they still lack
adequate wet tenacities. The low wet tenacities
are probably due to low crystallinity and poor
consolidation of the fibre. The fibres and spin
dopes were well characterized but the polymers
used to prepare these dopes were not. Some
coagulation studies were carried out but a clear

comparison could not be made. A problem with
this spin system is the removal and recovery of
lithium from the fibre. The lithium acts as a
Lewis acid by solvating the chitin amide group.
It is unclear if this can be completely reversed
through washing, once the fibres are formed.
5.3.3. Amine oxide /water system

Attempts have been made to develop a process for chitosan fibres by direct dissolution
using a novel solvent system, N-methylmorpholine oxide / water (NMMO / H 2 O), but no
interesting tensile data were obtained from these
preliminary investigations [69].
6. Applications
The interest in chitin originates from the
study of the behaviour and chemical characteristics of lysozyme, an enzyme present in human
body fluids [70]. A wide variety of medical
applications for chitin and chitin derivatives
have been reported over the last three decades
[7173]. 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 [74].
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 [54]. Fibres made
of chitin and chitosan are useful as absorbable sutures and wound-dressing materials
[58,75,76]. Chitin sutures resist attack in bile,
urine and pancreatic juice, which are problem
areas with other absorbable sutures [58]. 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 [70,77]. Their use
in the apparal industry, with a much larger
scope, could be a long-term possibility [78].
6.1. Photography
Chitosan has important applications in photography 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 penetrated from one layer to another of a film by
diffusion [70].
6.2. 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 permanent waving lotions and several derivatives have
also been reported as nail lacquers [78].
6.3. 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 [79].
Yannas et al. proposed a design for artificial
skin, applicable to long-term chronic use, focusing on a nonantigenic membrane, which performs as a biodegradable template for synthesis
of neodermal tissue [80]. It appears that
chitosan, having structural characteristics similar to glycosamino glycans, could be considered
for developing such substratum for skin replacement [8183].
6.3.1. Chitin- and chitosan-based dressings

Chitin and chitosan have many distinctive
biomedical properties. However, chitin-based
10
wound healing products are still at the early

stages of research [84].
Sparkes and Murray [85] developed a surgical dressing made of a chitosangelatin complex. The procedure involves dissolving the
chitosan in water in the presence of a suitable
acid, maintaining the pH of the solution at about
23, 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.
Nara et al. [86] patented a wound dressing
comprising a nonwoven fabric composed of
chitin fibres made by the wet spinning technique. In one of the examples, chitin powder
was ground to 100 mesh and treated in 1 M HCl
for 1 h at 48C. It was then heated to 908C where
it was treated for 3 h in a 0.3% NaOH solution
to remove calcium and protein in the chitin
powder, and rinsed repeatedly followed by
drying. The resultant chitin was dissolved in a
dimethylacetamide solution containing 7 wt%
lithium chloride to form a 7% dope. After
filtering and allowing defoaming to occur, the
dope was extruded through a nozzle of diameter
0.06 mm and 200 holes into butanol at 608C at a
rate of 2.2 g / min. The chitin was coagulated
and collected at a speed of 10 m / min. The
resultant strand was rinsed with water and dried
to obtain a filament of 0.74 dtex with a strength
of 2.8 g / den. The filaments were then cut into
staple fibres. Using poly(vinyl alcohol) as a
fibrous binder, nonwoven dressings were made.
Kifune et al. [87] developed a new wound
dressing, Beschitin W, composed of chitin nonwoven fabric which proved to be beneficial in
clinical practice. Kim and Min [88] have developed a wound-covering material from polyelectrolyte complexes of chitosan with sulfonated chitosan. It is proposed that wound healing
is accelerated by the oligomers of degraded

chitosan by tissue enzymes and this material
was found to be effective in regenerating the
skin tissue in the area of the wound.
Biagini et al. [89] developed an N-carboxybutyl chitosan dressing for treating plastic
surgery donor sites. A solution of N-carboxybutyl chitosan was dialyzed and freeze-dried to
produce a 1032030.5 cm 3 soft and flexible
pad, which was sterilized and applied to the
wound. This dressing could promote ordered
tissue regeneration compared to control donor
sites. Better histoarchitectural order, better vascularization and the absence of inflammatory
cells were observed at the dermal level, while
fewer aspects of proliferation of the malpighian
layer were reported at the epidermal level.
The British Textile Technology Group
(BTTG) patented a procedure for making a
chitin-based fibrous dressings [9093]. 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 Mucor 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 nonanimal 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.
Recently, Muzzarelli [94] introduced another

