Journal of Scientific & Industrial Research Vol.

63, January 2004, pp 20-3

!hitin and chitosan" !he#istry, properties and applications

$radip %u#ar &utta', Joydeep &utta and V S (ripathi
) )

&epart#ent of !he#istry, *otilal +ehru +ational Institute of (echnolo,y, -llaha.ad 2

004

!hitin and chitosan are considera.ly /ersatile and pro#isin, .io#aterials. (he deacetylated chitin deri/ati/e, chitosan is #ore useful and interestin, .ioacti/e poly#er. &espite its .iode,rada.ility, it has #any reacti/e a#ino side ,roups, 0hich offer possi.ilities of che#ical #odifications, for#ation of a lar,e /ariety of useful deri/ati/es that are co##ercially a/aila.le or can .e #ade a/aila.le /ia ,raft reactions and ionic interactions. (his study loo1s at the conte#porary research in chitin and chitosan to0ards applications in /arious industrial and .io#edical fields. Keywords" !hitin, 2iode,rada.ility, !hitosan, 2io#aterials

Introduction !hitin is the second #ost u.i3uitous natural polysaccharide after cellulose on earth and is co#posed of 4 45-lin1ed 2-aceta#ido-2-deo6y- D-,lucose 4N-acetyl,lucosa#ine5 47i,ure 5. It is often considered as cellulose deri/ati/e, e/en thou,h it does not occur in or,anis#s producin, cellulose. It is structurally identical to cellulose, .ut it has aceta#ide ,roups 4 +8!9!835 at the !-2 positions. Si#ilarly the principle deri/ati/e of chitin, chitosan is a linear poly#er of 4 45-lin1ed 2-a#ino-2-deo6y -&-,lucopyranose and is easily deri/ed .y Ndeacetylation, to a /aryin, e6tent that is characteri:ed .y the de,ree of deacetylation, and is conse3uently a copoly#er of N-acetyl,lucosa#ine and ,lucosa#ine 47i,ure 25. !hitin is esti#ated to .e produced annually al#ost as #uch as cellulose. It has .eco#e of ,reat interest not only as an under-utili:ed resource .ut also as a ne0 functional .io#aterial of hi,h potential in /arious fields and the recent pro,ress in chitin che#istry is 3uite si,nificant.
!83 8 !8298 8 89 8+ 8 ! !83 9 8 8 9 8 9 89 8 8+ 8 !8298 8 9 !9 8
OH O O NH2 HO O OH O HO

xl

NHAc

7i,ure 2 C $artially deacetylated chitin

7i,ure C Structure of chitin ?????????? ' !orrespondence author ) =ni/ersity of -llaha.ad, -llaha.ad 2 e-#ail " p1d?43@Ayahoo.co#BR

002

!hitin is a 0hite, hard, inelastic, nitro,enous polysaccharide found in the e6os1eleton as 0ell as in the internal structure of in/erte.rates. (he 0aste of these natural poly#ers is a #a;or source of surface pollution in coastal areas. (he production of chitosan fro# crustacean shells o.tained as a food industry 0aste is econo#ically feasi.le, especially if it includes the reco/ery of carotenoids. (he shells contain considera.le 3uantities of asta6anthin, a caroteniod that has so far not .een synthesi:ed, and 0hich is #ar1eted as a fish food additi/e in a3uaculture, especially for sal#on. (he chitinous solid 0aste fraction of a/era,e Indian landin, of shellfish 0as ran,ed fro# 60,000 to <0,000 t. (he three parts of our #otherland, India, are surrounded .y ocean and its inner land is also /ery #uch rich 0ith ponds, la1es, and la,ons. (he proper utili:ation of those 0ater resources 4a3uaculture5 in ter#s of research in chitin and chitosan can .rin, the econo#ic and acade#ic prosperity of the nation. !hitin and chitosan are no0 produced co##ercially in India, $oland, Japan, the =S, +or0ay and -ustralia. considera.le a#ount of research is in pro,ress on chitin>chitosan 0orldo/er, includin, India, to tailor and i#part the re3uired functionalities to #a6i#i:e its utility.

&=((- et al." !8I(I+ & !8I(9S-+

!hitin and chitosan the naturally a.undant and rene0a.le poly#ers ha/e e6cellent properties such as, .iode,rada.ility, .io-co#pati.ility, non-to6icity, and 2 adsorption . (he reaction of chitosan is considera.ly #ore /ersatile than cellulose due to the presence of +82 ,roups. Various efforts ha/e .een #ade to prepare functional deri/ati/es of chitosan .y che#ical 3 #odifications , ,raft reactions, ionic interactions, and only fe0 of the# are found to dissol/e in 4 con/entional or,anic sol/ents . !hitosan is only solu.le in a3ueous solutions of so#e acids, and so#e 3,D 4,6 selecti/e N-al1ylidinations and N-acylation ha/e @ also .een atte#pted. -lthou,h se/eral 0ater-solu.le 2 or hi,hly s0ellin, deri/ati/es are o.tained, it is difficult to de/elop the solu.ility in co##on or,anic sol/ents .y these #ethods. *odification of the che#ical structure of chitin and chitosan to i#pro/e the solu.ility in con/entional or,anic sol/ents has <- 3 .een re/ie0ed .y #any authors . 9n the other hand, only a fe0 re/ie0s ha/e .een reported on 4- 6 .io#edical applications of chitin>chitosan , and no co#prehensi/e re/ie0 has yet .een pu.lished co/erin, the entire ran,e of applications. (he present re/ie0 co/ers the literature fro# EE3 to 2003 dealin, 0ith properties, processin,, and applications in /arious industrial and .io#edical fields. Chitin and Chitosan Processing !hitin and chitosan are natural resources 0aitin, for a #ar1et. (hey 0ere 0aste products of the cra.in, and shri#p cannin, industry. (he =S &epart#ent of !o##erce reported in E@3 that they 0ere o/er ,D0,000 *t of chitin produced as processin, 0aste fro# shellfish, 1rill, cla#s, oysters, s3uid, and fun,i. !o##ercially chitin and chitosan are of ,reat i#portance o0in, to their relati/ely hi,h percenta,e of nitro,en 46.<E per cent5 co#pared to synthetically su.stituted cellulose. (he crustacean shells #ainly in/ol/es the re#o/al of proteins and the dissolution of calciu# car.onate that is present in cra. shells in hi,h concentrations. (he resultin, chitin is deacetylated in 40 per cent sodiu# hydro6ide at 20 ! for -3 h. (his treat#ent produces @0 per cent deacetylated chitosan. (he follo0in, four steps in chronolo,ical order of the process are needed to produce chitosan fro# crustacean shells" 4i5 &eproteini:ation, 4ii5 &e#inerali:ation 4=npu.lished data, one of the authors, $radeep %u#ar &utta in/esti,ated a ne0 #ethod of de#inerali:ation of crustacean shells and clai#ed

.etter property than the e6istin, process5, 4iii5 &ecolouration, and 4i/5 &eacetylation.

