tiểu luận polymer y sinh

5/26/2018 Ti u Lu n Polymer y Sinh

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MC LC

TIU Trang

I/ Tng quan vvt liu polymer y sinh 1

II/ Phn loi vt liu polymer y sinh 3

III/ ng dng ca vt liu polymer y sinh 10

NHN XT 22

TI LIU THAM KHO 23


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Vt liu polymer y sinh Page 1

I/ Tng quan vvt liu polymer y sinh:

1/ Khi nim:

Polymer y sinh l vt liu polymer (c ngun gc thin nhin, nhn to, hoc

tng hp) c sdng trong y hc vi mc ch iu tr, thay thc quan haychc nng, hoc tng cng chc nng no trong c thngi v ng vt[1].

Mc d polymer y sinh c ng dng chyu trong lnh vc y hc, nhngn cng c thc sdng rng ri trong cc lnh vc khc nh: cng nghsinhhc, mi trng, nng-lm-ng nghip.

2/ Cc yu cu i vi vt liu polymer y sinh:

Tt ccc vt liu polymer y sinh phi p ng y 4 yu cu c bn sau y[1-3]:

Tnh tng hp sinh hc v khng c hi:Vt liu polymer phi thch ng vi cc m, tboni vt liu tip xc; c

khnng kch thch sha hp vi cc m ny. Khng gy sc phn vvi c thsau khi cy ghp cc vt liu ny trong thi gian di. Sxut hin phn ng vimkhi a vt ghp vo c thl hin tng tnhin khi c vt lvo c th, trong

trng hp vt liu c tnh tng thch sinh hc cao th hin tng vim do phnvsht thc trong vi ngy; trong trng hp vt liu khng c tnh tng thchsinh hc vi m tip xc, hin tng vim ko di do c ththc hin phn ngphn vo thi vt ghp ra ngoi c th.

Vt liu polymer phi th hin tnh khng c hi khi thc hin chc nngtrong sut qu trnh sdng trong c thbo m tnh an ton trong qu trnhsdng.

Tnh c thkhtrng:Tt ccc vt liu cy ghp phi c khtrng trc khi thc hin cy ghp.

Cc phng php khtrng thng thng c sdng l: Tia gama, plasma, tiacc tm; cn, v nhit . Cc vt liu ny phi khng bthay i tnh cht, hnhdng v cu trc khi sdng mt trong nhng phng php khtrng trc khia vo c thbo m tnh nng ca chng.


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Tnh chc nng:Mi mt loi vt liu polymer y hc c dng thay th, cha trphi c

mt chc nng c bit ph hp vi mc ch s dng ca n. i khi cc nh

khoa hc c thkt hp nhiu loi vt liu khc nhau p ng chc nng, nhimvca bphn cn thay th.

Tnh c thchto:Vt liu polymer phi c khnng c chto theo hnh dng v kch thc

yu cu. Nhiu trng hp vt liu polymer p ng c cc yu cu trn nhngkhng thchto nn khng c khnng ng dng trong y sinh.

* Ngoi nhng yu cu c bn trn, cn c mt syu cu cthkhc ty theo

tng trng hp sdng v mc ch sdng cthnh:

- Tnh khng phn hy v bn trong mi trng sinh hc: i vi mt strng hp yu cu p ng chc nng trong thi gian di nh: cc ng dn lu,xng, khp.

- Tnh phn hy sinh hc: i vi cc trng hp vt liu p ng chcnng trong thi gian c hn nh: vt liu khung (scaffold) dng nui cy phttrin mt tbo no ; vt liu truyn dn dc phm trong c th.

3/ Tnh hnh ng dng v nghin cu vt liu polymer y sinh ti Vit nam:

Trong nhng nm gn y, nn khoa hc vy tca Vit Nam c nhngbc tin rt ng k. Nhiu thit bv cng nghkhm cha bnh hin i ngangtm thgii c nhp khu vVit nam. c bit, i ng y bc strong nccng dn c o to nhiu nc tin tin trn thgii v dn khng nh vtrkhoa hc ca mnh trn bn thgii.

Tnhng stin btrn, vic sdng cc sn phm y ttpolymer y sinhti Vit nam rt pht trin. Hu nh mi sn phm tin tin nht vmt khoa hcu c ti Vit nam. Trong nhng nm gn y, rt nhiu sn phm y txut phttpolymer y sinh c sdng[14]:

- Hng ngn ngi c t stent ng mch vnh.