chitosan derivative,
5-methylpyrrolidinone
chitosan, which is believed to be very promising
in medical applications. This polymer is claimed
to be compatible with other polymer solutions,
including gelatin, poly(vinyl alcohol), poly(vinyl pyrrolidone) and hyaluronic acid. The
advantages include healing of wounded mensical tissues, and of decubitus ulcers, depression
of capsule formation around prostheses, limitation of scar formation and retraction during
healing. Some wound-dressing samples were
prepared from an aqueous solution of this 5methylpyrrolidone chitosan, which was dialyzed
and laminated between stainless steel plates and
freeze-dried to yield fleeces. The material could
be fabricated into many different forms, such as
filaments, nonwoven fabrics, etc. Once applied
to a wound, 5-methylpyrrolidinone chitosan
becomes available in the form of oligomers
produced under the action of lysozyme.
Another chitin derivative, dibutyrylchitin,
was prepared by treatment of krill chitin with
butyric anhydride in the presence of perchloric
acid as a catalyst at 25308C [95]. Samples of
polymers with molecular weights high enough
to form fibres were obtained and dibutyryl
chitin fibres were made by dry spinning a 20
22% solution into acetone. The fibres have
tensile properties similar to or better than those
of chitin. Moreover, it was claimed that chitin
fibres with good tensile properties could be
obtained by alkaline hydrolysis of dibutyryl
chitin fibres without destroying the fibre structure.
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.
6.4. 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
11
for digestion of milk lactose. Cows milk contains only a limited amount of the NAG moiety,
hence some infants fed cows milk may have
indigestion. Many animals and some humans
(including the elderly) have similar lactose
intolerances [96,97].
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 [98]. Chickens fed a commercial broiler diet containing 20% dried whey
and 2 or 0.5% chitin had significantly improved
weight again compared to controls [99,100].
The feed efficiency ratio shifted from 2.5 to
2.38 due to incorporation of chitin in the feed
[100].
6.5. Opthalmology
Chitosan possesses all the characteristics required for making an ideal contact lens: optical
clarity, mechanical stability, sufficient optical
correction, gas permeability, particularly towards 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 antimicrobial and wound healing properties of
chitosan along with an excellent film capability
make chitosan suitable for development of
ocular bandage lenses [101].
6.6. 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.
6.6.1. Metal capture from wastewater

Nair and Madhavan [102] used chitosan for
12
the removal of mercury from solutions, and the

adsorption kinetics of mercuric ions by chitosan
were reported by Peniche-covas et al. [103].
The results indicate that the efficiency of adsorption of Hg 21 by chitosan depends upon the
period of treatment, the particle size, initial
concentration of Hg 21 and quantity of chitosan.
Jha et al. [104] studied the adsorption of
Cd 21 on chitosan powder over the concentration
range of 110 ppm using various particle sizes
by adopting a similar procedure as for the
removal of mercury.
Hydroxymethyl chitin and other water-soluble derivatives are useful flocculents for anionic
waste streams. Chitosan N-benzylsulfonate derivatives were used as sorbents for removal of
metal ions in an acidic medium by Weltrowski
et al. [105]. The selective adsorption capacity
for metal ions of amidoximated chitosan beadg-PAN copolymer has been studied by Kang et
al. [106]. These investigations clearly indicate
that chitosan has a natural selectivity for heavy
metal ions and is useful for the treatment of
wastewater.
McKay et al. [107] used chitosan for the
21
21
21
21
removal of Cu , Hg , Ni and Zn within
the temperature range 25608C at near neutral
pH. Further adsorption parameters for the removal of these metal ions were reported by
Yang et al. [108]. Maruca et al. [109] used
chitosan flakes of 0.44 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. Pseudo-first-order kinetics are reported.
6.6.2. Colour removal from textile mill

effluents
6.6.2.1. Sorption of dyes
No single decolorization method is likely to
be the optimum for all wastewater streams
[110]. 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 naphthol 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 [111]. However, these
effects are small and normal wastewater temperature variations do not significantly affect the
overall decolorization performance [112]. Also,
the wastewater pH may be an important factor
in the sorption of certain dyes onto chitosan
because, at low pH, chitosans 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.
For almost all the treatment strategies, a
major factor which has not yet been adequately
characterized is the effect of typical wastewater
contaminants on decolorization efficiencies. In
typical dyeing systems it is well known that
certain additives such as salt and surfactants can
either accelerate or retard dye sorption processes. The extreme variability of textile wastewater must be taken into account in the design
of any decolorization system.
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 satura-
tion value beyond which further sorption is not