!rustacean shells Si:e reduction $rotein separation 4+a985 Fashin, &e#inerali:ation 48!l5 Fashin, and &e0aterin, &ecolouration !hitin &eacetylation 4+a985 Fashin, and &e0aterin, !hitosan Properties of Chitin and Chitosan *ost of the naturally occurrin, polysaccharides e.,., cellulose, de6trin, pectin, al,inic acid, a,ar, a,arose, and carra,enas are natural and acidic in nature, 0hereas chitin and chitosan are e6a#ples of hi,hly .asic polysaccharides. (heir properties include solu.ility in /arious #edia, solution, /iscosity, polyelectrolyte .eha/ior, polyo6ysalt for#ation, a.ility to for# fil#s, #etal chelations, optical, and @ structural characteristics . -lthou,h the 4 45-anhydro,lucosidic .ond of chitin is also present in cellulose the characteristic properties of chitin>chitosan are not shared .y < cellulose . !hitin is hi,hly hydropho.ic and is insolu.le in 0ater and #ost or,anic sol/ents. It is solu.le in he6afluoroisopropanol, he6afluoroacetone, and chloroalcohols in con;unction 0ith a3ueous solutions of #ineral acids and di#ethylaceta#ide 4&*-c5 containin, D per cent lithiu# chloride E 4Bi!l5 . Recently the dissolution of chitosan in N#ethyl #orpholine-N-o6ide 4+**95>8 9 2 has .een 20,2 reported .y &utta et al. . (he hydrolysis of chitin 0ith concentrated acids under drastic conditions produces relati/ely the pure a#ino su,ar, &,lucosa#ine. &ependin, on the e6tent of deacetylation, chitin contains D to < per cent 40>/5 nitro,en, 0hich is #ostly in the for# of pri#ary aliphatic a#ino ,roups as found in chitosan. !hitosan under,oes the reactions typical of a#ines, of 0hich N-acylation and Schiff reactions are the #ost i#portant. !hitosan ,lucans are easily o.tained under #ild conditions .ut it is difficult to o.tain cellulose ,lucans.

22

J S!I I+& RGS V9B 63 J-+=-RH 2004

N-acylation 0ith acid anhydrides or acyl halides introduces a#ido ,roups at the chitosan nitro,en. -cetic anhydride affords fully acetylated chitins. Binear aliphatic N-acyl ,roups hi,her than propionyl per#it rapid acetylation of the hydro6yl ,roups in D,6 chitosan . 8i,hly .en:oylated chitin is solu.le in .en:yl alcohol, di#ethyl sulpho6ide 4&*S95, for#ic acid, and dichloroacetic acid. (he N-he6anoyl, Ndecanoyl and N-dodecanoyl deri/ati/es ha/e .een o.tained in #ethanesulphonic acid . !hitosan for#s aldi#ines and 1eti#ines 0ith aldehydes and 1etones, respecti/ely, at roo# te#perature. Reaction 0ith 1etoacids follo0ed .y reduction 0ith sodiu# .orohydride produces ,lucans carryin, proteic and non-proteic a#ino acid ,roups. N-car.o6y-#ethyl chitosan is o.tained fro# ,lyo6ylic acid. G6a#ples of non-proteic a#ino acid ,lucans deri/ed fro# chitosan are the N-car.o6y.en:yl chitosans o.tained fro# o- and p-phthalaldehydic 22 acids . !hitosan and si#ple aldehydes produce N-al1yl chitosan upon hydro,enation. (he presence of the #ore or less .ul1y su.stituent 0ea1ens the hydro,en .onds of chitosanI therefore, N-al1yl chitosans s0ell in 0ater inspite of the hydropho.icity of al1yl chains. ,3 (hey retain the fil# for#in, property of chitosan . !hitosan is #ore /ersatile in co#parision to chtin due to the presence of a#ino ,roups at the !-2 positions. Chemical Properties of Chitosan (he che#ical properties of chitosan are as follo0s" Binear poly#ine, Reacti/e a#ino ,roups, Reacti/e hydro6yl ,roups a/aila.le, !helates #any transitional #etal ions. Biological Properties of Chitosan 7ollo0in, are the .iolo,ical properties of chitosan" 2ioco#pati.le - +atural poly#er, - 2iode,rada.le to nor#al .ody constituents, - Safe and non-to6ic, 4the research in chitinase is note0orthy in this respect5. 2inds to #a##alian and #icro.ial cells a,,resi/ely,

Re,enerati/e effect on connecti/e ,u# tissue, -cclerates the for#ation of osteo.last responsi.le for .one for#ation, 8e#ostatic, 7un,istatic, Sper#icidal, -ntitu#or, -nticholestere#ic, -ccelerates .one for#ation, !entral ner/ous syste# depressant, I##unoad;u/ant.

Derivatives of Chitin and Chitosan !hitosan #ay .e readily deri/ati:ed .y utili:in, the reacti/ity of the pri#ary a#ino ,roup and the pri#ary and secondary hydro6yl ,roups. Jlycol chitin, a partially o-hydro6yethylated chitin 0as the 4,23 first deri/ati/e of practical i#portance . &eri/ati/es of chitin #ay .e classified into t0o cate,oriesI in each case, the N-acetyl ,roups are re#o/ed, and the e6posed a#ino function then reacts either 0ith acyl chlorides or anhydrides to ,i/e the ,roup +8!9R or is #odified .y reducti/e a#ination to +8!8 2!998 of ,reatest potential i#portance are deri/ati/es of .oth types for#ed .y reaction 0ith .ior polyfunctional rea,ents, thus carryin, sites for 24,2D further che#ical reaction . In practice, such reactions are carried out on nati/e chitin or on inco#pletely deacetylated chitin, chitosan, so that the resultin, poly#er contains three types of #ono#eric units. (hese polya#pholytes are particularly effecti/e in re#o/in, #etal cations fro# dilute solutions. !hitosan itself chelates #etal ions, especially those of transition #etals, and also finds application as a 26 #atri6 for i##o.ili:ation of en:y#es . Special attention has .een ,i/en to the che#ical #odification of chitin, since it has the ,reatest potential to .e fully e6ploited. Reactions 0ith pure chitin ha/e .een carried out #ostly in the solid state o0in, to the lac1 of solu.ility in ordinary sol/ents. - D0 per cent deacetylated chitin has .een found to .e solu.le in , @ 0ater . (his 0ater-solu.le for# of chitin is a useful startin, #aterial for its s#ooth #odifications, throu,h /arious reactions in solution phase. So#e of the /ery recently reported chitosan deri/ati/es are enu#erated as follo0s"