- Hng ngn ngi thay khp hng trong nc v nc ngoi.


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- Hng triu ng ng mch cc loi c s dng mi ngy, trong ckhng t cc loi stent t trong c th.

- Cc ca chn thng, chnh hnh nghim trng cn s dng cc vt t y t t

polymer y sinh din ra hng gitrn khp cnc.- Hng trm ngn ngi mc bnh him ngho cn iu trbng phngphp vnchuyn v truyn dn thuc hin i.

Tuy nhin, mt iu cn lu l a stt ccc sn phm vt t, thit bytktrn u c nhp khu tnc ngoi.

II/ Phn loi vt liu polymer y sinh:

n thi im hin ti, c rt nhiu loi sn phm tpolymer y sinh cnghin cu v ng dng gp phn khng nhvo vic cha bn v phc vcucsng con ngi, v c hthng di dy:

1/ Hvt liu polymer y sinh thay thcho xng, khp, gn:

Hin c rt nhiu hvt liu i tpolymer y sinh c sdng trong victhay thv iu trvi mc ch ny nh c trnh by nhdi y[4-5]:

- Cc loi si: CF (carbone fiber), C (carbone), GF (Graphite fiber); UHMWPE(ultra hight molecular weight Polyethylene); PGA (Polyglicolide); KF (Kevlarfiber),

- Cc loi polymer: UHMWPE (ultra hight molecular weight Polyethylene); PGA(Polyglicolide); PLLA (Poly L- lactide); PCLA (poly-caprolactone co-L-Lactide);PCL (poly caprolactone); PET (polyethylene terephthalate); PTFE (polytetra floroethylene); epoxy, PMMA (polymethyl methacrylate),


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Cc vt liu tpolymer y sinh c cha trv thay thcho hxng, khp,gn

Cc loi vt liu cho hxng, gn, khp:


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Cc loi sn phm sdng:

- Cc loi nh v: c vt nh v, thanh nh v.

- Cc loi thay th: khp hng, xng du gi, a m, xng sng,

- Cc loi bxung: rng, polymer tram rng,

2/ Hvt liu polymer y sinh sdng lm hdn lu[4-6]:

i vi cc sn phm dn lu th c thchia lm hai loi theo thi gian sdng:

Sdng ngn hn:Cc loi ng dn lu ny thng chc sdng trong thi gian rt ngn,

sau bi nh: ng truyn v dn dch, nc, mu, cc loi ng thng, Ccloi ng ny thng khng tip xc hoc tip xc hn chvi c thv a slnm ngoi c th. V vy, cc loi ng ny thng sdng vt liu tPE, PVC lchyu.

Sdng di hn:Cc loi ng dn lu ny thng c sdng trong thi gian cng di cng

tt nh: ng thng mt, cc stent ng mch, Stent bang quang, Cc loi ngny thng tip xc vi cc m trong c thv a sl nm trong c th. V vy,cc loi ng ny thng sdng vt liu c cht lng vbn hoc tnh tngthch sinh hc cao nh PTFE, UHMWPE, PCLA, PLLA.

3/ Hvt liu polymer y sinh sdng lm khung xng (scaffold)[5-7]:

Hin nay, hvt liu scaffold tpolymer y sinh phn hy sinh hc c sdngrt nhiu trong vic nui cy v pht trin tbo gc c chc nng chuyn bit.

Scaffold tpolymer y sinh ny slm ga thcc tbo pht trin trn , khihnh dng ca bphn cn nui cy hnh thnh y th polymer y sinh cngc phn hy ht. Kt qu lspht trin ca cc tbo ny s hnh thnh v


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thay thy cc bphn ca c thbkhim khuyt (c bit l cc bphnny l hnh thnh ttbo sng chkhng phi l mt vt liu cht).

Cc loi polymer y sinh phn hy sinh hc c sdng lm scaffold l: PCLA,

PLLA, PLA, PGA, PCLA,Cc tbo gc v cc bphn c ththay thl: Rng, xng, sn, da, .