possible.
6.6.2.2. Dye-binding properties of chitin and

chitosan
Knorr examined the dye-binding properties
by weighing 0.5 or 2.0 g chitin or chitosan in
centrifuge tubes, adding 20 g of aqueous dye
solution (5 to 49 mg dye / l) and then shaking
the closed centrifuge tubes for 30 min at 200
rpm in a horizontal position. The samples were
then centrifuged for 35 min at 45003g, the
supernatant decanted and the water uptake of
chitin and chitosan determined after Sosulski
[113]. The absorbance of the supernatant was
measured at 505 nm using decolorized water as
a blank. The weight of the supernatant was used
as the basis for the calculation of the total
amount of dye bound or released. pH adjustment was carried out by using either 10 ml of a
commercial buffer solution or by adding 0.1 M
HCl to a slurry of 0.5 g chitin / chitosan and 10
ml of dye solution. After stirring for 15 min, the
pH was readjusted and deionized water added to
20.5 g total weight. Chitosan formed gels at pH
values below 5.5 and no dye-binding measurements could be obtained.
The effects of dye concentration and chitin /
chitosan dye solution ratios on dye-binding
capacity and water uptake of chitin and chitosan
are discussed in detail elsewhere [114]. Marked
differences between water uptake of chitin and
chitosan exist with chitosan taking more water
than chitin. The difference may be due to
differences in crystallinity of the products or
due to differences in the amount of salt-forming
groups [115]. Differences in the amount of
covalently bound protein residue might also
affect water uptake.
Dye concentrations had no marked effect on
the water uptake but correlated significantly
with the dye-binding capacity of chitin and
chitosan [116]. The effect of pH on the dyebinding capacity of chitin and chitosan was also
studied. A decline in the dye-binding capacity
above pH 7.0 was observed. Within the pH
13
range 2.07.0 the dye-binding capacity of chitin

was shown to be stable, while chitosan formed
gels below pH 5.5 and could not be evaluated.
6.7. Paper finishing

Chitosan has been reported to impart wet
strength to paper [117]. 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.
6.8. Solid-state batteries

Chitosan is insoluble in water. This poses a
problem in the fabrication of solid-state protonconducting 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 solidstate 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 [118].
6.9. 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. Controlled-
14
release 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 (Fig. 2)
[119].
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 [119132]. 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 [74] with gel-forming ability at low pH.
Moreover, chitosan has antacid and antiulcer
activities which prevent or weaken drug irrita-
Fig. 2. Controlled drug delivery versus immediate release.
tion in the stomach [133,134]. 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 [1,4,54,72,73,75,135,136].
6.9.1. 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
crosslinking, but also on the content and state of
the water in the hydrogel. Hydrogels have been
widely used in controlled-release systems
[137,138].
Recently, hydrogels which swell and contract
in response to external pH [139141] 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 [142]. It is
known that the release of drugs from hydrogels
depends on their structure or their chemical
properties in response to pH [143,144]. 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 [145]. Sometimes the polymers
used are biodegradable to obtain a desirable
device to control drug release [146]. 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. Some
recent advances in controlled-release formulations using gels of chitin and chitosan are
presented here.
6.9.1.1. Chitosan /polyether interpenetrating
polymer network ( IPN) hydrogel
Yao et al. [147] reported a procedure for the
preparation of semi-IPN hydrogel based on
glutaraldehyde-crosslinked chitosan with an interpenetrating polyether polymer network. The

pH sensitivity, swelling and release kinetics and
structural changes of the gel in different pH
solutions were studied [139,140,148,149]. The
physicochemical properties of the hydrogel depend not only on the molecular structure, the gel
structure and the degree of crosslinking, but also
on the content and state of the water in the
hydrogel. Since the inclusion of water significantly affects the performance of hydrogels, a
study of the physical state of water in the
hydrogels is of great importance to understand
the nature of interactions between absorbed
water and polymers. Yao et al. [149] studied the
dynamic water absorption characteristics, state
of water, correlation between state of water and
swelling kinetics of chitosanpolyether hydrogels by applying techniques such as DSC and
some novel techniques such as positron annihilation life-time spectroscopy.
Yao et al. [140] observed rapid hydrolysis of
the gel with decrease in the ionic strength, i.e. a
higher degree of swelling in lower ionic
strength solution [74]. The hydrolysis of the gel
can be controlled by the amount of crosslinker
applied. The more crosslinker added, the higher
the crosslink density of semi-IPNs, which results in a lower degree of swelling and slower
hydrolysis [140].
Chlorhexidini acetas and Cimetidine were
used as model drugs for drug release studies. A
fast swelling of gels results in higher drug
release at pH ,6 in comparison to that at pH
.6 [139,147].
6.9.1.2. Semi-IPN hydrogel polymer networks