&=((- et al." !8I(I+ & !8I(9S-+

23

(i) N-phthaloylation of Chitosan

22

90in, to its poor solu.ility in so#e li#ited or,anic sol/ents, it needs so#e che#ical #odifications. N-phthaloylation of chitosan 0as e6pected to .e effecti/e for solu.ili:ation since it affi6es a .ul1y ,roup to the ri,id .ac1.one and .rea1s hydro,en ato#s on the a#ino ,roups to pre/ent hydro,en .ondin,. 7ully deacetylated chitosan 0as treated 0ith phthalic anhydride in &*7 to ,i/e Nphthaloyl-chitosan. It 0as readily solu.le in polar or,anic sol/ents. 7urther reactions had .een carried out usin, this ne0 deri/ati/e to i#pro/e the solu.ility of chitosan. (hose are ,i/en .elo0 for .etter understandin,.
O O
OH HO NH2 O O
n

catalysts. (hey de#onstrated that a stron,er interaction e6isted .et0een 0ater and chitosan chains after ,raftin, lactic and>or ,lycolic acid. (he side chains could a,,re,ate and for# physical crosslin1in,, 0hich results in p8-sensiti/e chitosan E,30-33 hydro,els . (hese hydro,els are considered potentially useful for .io#edical applications such as, 0ound dressin,s and dru, deli/ery syste#s, since .oth polyester side chains and chitosan are 34 .ioco#pati.le and .iode,rada.le .
(v) Cd' (uantum dots ((Ds) Chitosan Biocomposite
)*

O
HO

OH O O

TrCl
HO
n

OTr O O NPhTh
n

O 1)Ac2OAc 2 2) CHClCO 2 H
AcO

OH O O NPhTh
n

(Me3Si)2NH Me3SiCl
AcO

OSiMe3 O O NPhTh
n

&eri/ati/es 0ith !dS K&s i#pro/ed a3ueous solu.ility and sta.ility of chitosan. (hey also influenced the ther#al deco#position of chitosan. In the presence of this ther#al deco#position of o chitosan 0as shifted to D0 !. -n efficient procedure for the preparation of !dS K&s chitosan .ioco#posite is achie/ed .y #i6in, chitosan 0ith !d4-c5 2 and su.se3uently dissol/in, in per cent 8-c a3ueous solution, follo0ed .y the treat#ent 0ith !dS and thus s#ooth, flat, yello0 !dS K&s chitosan co#posite fil#s 0ere o.tained.
(vi) Chitosan-gadopentetic !cid Comple+ ,anoparticles for Cancer -herapy

-ll these deri/ati/es are solu.le in co##on polar or,anic sol/ents.

(ii) Dendroni ed Chitosan-sialic !cid "y#rids

(o i#pro/e 0ate-solu.ility, Sashi0a et al. has successfully synthesi:ed dendroni:ed chitosan-sialic acid hy.rids .y usin, ,allic acid as focal point and tri4ethylene ,lycol5 as spacer ar#. (he 0ater solu.ility of these no/el deri/ati/es 0as further i#pro/ed .y N-succinylation of the re#ainin, a#ine functionality.
(iii) $ethylthiocar#amoyl and Phenylthiocar#amoyl Chitosans

2@

Recently, 2a.a et al. ha/e synthesi:ed #ethylthiocar.a#oyl and phenylthiocar.a#oyl chitosan deri/ati/es to e6a#ine the selecti/ity to0ard #etal ions fro# a3ueous a##oniu# nitrate solution.
CH2OH HO O O

2<

(he potential of ,adoliniu# neutran capture 36, 3@ therapy has .een reported in the recent past . In 3< EEE, (o1u#itsu et al. ha/e reported that chitosan,adopentetic acid co#ple6 nanoparticles could .e used for ,adoliniu# neutran capture therapy 4Jd+!(5. It is a cancer therapy that utili:es protons and neutrans and electrons e#itted in vivo as a result of the neuclear neutran capture reaction 0ith 3< ad#inistered ,adoloniu#- D@, a non-radio ele#ent . 3E (o1u#itsu et al. ha/e de#onstrated that Jd-+!( usin, no/el ,adoliniu#-loaded nanoparticles are potentially hi,hly suita.le for intratu#oral in;ection into solid tu#or.
(vii) ,anocomposite from ,atural Polysaccharide (Chitin&chitosan)

R=

CH3

MTC

PTC
n

HNCNHR S

(iv) %actic&glycolic !cid-chitosan "ydrogels

(he synthesis of chitosan hydro,els 0as carried 2E out .y Ku et al. .y direct ,raftin, of &,B-lactic and>or ,lycolic acid onto chitosan in the a.sence of

-lthou,h chitin and chitosan are useful .io#ass poly#ers, their applications are li#ited. -n outstandin, concept 0ould .rin, a re/olution .y #i6in, natural poly#ers 0ith #an #ade poly#ers 4synthetic poly#ers5. Institute for *arine Resource 40,4 and Gn/iron#ent, Japan studied #echanoche#ical preparation of a no/el co#posite under a dry and solid state. (hey synthesi:ed a ne0 type of polysaccharide co#posite .y .all-#illin, a polysaccharide 0ith synthetic poly#er. (he ther#al

24

J S!I I+& RGS V9B 63 J-+=-RH 2004

.eha/iour and #olecular #otion of the synthetic poly#er in the co#posite are entirely different fro# those of ori,inal one. (hese results su,,est stron, interactions .et0een a polysaccharides and synthetic poly#er and thus co#pati.ili:ation of the polysaccharides and synthetic poly#er. (he authorsL la.oratory synthesi:ed chitosan-polylactic acid .ased nanoco#posites under #ild conditions for s#art dru, release 4=npu.lished results5. !pplications of Chitin and Chitosan (he interest in chitin ori,inates fro# the study of the .eha/iour and che#ical characteristics of lyso:y#e, an en:y#e present in the hu#an .ody fluids. It dissol/es certain .acteria .y clea/in, the @ chitinous #aterial of the cell 0alls . - 0ide /ariety of #edical applications for chitin and chitin deri/ati/es ha/e .een reported o/er the last three 42,43 decades . It has .een su,,ested that chitosan #ay .e used to inhi.it fi.roplasia in 0ound healin, and to pro#ote tissue ,ro0th and differentiation in tissue 44 culture . (he poor solu.ility of chitin is the #a;or li#itin, factor in its utili:ation and in/esti,ation of its properties and structure. &espite these li#itations, /arious applications of chitin and #odified chitins ha/e .een reported in the literature, e.,., as ra0 ,4D,46 #aterial for #an-#ade fi.res . 7i.res #ade of chitin and chitosan are useful as a.sor.a.le sutures 2, @,44 and 0ound-dressin, #aterials . (hese chitin sutures resist attac1 in .ile, urine and pancreatic ;uice, 0hich are difficult 0ith other a.sor.a.le sutures. It has .een clai#ed that 0ound dressin,s #ade of chitin 44 and chitosan fi.res accelerate the healin, of 0ounds .y a.out @D per cent. -part fro# their applications in the #edical field, chitin and chitosan fi.ers ha/e potential applications in 0aste0ater treat#ent, 0here the re#o/al of hea/y #etal ions .y chitosan throu,h <,46,4@ chelation has recei/ed #uch attention . (heir use in the apparel industry, 0ith a #uch lar,er scope, 4<-D0 could .e a lon,-ter# possi.ility . Industrial !pplications of Chitosan &ue to its physical and che#ical properties, chitosan is .ein, used in a /ast array of 0idely different products and applications, ran,in, fro# phar#aceutical and cos#etic products to 0ater treat#ent and plant protection. In different applications, different properties of chitosan are re3uired. (hese properties chan,e 0ith, e.,., de,ree of acetylation and #olecular 0ei,ht as 0ell.