4/ Hvt liu polymer y sinh phc vchun on[3-5]:

Mt trong nhng lnh vc cc kquan trng trong ngn y hc l chun on vxt nghim, hin c rt nhiu polymer c tnh nng c bit nh polymer dn in,polymer nhy cm vi cc yu tmi trng nh: nng protein, ng, pH,in, ttrng, .. c kt hp vi cc loi vt liu khc nh CNT, kim loi nanonhVng, Bc, oxite st t, chto cc hthit b, sensor v dng cchunonbnh bng hnh nh, in s, mu sc, vi chnh xc rt cao v tin li.cc hthit bny gip cho vic chun on v cha trc thc hin mt cchnhanh chng v tit kim.

5/ Hvt liu polymer y sinh cho vic vn chuyn v truyn dn thuc[8-13]:

Lnh vc t dc mang thuc:Hin nay, lnh vc tng hp polymer y sinh dng t dc phc vcho vic

chto cc loi vin nang nn, vin nang con nhng trn th gii ang to ra mtngun thu cc ln. Mc d cng nghtng hp cc loi polymer ny c trinkhai i tr trn th gii, nhng ti Vit nam, cc cng ty dc phm ch nhppolymer v ch to sn phm m cha ch trng ti vic tng hp ra loipolymer.

Lnh vc truyn dn thuc iu trtrng ch:Trong nhng nm gn y spht trin ca cc cn bnh him ngho nh HIV-

AIDS, ung th, vim gan, c bit l bnh i tho ng ang trthnh mt minguy him i vi sc khe loi ngi. V chng trthnh mt mi lo ngi vcng ln ca cc t chc y t th gii. Vic kim sot qu trnh phn phi


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thuc/protein iu trnhng cn bnh nghim trng trn l mt trong nhng ththch trong lnh vc Y dc. Hin c nhiu loi dc phm (thuc /protein) chngtc khnng cha bnh tt, tuy nhin cc phng php sdng dc phmtruyn thng nh ung, tim, xtr, ha trthhin sgii hn nht nh trong qu

trnh sdng. Tuy nhin, cc phng php sdng dc phm truyn thng iu trcc loi bnh ny c nhng nhc im ln nh: stp trung t ngt cathuc/protein ti mt im, lc thuc/protein trthnh cht c hi cho c thbi v s tp trung lm cho liu lng thuc/protein ti cao hn bnhthng; V dc phm dc dn truyn theo ng mu, chkhi gp tbo mmbnh (ung th) th mi th hin chc nng cha tr, nhng trong qu trnh vnchuyn dc phm ny cn tc dng ln tt ccc tbo khc m n gp. Do chc mt lng nhdc phm c tc dng hu hiu cho vic iu tr, cn phn

ln dc phm li to ra cc phn ng phkhc trong qu trnh iu tr; Thm vo, ssuy gim hnh thc (profile) ca thuc/protein n di khong liu dngtrong qu trnh iu tri hi mt liu thuc/protein mi. Phng php sdngpolyme y sinh c cu trc nano particle nhy cm vi nhit v pH, hoc nhycm vi nhit hoc pH hin c cc nh nghin cu trn thgii nhn nh l

phng php phn phi thuc mt cch tnhin v c trin vng nht bi v ncho php phn phi cc phn thot ng ca thuc mt cch y v hiu quv n mang nhng u im ni tri sau:

Sdng polyme y sinh c thmang v phn phi dc phm vo c thconngi theo nhng chng trnh c vch sn. Nh vy, nng dc phm trongmu v thi gian tc dng ca thuc c thiu khin mt cch d dng nhmtrch hin tng cc bnht thi (hm lng dc phm trong mu cao nht thigy tc dng ph) v c thko di thi gian iu trcho mt ln sdng thuc.So snh v hiu nng s dng iu tr ca phng php mi ny so vi cc

phng php truyn thng c thhin trn hnh sau:


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Hnh thc kim sot thuc/protein

- ng t khc: Hnh thc nh thuc/protein theo phng php truyn thng,phi sdung lp li nhiu ln.

- ng lin nt : Hnh thc nh thuc lin tc thydrogel y sinh. Chsdngmt ln.