of b -chitin and poly(ethylene glycol) macromer
Semi-IPN polymer network hydrogels composed of b-chitin and poly(ethylene glycol)
macromer were synthesized for biomedical applications [150,151]. The thermal and mechanical properties of these hydrogels have also been
studied. The tensile strengths of semi-IPNs in
the swollen state were found to be between 1.35
and 2.41 MPa, the highest reported values to
date for crosslinked hydrogels. They used these
15
hydrogels as wound-covering materials and also

studied the drug release behaviour using silver
sulfadiazine as a model drug [152].
6.9.1.3. Hydrogels of poly(ethylene glycol)-copoly( lactone) diacrylate macromers and b chitin

Lee and Kim [153] reported a procedure for
preparing poly(esteretherester) triblock copolymers. The synthesis of the triblock copolymers was carried out by bulk polymerization
using low toxic stannous octoate as catalyst or
without catalyst (Fig. 3). Investigations of the
thermal and mechanical properties were carried
out. Vitamin A, vitamin E and riboflavin were
used as model drugs [154,155]. However, there
were no reports on swelling kinetics and solubility parameters of the gels.
6.9.1.4. Hydrogels of poly(ethylene glycol)
macromer /b -chitosan
In their studies on chitosan for biomedical
applications, Lee et al. [156] reported a procedure for preparing semi-IPN polymer network
hydrogels composed of b-chitosan and poly(ethylene glycol) diacrylate macromer. The
hydrogels were prepared by dissolving a mixture of PEGM and b-chitosan in aqueous acetic
Fig. 3. Synthetic scheme of PEGLM or PEGCM / b-chitin semiIPNs.
16
acid. The resulting mixture was then cast to

films, followed by subsequent crosslinking with
2,2-dimethoxy-2-phenylacetophenone as nontoxic photo initiator by UV irradiation. They
studied the crystallinity and thermal and mechanical properties of the gels.
6.9.1.5. Hydrogels of chitosan /gelatin hybrid

polymer network
Yao et al. [157] reported a novel hydrogel
based on crosslinked chitosan / gelatin with a
glutaraldehyde hybrid polymer network. They
observed drastic swelling of the gels at acidic
pH in comparison to basic solutions.
Levamisole, cimetidine and chloramphenicol
were used as model drugs. A pH-dependent
release of cimetidine, levamisole and chloramphenicol from the gel was reported.
6.9.1.6. Chitosanamine oxide gel
Dutta et al. [3032] prepared an homogeneous chitosanamine oxide gel and studied its
swelling behavior and release characteristics in
a buffer solution (pH 7.4) at room temperature.
Homogenous erosion of the matrix and a near
zero-order release of ampicillin trihydrate were
observed. They reported the thermal properties
of the chitosanamine oxide gel in a further
study [31].
6.9.2. Chitin and chitosan tablets
Many direct-compression diluents have been
reported in the literature, but every diluent has
some disadvantages [158]. 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
[159,160].
6.9.2.1. Directly compressed tablets containing
chitin or chitosan in addition to lactose or
potato starch
Sawayanagi et al. [161] reported the fluidity
and compressibility of combined powders of
lactose with chitin (lactose / chitin), with
chitosan (lactose / chitosan) and potato starch

with chitin (potato starch / chitin), and with
chitosan (potato starch / chitosan). The disintegration properties of tablets made from these
powders, in comparison with those of combined
powders of lactose with MCC (lactose / MCC)
and potato starch with MCC (potato starch /
MCC) in order to develop new direct-compression diluents, are also reported [161]. The
fluidity of combined powders with chitin and
chitosan was greater than that of the powder
with crystalline cellulose. The reported hardness
of the tablets follows the order: chitosan
tablets.MCC.chitin. In disintegration studies,
tablets containing less than 70% chitin or
chitosan passed the test. Moreover, the ejection
force of the tablets of lactose / chitin and lactose / chitosan was significantly less than that of
lactose / crystalline cellulose tablets [161]. However, no reports are available on controlled drug
release formulations using these tablets.
6.9.2.2. Chitosan tablets for controlled release:

anioniccationic interpolymer complex
Recently, chitosan has gained importance as a
disintegration agent due to its strong ability to
absorb water. It has been observed that chitosan
contained in tablets at levels below 70% acts as
a disintegration agent [161,162]. Neau et al.
[163] investigated the sustained-release characteristics of ethylcellulose tablets containing
theophylline as the model drug. Several equations were tested to characterize release mechanisms with respect to the release data. The
investigations reveal that, at high drug loading,
drug was released by a diffusion mechanism
with a rate constant that increased with an
increase in aqueous solubility. At low drug
loading, polymer relaxation also becomes a
component of the release mechanism. However,
its contribution to drug release was less pronounced as drug solubility decreased, becoming
negligible in the case of theophylline.
Recently, Mi et al. [164] have reported
alginate as an anionic polyelectrolyte to control
the swelling and erosion rates of chitosan tablets
17
in acidic media. Investigations of the drug

release mechanism of various tablets have been
carried out based on Peppass model [165,166]
and nuclear magnetic resonance imaging microscopy was used to examine the swelling / diffusion mechanism of various tablets [164].
6.9.3. 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 microspheres 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. [167] 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.
6.9.3.1. Crosslinked chitosan microspheres
coated with polysaccharides or lipid
The preparation of crosslinked chitosan
microspheres coated with polysaccharide or
lipid for intelligent drug delivery systems has
been reported (Fig. 4) [167]. The microspheres
were prepared with an inverse emulsion of 5fluorouracil (5-FU) or its derivative solution of
hydrochloric acid of chitosan in toluene containing SPAN 80. Chitosan was crosslinked
through Schiffs salt formation by adding a
glutaraldehyde solution in toluene. At the same
time, the amino derivatives of 5-FU were
immobilized, obviously resulting in an increase
in the amount of drug within the microspheres.
The microspheres were coated with anionic
polysaccharides (e.g., carboxymethylchitin, etc.)
Fig. 4. Schematic structure of a chitosan gel microsphere coated

with anionic polysaccharide and lipid.
through a polyion complex formation reaction.

In the case of lipid-coated microspheres, the
microspheres along with dipalmitoyl phosphalidyl choline (DPPC) were dispersed in
chloroform. After evaporation of the solvent,
microspheres were obtained coated with a
DPPC lipid multilayer, which exhibited a transition temperature of a liquid crystal phase at
41.48C. The diameter range of the microspheres
was 250300 nm with a narrow distribution.
The stability of the dispersion was improved by
coating (Fig. 5) the microsphere with anionic
polysaccharide or a lipid multilayer.
A comparative study on the release of 5-FU
and its derivatives from a polysaccharide-coated
microsphere MS (CM) was carried out in
physiological saline at 378C. The data indicated
that the 5-FU release rate decreased in the
order: free 5-FU.carboxymethyl type 5-FU.
ester type 5-FU. The results revealed that the
coating layers on the microspheres were effective barriers to 5-FU release.
Lipid mutilayers with a homogeneous composition generally show a gelliquid crystal
transition. When the temperature is raised to
428C, which is higher than the phase transition
of 41.48C, the amount of 5-FU released increased, and the amount of drug delivered
decreased at 378C, which is lower than the
transition temperature. Due to the improved
recognition function of polysaccharide chains
for animal cell membranes, delivery systems
from polysaccharide-coated microspheres, MS
(CM), seem promising.
18
Moreover, the release rate can be controlled via

the composition of the HPN and the degree of
deacetylation of chitosan.
6.9.3.3. Chitosan microspheres for controlled

release of diclofenac sodium
Gohel et al. [169] reported on chitosan microspheres containing diclofenac sodium, which
were prepared by a coacervation phase separation method. Chitosan and glutaraldehyde
were used as coating material and crosslinking
agent, respectively. In vivo studies were performed on New Zealand white rabbits. Moreover, the microspheres were found to be stable
at 458C for 30 days. Students t test was
performed for the results of in vitro dissolution
data for fresh and aged samples (30 days at
458C) and no significant difference was found
upon storage.
Fig. 5. Preparation of MS (CM), MS (CML) and MS (CM)
polysaccharide. A schematic diagram.
6.9.3.2. Chitosan /gelatin network polymer