Cosmetics

*.

=sually or,anic acids are used as ,ood sol/ents for cos#etic applications. - natural a#inopolysaccharide, chitosan can .e enco#passed in the class of hydrocolloids. 8o0e/er, unli1e the #ost of other hydrocolloids 0hich are polyanions chitosan is the only natural cationic ,u# that .eco#es /iscous on .ein, neutrali:ed 0ith acid. It facilitates its interaction 0ith co##on inte,u#ents 4s1in co/ers5 and hair. !hitin and chitosan are fun,icidal and fun,istatic in nature. !hitosan is co#pati.le 0ith lots of .iolo,ically acti/e co#ponents incorporated in cos#etic products co#position. !hitosan or chitosanal,inate co#posites in the ran,e of - 0 , as 0ell as #icrocapsules includin, /arious hydropho.ic su.stances find a 0ide application in cos#etics. It #ay .e noted that su.stances a.sor.in, the har#ful =V radiation or different dyes can .e easily co/alently lin1ed to chitosan a#ino,roups. !o#positions .ased on chitosan and other hydrocolloids containin, anti-o6idants, anti-aller,ic, and anti-infla##atory su.stances of /e,eta.le ori,in, ne0 types of depilatory and #eans for curlin, and doin, the hair are .ein, 0or1ed out .y the 0or1ers of Sonat !o., =S-. !hitin, chitosan and their deri/ati/es offer uses in three areas of cos#etics" hair care, s1in care, and oral care. !hitosan and hair are co#ple#entary to each other o0in, to carry opposite electrical char,es" chitosan positi/e and hair ne,ati/e. - clear solution that contains chitosan for#s a clear, elastic fil# on hair, there.y increasin, its softness, s#oothness, and #echanical stren,th. (he #aterial can also for# a ,el 0hen added to #i6tures of alcohol and 0ater. !hitosan can .e used in sha#poos, rinses, per#anent 0a/e a,ents, hair colorants, stylin, lotions, hair sprays, and hair tonics. Se/eral deri/ati/es of chitosan and chitin ha/e potential applications in hair care. (hey include ,lyceryl chitosan, an adduct of an oli,o#er of hydroly:ed chitosan, n-hydro6ypropyl chitosan, 3uaternary hydro6ypropyl-su.stituted chitosan, polyo6yal1ylene chitosan, chitosan oli,osaccharides, chitin sulphate, and car.o6y#ethyl chitin. So#e deri/ati/es of chitosan can for# foa# and create e#ulsifyin, action and chitin po0der can .e used directly in sha#poo. !hitosan and its deri/ati/es ha/e t0o ad/anta,es that #a1e it ,ood candidate for s1in care" one .ein, their positi/e electrical char,e, and the another that the #olecular 0ei,hts of #ost chitosan

&=((- et al." !8I(I+ & !8I(9S-+

2D

products are so hi,h that they cannot penetrate the s1in. (hus, e.,, chitosan can function as a #oisturi:er for s1in. 2ecause of its lo0er costs, it #i,ht co#pete 0ith hyaluronic acid in this application. 2oth chitosan and chitin are already found in crea#s, pac1 #aterial, lotions, nail ena#el, nail lac3uers, foundation, eye shado0, lipstic1, cleansin, #aterials, and .ath a,ents. !hitosan acylated 0ith an or,anic diacid anhydride, and fine particles of chitin or chitosan are used for s1in care. 2oth, chitin and chitosan, can .e used in toothpaste, #outh0ashes and che0in, ,u#. (hey freshen the .reath and pre/ent the for#ation of pla3ue and tooth decay. Salts of chitosan, added to toothpaste, #as1 the unpleasant taste of silicon o6ide and .ind po0ders so that they #aintain their ,ranular shapes. !hitin can also .e applied as a dental filler #aterial and .oth chitin and chitosan a.sor. candida li1e thicans, a fun,us that stic1s to teeth, #a1in, the# candidates to clean false teeth. (he other applications of chitosan are descri.ed else0here and fe0 of these are su##ari:ed"
/ater 0ngineering

and other chitinous #e#.ranes could .e 0idely used for such processes as os#osis, re/erse os#osis, #icro-filtration, desalination, dialysis, and hae#odialysis. 2eds of fla1ed chitosan can also .e DD used for purification of pota.le 0ater .
Paper Industry

2iode,rada.le chitin and chitosan can stren,then recycled paper and increase the en/iron#ental friendliness of pac1a,in, and other products. !hitosan is already in/ol/ed in the #anufacture of paper .ecause chitosan #olecules ,reatly rese#.le those of cellulose the #ain constituent of plant 0alls. It also sa/es che#ical additi/es and increases output. Bastly the paper produced 0ith chitosan has a s#oother surface and is #ore resistant to #oisture. -#on, other thin,s, chitosan is of ,reat /alue in the production of toilet paper and for 0rappin, paper and card.oard. 8ydro6y#ethyl chitin and other 0ater solu.le deri/ati/es are useful end deri/ati/es in paper #a1in, . It can .e used as a .iode,rada.le pac1a,in, #aterial for food 0rap and other products.
-e+tile Industry
.1*)