Cu trc mng li polyme hydrogel c sp xp vi cc tnh cht ho lddng tng tc vi dc phm. Hpolyme y sinh, c bit l hydrogel y sinhang c ch trng trong vic ng dng vo phng thc cha bnh mi, bi vchng c nhiu u im nh khnng tng thch sinh hc tt, tnh tng tc vidc phm c thkim sot . Mt u im quan trng ca phng thc phn phithuc thydrogel l chng c thkim sot c bi mt vi yu t, v dnh :Kch thc ltrng ca hydrogel, tnh knc, sc mt ca mt snhm chcc bit, chng to ra mt tng tc c trng gia cht mang (matrix) vi thuc

v skim sot phn huca cc hydrogel y sinh.


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C chhnh thnh hydrogel tpolyme y sinh c cu trc nano

particle nhy cm vi nhit v pH khi tim vo c thsng

Mc d tng a ra c nhng bc t ph trong khoa hc, v cc nhkhoa hc trn th gii ang tp trung nghin cu theo hng i ny, tuy nhincngchl nhng bc u nghin cu v cha c mt ng dng c thno do

nhng nguyn nhn sau: Vn tng hp ra loi polymer phi c cu trc thchhp vi nhng iu kin thay i vpH v nhit trong c thcn gp kh khn;Loi polymer phi c kh nng khng c hi, tnh tng ng sinh hc cao(khng bphi ng o thi khi a vo c thngi) v c khnng phn hysinh hc. V nhng l do trn, hin thgii vn ang nlc nghin cu v ngi tadon khnng p dng cc nghin cu ny sbt u c thtrin khai trongtng lai 5 nm sau.


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III/ ng dng ca vt liu polymer y sinh:

1/ ng dng vt liu nano chitosan trong truyn dn thuc:

Tng quan vchitosan:Chitosan l mt loi polymer carbohydrate t nhin c th to ra bng cch

deacetyl ho chitin. Chitosan c thtm thy trong tnhin tng vt gip xcnh tm, cua. Chitosan cn c th c tm thy t nhng loi vi sinh vt nhnm, men.

Chitosan l dn xut deacetyl ho ca chitin, trong nhm (NH2) thay thnhm (-NHCOCH3) v tr C2. Chitosan c cu to t cc mc xchD-glucosamine lin kt vi nhau bi lin kt -(1-4)-glycoside[15][16].

Cng thc cu to ca chitosan

Chitosan c nhng tnh cht sau:

- Khng c, tnh tng ng sinh hc cao v c khnng phn husinh hcnn khng gy dng v khng gy phn ng ph, khng gy tc hi nmi trng.

- Cu trc n nh.- Tan tt trong dung dch acid long (pH < 6,3) v kt ta nhng gi trpH

cao hn, ha tm trong dung dch iod.- C tnh khng khun tt.


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- L hp cht cao phn tnn trng lng phn tca n gim dn theo thigian do phn ng tct mch. Nhng khi trng lng phn tgim th hottnh khng khun v khng nm khng bgim i.

- C khnng hp phcao i vi cc kim loi nng.- pH < 6,3, chitosan c tnh in dng cao.- Trong phn tchitosan c cha nhmOH, -NHCOCH3 trong cc mt xch

N-acetyl-D-glucosamine c ngha chng va l alcol va l amine, va lamide. Phn ng ho hc c thxy ra vtr nhm chc to ra dn xut thO-, dn xut thN-.

- Mt khc chitosan l nhng polymer m cc monomer c ni vi nhaubi cc lin kt -(1-4)-glycoside; cc lin kt ny rt dbct t bi cccht nh: acid, baz, tc nhn oxy ho v cc enzyme thuphn[15][16].

Tng quan vnano chitosan:Chitosan c s dng lm nguyn liu iu ch ht nano chitosan trong

nhng nm gn y v nhng tnh cht u vit ca n kch thc nano. Chitosanl dng deacetyl ha t chitin, c cu trc polysaccharide, c tm thy loing vt gip xc, cn trng v mt vi loi nm. Vi nhiu tnh nng nh tnhtng thch sinh hc, phn hy sinh hc, bm dnh mng v khng c hi, n trthnh nguyn liu cho nhiu ng dng dc sinh hc. Do , ht nano chitosan trthnh hthng phn phi thuc c tim nng ln[17].