microspheres
In their studies on the pharmaceutical applications of chitin and chitosan, Yao and coworkers [168] reported chitosan / gelatin network polymer microspheres for controlled release of cimetidine. The drug-loaded microspheres were prepared by dissolving chitosan,
gelatin (1:1 by weight) and cimetidine in 5%
acetic acid. A certain amount of Tween-80 and
liquid paraffin at a water-to-oil ratio of 1:10 was
added to the chitosan / gelatin mixture under
agitation at 650 rpm at 308C. A suitable amount
of 25% aqueous glutaraldehyde was added to
the inverse emulsion and the system maintained
for 2 h. Finally, the liquid paraffin was vaporized under vacuum to obtain microspheres.
The drug release studies were performed in
hydrochloric acid solution (pH 1.0) and potassium dihydrogen phosphate (pH 7.8) buffer at
an ionic strength of 0.1 m / l. A pH-dependent
pulsed-release behavior of the hybrid polymer
network (HPN) matrix was observed [168].
6.9.3.4. Chitosanpolyethylene oxide

nanoparticles as protein carriers
Hydrophilic nanoparticulate carriers have
many potential applications for the administration of therapeutic molecules. The recently
developed hydrophobichydrophilic carriers require the use of organic solvents for their
preparation and have a limited protein-loading
capacity [170173]. To address these limitations, Calvo et al. [174] reported a new approach for the preparation of nanoparticles
made solely of hydrophilic polymer. The preparation technique, based on an ionic gelation
process, is extremely mild and involves a
mixture of two aqueous phases at room temperature (Fig. 6). One phase contains the
chitosan (CS) and a diblock copolymer of
ethylene oxide and sodium tripolyphosphate
(TPP). The size (2001000 nm) and zeta potential (between 120 and 160 mV) of the
nanoparticles can be modulated conventionally
by varying the CS / PEO-PPO ratio. Furthermore, using bovine serum albumin (BSA) as a
model protein, it was shown that these new
nanoparticles have great protein loading capacity (entrapment efficiency up to 80% of the
Fig. 6. The preparation of CS nanoparticles. A schematic diagram.
protein) and can provide continuous release of

the entrapped protein for up to 1 week.
6.9.3.5. Chitosan /calcium alginate beads

The encapsulation process of chitosan and
calcium alginate as applied to encapsulation of
haemoglobin was reported by Huguet et al.
[175]. In the first process, a mixture of haemoglobin and sodium alginate is added dropwise to
a solution of chitosan and the interior of the
capsules thus formed in the presence of CaCl 2 is
hardened. In the second method, the droplets
were directly pulled off in a chitosanCaCl 2
mixture. Both procedures lead to beads containing a high concentration of haemoglobin
(more than 90% of the initial concentration (150
g / l) is retained inside the beads) provided the
chitosan concentration is sufficient.
The molecular mass of chitosan (245 000 or
390 000 Da) and the pH (2, 4, or 5.4) had only
a slight effect on the entrapment of haemoglobin, the best retention being obtained with
beads prepared at pH 5.4. The release of
haemoglobin during bead storage in water was
found to be dependent on the molecular weight
of chitosan. The best retention during storage in
water was obtained with beads prepared with a
high molecular weight chitosan solution at pH
2.0. Considering the total loss in haemoglobin
during bead formation and after 1 month of
storage in water, the best results were obtained
by preparing the beads in an 8 g / l solution of
19
390 000 chitosan at pH 4 (less than 7% loss

with regard to the 150 g / l initial concentration).
Similarly, the encapsulation of various molecules [haemoglobin (Hb), bovine serum albumin
(BSA) and dextrans with various molecular
weights] in calcium alginate beads coated with
chitosan has been reported [176,177]. Their
release has been compared and the influence of
the dimensions, the chemical composition and
the molecular weight of the encapsulated materials have been analysed [176]. The ionic
interactions between alginate and chitosan at
different pH are depicted in Fig. 7.
6.9.3.6. Multiporous beads of chitosan