&ue to its polycationic nature, chitosan can .e used as flocculatin, a,ent. It can also act as chelatin, D2 a,ent, and hea/y #eatls trapper. Feltros01i et al. used chitosan N-.en:yl sulphonate deri/ati/es as sor.ents for re#o/al of #etal ions in acidic #ediu#. D3 In EEE, 2ha/ani and &utta repoted the re#o/al of colour fro# dyehouse effluents usin, chitosan as an adsor.ent. !onsidera.le a#ounts of 0orld production of chitin and chitosan and deri/ati/es are used in D4 0aste0ater treat#ent . !hitosan #olecules a,,lo#erate lar,ely anionic 0astes in solution to for# precipitates and floe, hence it act as a flocculent for recyclin, of food processin, 0aste. !hitosan can co#pete effecti/ely 0ith synthetic resins in the capture of hea/y #etals fro# processin, 0ater. !hitin has .een used to deconta#inate plutoniu# containin, 0aste0ater, and 0ater containin, #ethyl-#ercury 4< acetate , a si,nificant pollutant of 0aste0ater fro# acetaldehyde production. -pplication of chitosan> chitin #i6ture 0as found to re#o/e arsenic fro# conta#inated drin1in, 0ater. !hitosan has also .een found effecti/e in the re#o/al of petroleu# and petroleu# products fro# 0aste0ater. (he deacidifyin, a.ility of chitin is utili:ed in coffee industry and to clarify the .e/era,es such as 0ine, .eer, and fruit ;uices. Re,enerated chitin, chitosan,

&eri/ati/es of chitin ha/e .een produced and used to i#part antistatic and soil repellent characteristics to the te6tiles. In te6tile industry, chitin can .e used in printin, and finishin, preparations, 0hile the chitosan is a.le to re#o/e dyes fro# dye processin, effluents. 2esides these, chitin and chitosan .oth ha/e #ade re#ar1a.le contri.ution to 44 #edical related te6tile sutures, threads, and fi.res .
2ood Processing
**

=se of chitosan in food industry is 0ell 1no0n .ecause it is not to6ic for 0ar#-.looded ani#als. *icrocrystalline chitin 4*!!5 sho0s ,ood e#ulsifyin, properties, superior thic1enin,, and ,ellin, a,ent for sta.ili:in, foods. It is also used as a dietary fi.re in .a1ed foods. (he use of *!! sol/ed so#e of the pro.le#s such as, fla/our, colour, and shelf-life, posed .y other sources of fi.re. It could .e of special i#portance for #anufacturin, proteinfortified .read, e/en 0ithout such in,redients as e#ulsifiers and shortenin,s. !hitin and chitosan act as solid support for the entrap#ent of 0hole #icro.ial, ani#al, or plant cell i##o.ili:ation. !hitin has .een used in i##o.ili:ation of en:y#es. It can .e used as a non-a.sor.a.le carrier for hi,hly concentrated food in,redients, e.,., 47ood dyes and nutrients5. In India, incorporation of chitin in poultry feed at a le/el of 0.D

26

J S!I I+& RGS V9B 63 J-+=-RH 2004

per cent decrease the food consu#ption ratio and increases .ody 0ei,ht .y 2 per cent in co#parison 0ith .irds fed a chitin free diet. Si#ilarly, nutritional studies in the =S ha/e sho0n that chic1s fed on a diet containin, dried 0hey and chitin, utili:ed 0hey #ore efficiently and ,ained #ore 0ei,ht than those fed si#ilar .ut chitin free diet. (rials also sho0ed that s#all a#ounts of chitin added to the diets of chic1s and cal/es ena.led the ani#als to di,est #il1 lactose throu,h increased ,ro0th of specific intestinal .acteria. (hese .acteria i#pede the ,ro0th of other types of or,anis#s and ,enerate the en:y#e re3uired for lactose di,estion. (his property #ay .e of i##ense i#portance, since certain ,roups of hu#an and #any ani#als ha/e lactose intolerance. (here is no co#plete study on the #eta.olis# of chitin and chitosan in the hu#an .ody, therefore, the use of these poly#ers in food processin, industries still needs to .e further e6plored.
!griculture
**

is considered to occur throu,h #any #icro/oids in poly#er. S#all dielectric constants fro# pie:oelectric studies attri.uted the presence of #any #icro/oids in this poly#er structure. (he choice of a #ore suita.le electrode #aterial #ay produce a .etter .attery D< syste# .
Chitosan 5el for %0D and ,%6 !pplications

Recently, dyes containin, chitosan ,els ha/e .een used as potential co#ponents in lasers and other DE li,ht-e#ittin, de/ices 4BG&s5 . (he process, called dopin,, utili:es dyes such as, porphyrin co#pounds that rese#.le the he#e ,roups in .lood. Research on porphyrins and other dyes, such as, fluorinated cou#arin and rhoda#ine 2 for transparent thin fil#s, nic1el porphyrins to in/esti,ate any ne0 properties of fil#s are on the line. 9ne of the authors 4$%&5 at the la.oratory the chitosan containin, a:o#ethine chro#ophore as a pendant ,roup for +B9 applications has .een reported 4=npu.lished results5. Biomedical !pplications of Chitosan (he desi,n of artificial 1idney syste#s has #ade possi.le repetiti/e he#odialysis and the sustainin, life of chronic 1idney failure patients. !hitosan #e#.ranes ha/e .een proposed as an artificial 1idney #e#.rane .ecause of their suita.le per#ea.ility and ,60 hi,h tensile stren,th . (he #ost i#portant part of artificial 1idney is the se#iper#ea.le #e#.rane and so far #ade fro# co##ercial re,enerated cellulose and cuprophane. Since the pri#ary action of the cellulose #e#.rane is that of a sie/e, there is little selecti/ity in the separation of t0o closely related 20 #olecules . (hese no/el #e#.ranes need to .e de/eloped for .etter control of transport, ease of for#a.ility and inherent .lood co#pati.ility. - series of #e#.ranes prepared fro# chitin and 6 its deri/ati/es i#pro/ed dialysis properties . 9ne of the #ost serious pro.le#s of usin, these artificial #e#.ranes is surface induced thro#.osis, 0here hepari:ation of .lood is needed to pre/ent clottin,, and people 0ho are lia.le to internal he#orrha,e can .e dialysed only at ,reat ris1. 8ence, these are the #ost challen,in, pro.le# still to .e resol/ed in the de/elop#ent of #e#.ranes 0hich are inherently .lood co#pati.le. 7ro# these point of /ie0s, chitosan is he#ostatic, i.e., causes clots.
-issue 0ngineering

!hitin treated seeds 40heat5 0ere found to ha/e ,ro0th acceleratin, and ,ro0th enhancin, effects. !hitinous additions to the pottin, #i6tures>soil resulted in si,nificant reduction in root 1not 0or# infestations and suppression of fun,al patho,ens.
Photography
.1.34

In colour photo,raphy, chitosan has .een used as a fi6in, a,ent for the acid dyes in ,elatin and also acts as an aid to i#pro/e diffusion, an i#portant step in de/elopin, photo,raphs.
Chromatographic 'eperations