Nano chitosan do c kch thc siu nh (t10 n 1000nm) nn ddng iqua mng t bo, c th a vo c th qua nhiu ng khc nhau nh dngngoi da, dng qua ng ming, qua mi. Nano chitosan c din tch v intch bmt cc ln nn c ng dng nhiu trong sinh y hc nh mang thuc,vaccine, vect chuyn gen, chng khun, thuc iu trung th. Khi sdngnano chitosan lm cht dn thuc, thuc iu trc bo vbi nhng ht nanochitosan khi sphn husinh hc. Do kch thc rt nh, nhng ht ny c tcdng thm su vo c th, a thuc n ng mc tiu, nng cao hiu quiutr[18].

Cc phng php chto nano chitosan:Hin nay c nhiu phng php to nano chitosan. Phng php c sdng

nhiu nht l to gel ion, u im ca phng php ny l qu trnh chun bn


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gin v khng cn phi sdng dung mi hu c hay sdng lc nn ln, do phng php ny c nghin cu rng ri trong tng hp cht dn thuc v thcphm chc nng[18].

Nhng yu tnh hng n tnh cht ht nano chitosan nh kch thc ht vs tch in bmt l khi lng phn tv deacetyl ho ca chitosan. Hiuquthu gi thuc ca ht nano chitosan phthuc vo gi trpKa v ho tanca thuc. Thuc kt hp vi chitosan qua tng tc tnh in, lin kt hidro,[18]. Sla chn phng php tng hp nano chitosan cn phthuc vo bncht ca nhng phn thot ng cng nh nhng yu cu dn truyn khc nhau.

1.1: Phng php khu mch nh tng:

Hn hp nh tng nc trong du (w/v) c to ra bng cch phn tn dungdch chitosan trong du. Nhng git lng c lm bn bi cht hot ng bmt.Dung dch nh tng sau c khu mch bng tc nhn to ni thch hp nhglutaraldehyde. Hai nhm CHO ca glutaraldehyde s phn ng vi nhm NH2 ca chitosan khu mch to ht nano chitosan[19].


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1.2: Phng php git t/kt ta:

Phng php ny s dng tnh cht ca chitosan l khng tan trong dungdch kim. Bi vy, chitosan sbkt ta, to git ngay khi dung dch chitosan tip

xc vi dung dch kim. Dung dch kim c th l NaOH, NaOH-metanol hocethandiamine. Dung dch chitosan s c mt thit bnn phun vo dung dchkim to ht nano[19].

1.3: Phng php hp nht git nh tng:

Phng php ny ln u c sdng vo nm 1999. Phng php ny sdng nguyn tc ca chai phng php: to ni ngang nh tng v kt ta. Thayv sdng tc nhn to ni ngang, kt ta to ra bng cch cho cc git chitosankt hp vi cc git NaOH. Mt hnh tng bn cha dung dch chitosan cngvi thuc to ra trong paraffin lng. ng thi, mt hnh tng bn khc chadung dch chitosan v NaOH cng c to ra theo cch nh trn. Khi c hai hnh tng ny c trn li vi tc khuy cao, cc git tmi hsva chmmt cch ngu nhin, hp li v kt ta thnh nhng ht nh[19].


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1.4: Phng php to gel ion:

C chca phng php ny da trn tng tc tnh in gia chitosan tchin dng vmt polyanion nh tripolyphosphate. K thut ny c u im lgiai on chun bn gin v thc hin trong mi trng nc. u tin chitosanc ha tan vo dung dch acid acetic. Sau chitosan c trn ln vi

polyanion to ht nano chitosan di iu kin khuy tlin tc ti nhit phng. Kch thc v in tch bmt c thkim sot bng cch sdng nhngtlchitosan v polyanion khc nhau[19].


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1.5: Phng php mixen o:

Trong phng php ny, ngi ta ha tan cht hot ng bmt vo dungmi hu c to ra nhng ht mixen o. Dung dch lng cha chitosan v thucc thm tt vi tc khuy khng i trnh lm c dung dch. Pha lngc gisao cho hn hp trthnh pha vi nh trong sut. Sau tc nhn to ningang dc thm vo v khuy qua m. C quay loi dung mi. Phn cn liphn tn li trong nc. Dung dch mui thch hp c thm vo kt ta chthot ng bmt. Hn hp c ly tm. Phn dung dch trn cha ht nanomang thuc c chit ra, cho qua mng thm tch 1 gi. ng c cht lng thu

c cho ta bt thuc[19].