Several researchers [178,179] have studied
simple coacervation of chitosan in the production of chitosan beads. In general, chitosan is
dissolved in aqueous acetic acid or formic acid.
Using a compressed air nozzle, this solution is
blown into NaOH, NaOHmethanol, or ethylenediamine solution to form coacervate drops.
The drops are then filtered and washed with hot
and cold water successively. Varying the exclusion rate of the chitosan solution or the nozzle
diameter can control the diameter of the droplets. The porosity and strength of the beads
correspond to the concentration of the chitosan
acid solution, the degree of N-deacetylation of
chitosan, and the type and concentration of
coacervation agents used.
The chitosan beads described above have
been applied in various fields, viz. enzymatic
immobilization, chromatographic support, adsorbent of metal ions, or lipoprotein, and cell
cultures. It was confirmed that the porous
surfaces of the chitosan beads form a good cell
culture carrier. Hayashi and Ikada [180] immobilized protease onto porous chitosan beads
with a spacer and found that the immobilized
protease had higher pH, and thermal storage
stability, and exhibited higher activity towards
the small ester substrate N-benzyl-L-arginine
ethyl ester. In addition, Nishimura et al. [178]
investigated the possibilities of using chitosan
beads as a carrier for the cancer chemothera-
20
higher release rates at pH 12 than at pH

7.27.4. The effect of the amount of drug
loaded, the molecular weight of chitosan and the
crosslinking agent on the drug-delivery profiles
have been reported [181183].
Fig. 7. Schematic representation of the ionic interactions between

alginate and chitosan: (a) pH 5.4; (b) pH 2.0.
peutic adriamycin. Recently, Sharma et al.

[181183] prepared chitosan microbeads for
oral sustained delivery of nefedipine, ampicillin
and various steroids by adding these drugs to
chitosan and then entering a simple coacervation process. These coacervate beads can be
hardened by crosslinking with glutaraldehyde or
epoxychloropropane to produce microcapsules
containing rotundine [167]. The release profiles
of the drugs from all these chitosan delivery
systems were monitored and showed, in general,
6.9.4. Chitosan-based transdermal drug

delivery systems
Thacharodi and Rao [184186] reported permeation-controlled transdermal drug delivery
systems (TDS) using chitosan. Studies on propranolol hydrochloride (prop-HCl) delivery systems using various chitosan membranes with
different crosslink densities as drug release
controlling membranes and chitosan gel as the
drug reservoir have been performed. The
physicochemical properties of the membranes
have been characterized and the permeability
characteristics of these membranes to both
lipophilic and hydrophilic drugs have been
reported [184,185]. In vitro evaluations of the
TDS devices while supported on rabbit pinna
skin were carried out in modified Franz diffusion cells [186]. The in vitro drug release
profiles showed that all devices released propHCl in a reliable, reproducible manner. The
drug release was significantly reduced when
crosslinked chitosan membranes were used to
regulate drug release in the devices. Moreover,
the drug release rate was found to depend on the
crosslink density within the membranes. It was
observed that the device constructed with a
chitosan membrane with a high crosslink density released the minimum amount of drug. This
is due to the decreased permeability coefficient
of crosslinked membranes resulting from the
crosslink points.
6.10. Biotechnology
6.10.1. 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.
6.10.2. Cell-stimulating materials

6.10.2.1. In plants
Mainly two kinds of extracellular chitinase
were found in the normal cell suspension culture of rice (Oryza sativa L. var. japonica cv.
Koshihikari). In the presence of a chitin oligosaccharide mixture (degree of polymerization
28), however, the extracellular chitinase activity increased about three-fold over the control on
secreting an additional extracellular new chitinase isoform. These three chitinase isoforms are
one group of pathogenesis-related (PR) proteins
in plants [187].
Soyabeans 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 1.52.0-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 1012% over the control [188].
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 [187].
6.10.2.2. In animals
Extracellular lysozyme activity was enhanced
in in vitro cultures of several mammalian cells
by treatment with chitin and its derivatives. As a
result, connective tissue formation was stimu-
21
lated, and the self-defence 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.
6.10.3. 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,
Alternaria and Helminthosporium. The cationic
amino groups of chitosan probably bind to
anionic groups of these microorganisms, resulting in growth inhibition [189].
6.10.4. Blood anti-coagulants ( heparinoids)
Chitin and chitosan sulphates have blood
anticoagulant and lipoprotein lipase (LPL)-releasing activities. Chitin 3,6-sulfate showed
about two-fold anticoagulant activity and 0.1fold LPL-releasing activity over those of
heparin; the sulfate derivatives might be usable
as heparinoids for artificial blood dialysis [187].
6.10.5. 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 Noctanoylchitosan fibres are used as anti-thrombogenic materials [190].
6.11. 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. Its 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
22
improving muscle tone, metabolism and health.