!hitin and chitosan find 0ide /arieties of D6 applications in chro#ato,raphic separations . (he presence of free -+8 2 ,roups, pri#ary M98 ,roups and secondary M98 ,roups in chitosan #a1es it as an useful chro#ato,raphic support. =se of chitosan in thin layer chro#ato,raphy for separation of nucleic D@ acids ha/e also .een reported. Rhee et al. ha/e used chitin and chitosan as sor.ent #aterial to solid phase e6traction of phenol and chlorophenols .y usin, 8i,h-$erfor#ance Bi3uid !hro#ato,raphy 48$B!5.
'olid 'tate Batteries

&ue to insolu.ility of chitosan in 0ater, it cannot ta1e part alone in fa.rication of solid state protonconductin, poly#er .atteries. (herefore, chitosan is dissol/ed in acetic acid to produce ionic conducti/ity. (he conducti/ity is due to the e6istence of proton in the acetic acid solution. (he transport of these protons

(issue en,ineerin, is the de/elop#ent and #anipulation of la.oratory-,ro0n cells, tissues or

&=((- et al." !8I(I+ & !8I(9S-+

2@

or,ans that 0ould replace or support the function of defecti/e or in;ured parts of the .ody. (he #any potential ad/anta,es of tissue en,ineerin, include the de/elop#ent or re/olution of current technolo,y in total hip, 1nee, cartila,e, tendon, and /ascular replace#ent. *any of these practices at present in/ol/e i#plantation either an autolo,ous or synthetic ,raft in place of the da#a,ed area. Fithin the .ody the i#plant #ust satisfy re3uire#ents relati/e to .ioco#pati.ilty as 0ell as functional and #echanical sta.ility. *any #aterials can react co#pati.ly 0ith the .ody. 2ut unfortunately, they cannot #eet the lon,-ter# #echanical, ,eo#etrical, and functional re3uire#ents of the .ody. (herefore, tissue en,ineerin, technolo,y has .een de/eloped to construct artificial tissues that can #i#ic the natural ones .y co#.inin, 0ith #odulated cells 0ith different types of scaffoldin, #aterials, includin, natural and synthetic poly#ers. -#on, these #aterial polylactide 4$B-5, poly,lycolide 4$J-5 and their copoly#er, polylactide-co-,lycolide 4$BJ-5 ha/e recei/ed #uch attention .ecause of their .iode,rada.ility and .ioco#pati.ility, these are 62 suita.le candidates for tissue en,ineerin, . !hitosan and its so#e dera/ati/es ha/e .een studied for use in se/eral .io#edical applications includin, 0ound dressin,s, dru, deli/ery syste#s, and space fillin, i#plants. 2ut little, in co#parision to these, has .een done to e6plore use of chitosan 0ithin the tissue en,ineerin, paradi,#. chitosan has .een found to ha/e an acceleratory effect on the tissue en,ineerin, processes o0in, to its polycationic nature. (his enhances the cells attraction to this poly#er. It has .een found that de,ree of cell attach#ent also depends on the per cent of deacetylation of the chitosan. In 2000, $rasitsilp et al. sho0ed ho0 de,ree of deacetylation affected in vitro cellular responses to chitosan fro# t0o different sources, shri#p and cuttle fish. (hey e6a#ined four chitosan su.strates, t0o fro# each source, differin, .y a.out 0 per cent in deacetylation and ran,in, .et0een @6 and E0 per cent deacetylation. Results indicated that cells are #ore readily attached to #ore hi,hly deacetylated chitosans fro# .oth sources. In 2003, Fan, et al. ha/e de/eloped a no/el #ethod 4ther#ally induced phase seperation #ethod5 to prepare poly,lycolic acid 4$J-5-chitosan hy.rid #atrices usin, sol/ents of lo0 to6icity 4&*S9 and acetic acid5. (he #atrices 0ith the 0ei,ht ratio of
64 63

$J- to chitosan .ein, @"3 and 3"@ 0ere called the $>!- 4containin, @0 0t per cent $J-5 and $>!-2 4containin, 30 0t per cent $J-5 #atrices, respecti/ely. (hey cultured fi.ro.last cells in &*G* supple#ented 0ith 0 per cent 72S. (hese 0ere seeded onto chitosan and $J--chitosan hy.rid 4 2 #atrices at a density of .D 0 cells>c# . Results indicated that the cell adhesion and proliferation 0as .etter on the $>!- #atri6 than that on the chitosan and $>!-2 #atrices. (he $>!- hy.rid #atri6 0as characteri:ed .y lar,e pore si:e, ,ood #echanical properties and de,rada.ility. (he success of seedin, cells in this #atri6 de#onstrated the potential of the #atri6 as ne0 .io#aterial for tissue en,ineerin,. In a study to #odify $B- surface due to its 6D special acti/ity chitosan 0as used .y Nhu et al . (hey sho0ed that chitosan>heparin 4!S>8p5 co#ple6 0as easily i##o.ili:ed onto the $B- surface, and the .ioacti/ity could .e ,i/en to $B- surface. (his surface of $B->!S>8p should .e in fa/our of li/in, cells. (hey cultured BE2E fi.ro.last cells in a o incu.ator fitted 0ith 0ater-;ac1et at 3@ !. (he incu.ator 0as e3uili.rated 0ith D per cent !9 2 and 0as 1ept at appro6i#ately EE per cent relati/e hu#idity. (hese cells 0ere routinely ,ro0n in &*G* #ediu# containin, 0 per cent 72S and per 2 cent anti.iotic-anti#ycotic in a @D c# cell culture flas1. 7inally, they found that nu#.er of BE2E fi.ro.lasts attached on $B->!S>8p co#ple6 0as #a6i#u# and $B- surface #odified 0ith chitosan had #ore adhesion cells co#pared 0ith that of un#odified $B-. Recently, #any efforts ha/e .een #ade on chitosan for usin, it as scaffoldin, #aterial in tissue 66 en,ineerin,. In 200 , Jarry et al. de#onstrated that chitosan can .e easily processed into porous 6@ scaffolds, fil#s and .eads. %ast et al. sho0ed that chitosan-thio,lycolic acid 4chitosan-(J-5 con;u,ate is a pro#isin, candidate as scaffoldin, #aterial in tissue en,ineerin,. -tte#pts ha/e .een #ade .y *adihally and 6< *atthe0 to de/elop procedures for synthesi:in, #any porous chitosan scaffolds for the applications to0ard se/eral types of en,ineered tissues. In these procedures, first of all, chitosan solutions 0ith concentrations of , 2 or 3 0t per cent 0ere prepared .y direct dissolution in 0.2 M acetic acid. 2ul1 chitosan scaffolds 0ere prepared .y free:in, and lyophili:in, chitosan solutions in pre-cooled, flat .otto#ed ,lass tu.es. $lanar scffolds 0ere prepared