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ng dng trong truyn dn thuc ca ht nano chitosan:Ht nano chitosan c kch thc nhnn n thch hp cho nhiu con ng sdng thuc khc nhau nn c phn loi theo con ng sdng:

- Sdng bn ngoi ng tiu ha:Cc ht nano c thc dng trong tnh mch bi v ng knh ca cc mao

mch mu nhnht l khong 4m. Sphn bsinh hc ca cc ht nano c ththay i ty thuc vo kch c, in tch bmt v tnh knc ca chng. Cc htc bn knh ln hn 100nm sbhp thu nhanh chng bi h li-ni m trong

gan, l lch, phi v ty xng. Ngc li, nhng ht nhhn c xu hng c thigian lun chuyn ko di[18].

Cc loi thuc ha hn nht c nghin cu rng ri dn truyn theocch ny l nhng tc nhn khng ung th. Sau khi tim vo tnh mch, nhiu hthng ht nano bao gm nano chitosan c xu hng tch ly li trong mt skhi u


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(Brasseur, 1980; Kreuter, 1994). Nhng ht nano chitosan mang doxorubicin lmchm stng trng ca khi u v nng cao tlsng st ca nhng con chut bcy khi u. Ngoi ra, nhng ht nano chitosan c kch thc nhhn 100nm cto ra cho thy trnh khi h li-ni m v lun chuyn trong mu c lu

hn[18].

- Sdng qua ng ung: tng ht nano c thbo vthuc khng benzyme phn hy trong bmy

tiu ha dn n spht trin cc ht nano thnh nhng hthng dn truyn nhngphn tln, protein v polynucleotide. Phng php ny c nghin cu rng risau mt bo co rng lng ng trong mu ca nhng con chut mc bnh tiung gim sau khi ung nhng ht nano insulin (Damge,1990). Kch thc ht

nhhn 500nm l mt yu tthen cht cho php vn chuyn qua nim mc ruttheo c chendocytotic. Bn cnh enzyme, mng nhy ngn cn skhuych tnca thuc v ht nano, nhng ro cn hp thbiu m l chng ngi chnh chngli shp ththuc protein qua thnh rut. Do , hot tnh ca thuc c thcci thin bng cch kim sot kch thc ht cng vi ko di thi gian lu githuc trong bmy tiu ha. Trong snhng ht nano polymer, ht nano chitosanl cht dn thuc l tng v chng lm tng mc hp thu thuc[18].

Khnng ci thin mc hp thu ca chitosan c nghin cu rng ri. c

tnh bm dnh ca chitosan l do tng tc gia chitosan tch in dng v nimmc tch in m. iu ny lm ko di thi gian tng tc ca thuc v bmthp th[18].

- Sdng qua ng mt:Cc ht nano c nhn thy l cht mang tim nng dn truyn qua ng

mt. Nhiu th nghim cho thy ht nano c khuynh hng bm cht vo bmtbiu m mt. Kt quko di thi gian lu gi, tc o thi thuc chm hn so

vi nhng phng php iu trmt truyn thng, do ci thin dc tnh cathuc. V vy, nhng ht nano c dng dn thuc khng vim, khng dng cho nhng mc tiu iu trvim mt[18].

Chitosan c sdng nh l cht mang dn thuc iu trchng vim mtbi v tc ng thc y mc hp thu thuc. Chitosan khng chgia tng thi gian


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tng tc vi gic mc qua tng tc tnh in gia in tch dng ca n vnim mc tch in m, n cn c khnng xuyn qua lp nim mc, nng caodc tnh ca thuc. Nhm ca Felt (1999) tm thy dung dch chitosan ko dithi gian lu githuc khng sinh trn gic mc ca th. Nhng tc ng tng t

cng c quan st thy khi sdng nhng ht nano chitosan. Nhng ht ny cgitrn gic mc v kt mc ca tht nht 24 gi. Nhm ca De Campos (2001)pht hin thy sau khi s dng nhng ht nano chitosan trn th, hu ht thucc tm thy trong nhng m ngoi mt, gic mc v kt mc trong khi chmtlng thuc nhc tm thy trong nhng m trong mt, mng mt v cht dchlng[18].