Many supplements can help in the fat reduction
process, including pyruvate and chitosan. Pyruvate, 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. Chitosan fibre differs from other fibres in
that it possesses a positive ionic charge, which
gives it the ability to bond chemically with the
negatively charged lipids, fats and bile acids
[191193].
7. Conclusion
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 controlledrelease 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 excipient 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.
Acknowledgements
The author thanks Dr K.G. Ramachandran
Nair, Central Institute of Fisheries Technology,
Kochi, India, for providing the sample of

chitosan. The author is grateful to the Council
of Scientific and Industrial Research (CSIR),
Ministry of Human Resource Development
Groups, Govt. of India, New Delhi, for financial
assistance to carry out this research. The author
is indebted to the referees for a thorough
revision of the manuscript.
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Reactive & Functional Polymers 46 (2000) 127

www.elsevier.com / locate / react

A review of chitin and chitosan applications q

position C-2 replaced by an acetamido group.

M.N.V. Ravi Kumar / Reactive & Functional Polymers 46 (2000) 1 27

radability, non-toxicity, adsorption properties,

2. Processing of chitin and chitosan

Fig. 1. Structures of cellulose, chitin and chitosan.

chitin, chitosan and their derivatives. However,

Chitin is easily obtained from crab or shrimp

M.N.V. Ravi Kumar / Reactive & Functional Polymers 46 (2000) 1 27

tion, some soluble glycans are removed [24].

4. Properties of chitin and chitosan

M.N.V. Ravi Kumar / Reactive & Functional Polymers 46 (2000) 1 27

tives have been obtained in methanesulfonic

4.1. Physical and chemical characterization

4.1.1. Degree of N-acetylation

the universally accepted non-toxic N-deacetylated derivative of chitin, where chitin is

4.1.2. Molecular weight

M.N.V. Ravi Kumar / Reactive & Functional Polymers 46 (2000) 1 27

Formyl, acetyl, propionyl, butyryl, hexanoyl,

N-Carboxybenzyl, glycine-glucan (N-carboxymethyl chitosan), alanine glucan, phenylalanine

o-Carboxymethyl, crosslinked o-carboxymethyl

Metal ion chelates

Palladium, copper, silver, iodine

Copolymer of chitosan with methyl methacrylate,

Natural polysaccharide complexes,

Chitosan glucans from various organisms

Alkyl chitin, benzyl chitin

Hydroxy ethyl glycol chitosan

M.N.V. Ravi Kumar / Reactive & Functional Polymers 46 (2000) 1 27

4.1.3. Solvent and solution properties

5.1. Natural microfibriller arrangement

5.2. Fibre formation in retrospection

the first solutions of chitin that could be formed

M.N.V. Ravi Kumar / Reactive & Functional Polymers 46 (2000) 1 27

5.3. Novel solvent spin systems

suggested as well as dissolution below room

M.N.V. Ravi Kumar / Reactive & Functional Polymers 46 (2000) 1 27

Five parts were dissolved in 100 parts of a 4:4:2

upon short exposures. Chlorohydrocarbons are

5.3.2. AmideLiCl system

M.N.V. Ravi Kumar / Reactive & Functional Polymers 46 (2000) 1 27

coagulation studies were carried out but a clear

5.3.3. Amine oxide /water system

6.3. Chitosan as an artificial skin

6.3.1. Chitin- and chitosan-based dressings

M.N.V. Ravi Kumar / Reactive & Functional Polymers 46 (2000) 1 27

wound healing products are still at the early

is accelerated by the oligomers of degraded

M.N.V. Ravi Kumar / Reactive & Functional Polymers 46 (2000) 1 27

Recently, Muzzarelli [94] introduced another

6.4. Food and nutrition

6.6. Water engineering

6.6.1. Metal capture from wastewater

M.N.V. Ravi Kumar / Reactive & Functional Polymers 46 (2000) 1 27

the removal of mercury from solutions, and the

6.6.2. Colour removal from textile mill

[110]. Due to its unique molecular structure,

M.N.V. Ravi Kumar / Reactive & Functional Polymers 46 (2000) 1 27

tion value beyond which further sorption is not

6.6.2.2. Dye-binding properties of chitin and

range 2.07.0 the dye-binding capacity of chitin

6.7. Paper finishing