2<

J S!I I+& RGS V9B 63 J-+=-RH 2004

.y free:in, 2D-D0 #B chitosan solution in 0 c# dia# polystyrene petri dishes. (hereafter, they 0ere lyophili:ed. (u.ular scaffolds 0ere for#ed .y free:in, a chitosan solution in the annular space .et0een concentric silicone or $(7G tu.es. !hitosan solution of or 2 0t per cent concentration 0as ad#inistered into the annular space and the 0hole asse#.ly 0as fro:en .y direct contact 0ith dry ice o 4@< !5. (he outer tu.e 0as then re#o/ed and the asse#.ly 0as lyophili:ed. *icroporous chitosan>calciu# phosphate co#posite scaffolds ha/e .een synthesi:ed and characteri:ed for tissue en,ineerin, .y Nhan, and 6E Nhan, . (hey sho0ed that the role of chitosan 0as to pro/ide a scaffold for#, on the other hand, calciu# phophatesL .ioacti/ity presu#a.ly encoura,es osteo.last attach#ent and stren,thens the scaffold. (he co#posite scaffold 0as found to .e stron,er, .ioacti/e and .iode,rada.le. (he effect of this to0ards osteo.last cell attach#ent depends on the ration of chitosan to the t0o types calciu# phosphates 4 -tricalciu# phosphate and calciu# phosphate in/erted ,lass5. (he special attention on chitosan has .een paid for the repair of articular cartila,e. -rticular cartila,e is particularly /ulnera.le to in;ury tra#a, disease or con,enital a.nor#alities .ecause of its a/ascular, alyp#hatic and aneural nature. 9nce da#a,ed, it has little capacity for intrinsic repair. -lthou,h #any repair techni3ues ha/e .een atte#pted o/er the past four decades, .ut none has succeeded to re,enerate lon,-lastin, hyaline cartila,e tissue to replace defected or da#a,ed cartila,e. Recently, preli#inary @0 studies on chitosan-J-J co#posite and its .iolo,ically interaction 0ith articular chondrocytes sho0ed pro#isin, results. !hitosan and its deri/ati/es are .ein, e6tensi/ely used for .one tissue en,ineerin, and central ner/ous syste# also.
/ound "ealing&/ound Dressing
3.132

,reater a#ount of acti/ity than an uncoated control ,roup.

Burn -reatment
32

!hitosan is a pro#isin, candidate for .urn treat#ent. (his is true since chitosan can for# tou,h, 0ater-a.sor.ent, .ioco#pati.le fil#s. (hese fil#s can .e for#ed directly on the .urn .y application of an a3ueous solution of chitosan acetate. -nother ad/anta,e of this type of chitosan treat#ent is that it allo0s e6cellent o6y,en per#ea.ility. (his is i#portant to pre/ent o6y,en-depri/ation of in;ured tissues. -dditionally, chitosan fil#s ha/e the a.ility to a.sor. 0ater and are naturally de,raded .y .ody en:y#es. (his fact #eans that the chitosan needs not .e re#o/ed. In #ost in;uries 4and specially .urns5, re#o/in, the 0ound dressin, can cause da#a,e to the in;ury site.
!rtificial '7in

(he effect of treat#ent 0ith chitosan and saline solution on healin, and fi.roplasia of 0ounds #ade .y scalpel insersions in s1in and su.cutaneous tissue in the a.do#inal surface of do,s ha/e .een reported . (he desi,n for artificial s1in, applica.le to lon,-ter# chronic use focuses on a nonanti,enic #e#.rane 0hich perfor#s as a .iode,rada.le te#plate for the 63 synthesis of neoder#al tissue . It appears that chitosan polysaccharides ha/in, structural characteristics si#ilar to ,lycosa#ino ,lycans can .e considered for de/elopin, such su.stratu# for s1in @3-@D replace#ent . +o0adays the in/esti,ation on .rain-scal da#a,e, plastic s1in sur,ery are .ein, #ade .y the use of chitosan.
6pthalmology

!hitosan has .een found to ha/e an acceleratory effect on 0ound healin,>0ound dressin, process. Re,enerated chitin fi.res, non-0o/en #ats, spon,es and fil#s e6hi.it an increase in 0ound healin, .y o/er 30 per cent. !hitin can also .e used as a coatin, on nor#al .io#edical #aterials. Standard sil1 and cat,ut sutures coated 0ith re,enerated chitin or chitosan sho0 0ound healin, acti/ities only sli,htly lo0er than the all-chitin fi.res. Sur,ical ,au:e coated 0ith re,enerated chitin de#onstrates a su.stantially

!hitosan has replaced the synthetic poly#ers in opthal#olo,ical applications. !hitosan possesses all the characteristics re3uired for an ideal contact lensI optical clarity, #echanical sta.ility, sufficient optical correction, ,as per#ea.ility, partially to0ards o6y,en, 0etta.ility, and i##unolo,ically co#pati.ility. !ontact lenses are #ade fro# partially depoly#eri:ed and purified s3uid pen chitosan .y spin castin, technolo,y, and these contact lenses are clear, tou,h, and possess other re3uired physical properties such as, #odulus, tensile stren,th, tear stren,th, elon,ation, 0ater content, and o6y,en per#ea.ility. -nti#icro.ial and 0ound healin, properties of chitosan alon, 0ith e6cellent fil# for#in, capa.ility #a1e chitosan suita.le for @6 de/elop#ent of ocular .anda,e lens .

&=((- et al." !8I(I+ & !8I(9S-+

2E

Drug Delivery 'ystems

(he applica.ility of natural polysaccharides such as, a,ar, 1on;ac, and pectin in the desi,n of dosa,e @@,@< for#s for sustained release has .een reported . &espite the #edical applications of chitin>chitosan descri.ed a.o/e, they are still utili:ed in the @E phar#aceutical field . It is already 1no0n that co#pounds ha/in, a #olecular 0ei,ht lo0er than 2E00 pass throu,h #e#.ranes deri/ed fro# 20 chitosan . Since chitin and chitosan do not cause any .iolo,ical ha:ard and are ine6pensi/e, these poly#ers #i,ht .e suita.le for use in the preparation of dosa,e <0-<2 for#s of co##ercial dru,s . !ontrolled release technolo,y e#er,ed durin, the E<0s as a co##ercially sound #ethodolo,y. (he achie/e#ent of predicta.le and reproduci.le release of an a,ent into a specific en/iron#ent o/er an e6tended period of ti#e has #any si,nificant #erits. (he #ost si,nificant #erit 0ould .e to create a desired en/iron#ent 0ith opti#al response, #ini#u# side effect and prolon,ed efficacy. (his is a relati/ely ne0 technolo,y and re3uires an interdisciplinary scientific approach. !hitin>chitosan controlled deli/ery syste#s are at de/elopin, sta,e and .ein, used for a 0ide /ariety of rea,ents in se/eral <3, <4 en/iron#ents . Conclusions It is chitin and chitosan 0hich can readily .e deri/ati:ed .y utili:in, the reacti/ity of the pri#ary a#ino ,roup and the pri#ary and secondary hydro6yl ,roups to find applications in di/ersified areas. In this re/ie0, an atte#pt has .een #ade to increase the understandin, of the i#portance and characteristics of the chitin and chitosan .y descri.in, /arious aspects, includin, the che#ical properties, .iolo,ical properties, processin,, and applications. In /ie0 of this, this study 0ill attract the attention of entrepreneurs, industrialists, acade#icians, and en/iron#entalists. 8eferences
2 &utta $ %, Ra/i1u#ar * + V & &utta J, !hitin and chitosan for /ersatile applications, JMS Polym Rev, C92 420025 30@. 8udson S * & S#ith !, $olysaccharide" chitin and chitosan" che#istry and technolo,y of their use as structural #aterials, Biopolymers from renewable resources, edited .y & B %aplan, 4Sprin,er-Verla,, +e0 Hor15 EE<, pp. E6- <. *u::arelli R - -, So#e #odified chitosans and their niche applications, Chitin Han boo!, edited .y R - - *u::arelli and * J $eter 4Guropean !hitin Society, Italy5 EE@, pp. 4@D2.

<

4 D 6

<

20

22

Bi K, &unn G (, Jrand#aison G F & Joosen * 7 -, -pplications and properties of chitosan, "pplications of chitin an chitosan, edited .y * 7 - Joosen, 4(echno#ic $u.lishin, !o#pany, Bancaster5 EE@, pp. 3-2E. 8irano S, N#acyl, N-arylidene- and N#al1ylidene chitosans, and their hydro,els, Chitin han boo!, edited .y R - *u::arelli and * J $eter, 4Guropean !hitin Society, Italy5 EE@, pp.@ -@6. Sashi0a 8 & Shi,e#asa H, !he#ical #odification of chitin and chitosan 2" preparation and 0ater solu.le property of Nacylated or N-al1ylated partially deacetylated chitins, Carbohy r Polym, ): 4 EEE5 2@. Nhan, !, $in, K, Nhan, 8 & Shen J, Synthesis and characteri:ation of 0ater-solu.le o#succinyl-chitosanO $ur Polym J, ): 420035 62E. %i# S S, Bee H * & !ho ! S, Synthesis and properties of se#i-interpenetratin, poly#er net0or1s co#posed of chitin and poly4ethylene ,lycol5 #acro#er, Polymer, ); 4 EED5 44E@. Hao % &, Nhao 7, Bi 7 & Hin H J, !hitosan-.ased ,els, $ncyclope ia of Smart Materials, edited .y * Sch0art:, 4John Filey, +e0 Hor15 <ol .1 2002, pp <2- E0. Buyen & V & Ross.ach V, *i6ed esters of chitin, J "ppl Poly Sci1 ** 4 EED5 6@E. %u.ota +, $er#ea.ility properties of chitosan-transition #etal co#ple6 #e#.ranes, J "ppl Poly Sci1 ;9 4 EE@5 < E. =r.anc:y1 J F & Bipp- Sy#ono0ic: 2, (he influence of processin, ter#s of chitosan #e#.ranes #ade of differently deacetylated chitosan on the crystalline structure of #e#.ranes, J "ppl Polym Sci1 *. 4 EE45 2 E . %urita %, (o#ita %, Ishii S, +ishi#ura S & Shi#oda %, chitin as a con/enient startin, #aterial for acetolysis for efficient preparation of N#acetylchitin to oli,osaccharides, J Polym Sci Part "% Polym Chem1 ). 4 EE35 23E3. !ho.ot V, %re#ena1 J & 9pletal B, Ces!a " Solvens!a &armacie1 99 4 EED5 E0. *u::arelli R - -, &el.en 7, Ilari $ & (o#asetti *, Chimica o''i1 .. 4 EE35 3 . Sal#on S & 8udson S *, !rystal #orpholo,y .iosynthesis and physical asse#.ly of cellulose chitin and chitosan, JMS Rev Macromol Chem Phys, C)3 4 EE@5 EE. " vances in chitin science, edited .y * J $eter, - &o#ard and R - - *u::arelli 4=ni/ersitPt $otsda#, $otsda#, Jer#any5 2000, <ol4 I<. 8udson S * & Jen1ins & F, !hitin and chitosan, $ncyclope ia of polymer science an technolo'y, -hird ed 4Filey Interscience, +e0 Hor15 49nline /ersion, 000.interscience.co#5. &utta $ %, %hatua * %, &utta J & $rasad R, =se of !hitosan-&*-c>Bi!l ,el as dru, carriers, (nt J Chem Sci, . 420035 E3. &utta $ %, Vish0anathan $, *i#rot B & Ra/i1u#ar * + V, =se of chitosan-a#ine-o6ide ,el as dru, carriers, J Polym Mater, .9 4 EE@5 D3 . Ra/i1u#ar * + V, &utta $ % & +a1a#ura S, !hitosana#ine o6ide" a ne0 ,ellin, syste#, characteri:ation and in vitro e/aluations, (n ian J Pharma Sci, ;2 420005 DD. %urita %, !he#istry and application of chitin and chitosan, Polym )e'ra Stab, *: 4 EE<5 @.

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e#ulsion-droplet coalescence techni3ue and characteri:ation, Pharm Res, .; 4 EEE5 <30. (o1u#itsu 8, 8iratsu1a J, Sa1urai H, %o.ayashi (, Ichi1a0a 8 & 7u1u#ori H, Jadoliniu# neutron-capture therapy usin, no/el ,adopentetic acid-chitosan co#ple6 nanoparticles" in vivo ,ro0th suppression of e6peri#ental #elano#a solid tu#or, Cancer +ett, .*> 420005 @@. (a1ashi G, +ano-co#posite fro# natural polysaccharide" de/elop#ent of #echano-che#ical poly#er alloy, "(S* *o ay, . 4200 5 E. Refer Fe.site" 000.aist.,o.;p Hao % &, (u 8, !hen, 7, Nhan, J F & Bin J, p8-sensiti/ity of the s0ellin, of a chitosan-pectin polyelectrolyte co#ple6, "n'ew Ma!romol Chem% "ppl Macromol Chem Phy, 29* 4 EE@5 63. Fan, 8, Bi F, Bu H, Fan, N & Nhon, F, Studies on chitosan and poly4acrylic acid5 interpoly#er co#ple6. II.solution .eha/iors of the #i6ture of 0ater-solu.le chitosan and poly4acrylic acid5, J "ppl Polym Sci, ;. 4 EE65 222 . Be H, -nand S ! & 8orroc1s - R, Recent de/elop#ents in fi.res and #aterials for 0ound #ana,e#ent, (n ian J &ibre *e,t Res, 22 4 EE@5 33@.

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