2/ Vt liu sinh hc to khung (Scaffold) trong knghm:

Knghm (Tissue engineering) l mt lnh vc lin quan n ng dngcc nguyn tc v cc phng php knghv khoa hc ssng hng ti hiubit c bn cc mi quan hcu trcchc nng ca cc m ng vt c v bnhthng v bnh l pht trin cc vt thay th sinh hc m khi phc, duy trhoc ci thin chc nng ca m. Mc tiu ca knghm l khc phc nhng

hn chca cc phng php iu trtruyn thng da trn cy ghp c quan vvt liu sinh hc[20].

Cc c tnh l tng ca scaffold:- C cu trc l xp bn trong (ng knh l t nht 60 - 100m): tng

trng m, phn bmch, cung cp dng cht.- c chto tvt liu c khnng phn hy sinh hc hoc khnng hp

thu sinh hc c kim sat m sthay thscaffold.- C ha hc bmt thch hp gip cc tbo bm, bit ha v tng sinh.- C cc c tnh c hc thch hp tng xng vi vng ghp.- Khng kch thch bt kphn ng c hi no.- Dto theo hnh dng v kch thc mong mun. Cc vt liu scaffold:- Cc polymer tng hp:


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Cc nghin cu s dng vt liu gm v c t nhin v tng hp (nhhydroxyapatite v tricalcium phosphate) ch to scaffold trong k ngh mxng do cc vt liu ny ging vi thnh phn v ctnhin ca xng v ccc c tnh dn xng. Tuy nhin, cc gm ny c tnh gin (dgy) v khng

ph hp vi cc c tnh chc ca xng. Xng l mt composite gm khunnn polymer c tng cng vi cc phn t gm. Polymer l collagen vhydroxyapatite. Hn na, scaffold gm khng thch hp cho s tng trng cam xp (nhm ctim) v cc m ny c cc receptor tbo v cc cc yu cuc tnh chc khc. Cc polymer tnhin v tng hp l la chn hp dn vlinh hat vng dng cho stng trng phn ln m[20].

Cc polyester nh polyglycolic acid (PGA), polylactic acid (PLLA), cccopolymer (nhPLGA) v polycaprolactone (PCL) thng c sdng thitkcc scaffold. Sn phm phn hy ca cc polymer ny (glycolic acid v lacticacid) hin din trong cthngi v c thi lai thng qua con ng trao icht tnhin[20].

- Cc polymer tnhin:Cc polymer l protein hoc carbohydrate c ngun gc tnhin c sdng

lm scaffold cho stng trng ca vi lai m. Polymer tnhin phbin nhtc sdng to scaffold knghm l collagen[20].

Cc phng php chto scaffold:2.1: Lc gin on qua khun dung mi (solvent-casting particulate-leaching):

Kthut ny bao gm to ra mt dung dch PLLA trong chloroform v thmcc ht mui c ng knh c bit to ra mt dch huyn ph ng nht. Chodung mi bay hi cn li khun nn polymer vi cc ht mui khp bn trong.Sau , ngm composite trong nc lai mui ra v cn li cu trc lxp.

2.2: Bt kh (Gas foaming):

Mt polymer c khnng phn hy sinh hc nhl PLGA c bo ha viCO2 p sut cao. Sau , lm gim nhanh kh nng ha tan ca kh trongpolymer bng cch a p sut CO2trvp sut kh quyn. iu ny dn n sto nhn v khuch trng bt kh vi kch thc 100500 m trong polymer.


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2.3: Mng li si (Fibre meshes/fibre bonding) :

Cc si t cng nghip dt c s dng ch to scaffold t PGA vPLLA. Tuy nhin, cc scaffold ny khng n nh vcu trc nn thng gy ra

sbin dng nghim trng do cc lc co rt ca tbo c nui trn scaffold.iu ny dn n vic pht trin kthut lin kt si tng cng cc c tnhchc ca scaffold. Quy trnh nhsau: ha tan PLLA trong methylene chloride vkhun qua li PGA. Cho dung mi bay hi v sau lm nng khun vinhit trn im nng chy ca PGA. Khi khun PGA-PLLA ngui, lai PLLAbng cch ha tan trong methylene chloride mt ln na. Kt qu l to ra mtmng li cc si PGA c ni mch.

2.4: Tch pha (Phase separation):

Ha tan mt polymer tng hp c khnng phn hy sinh hc trong phenolhoc naphthalene v bsung thm cc phn tc hat tnh sinh hc nhalkalinephosphatase vo dung dch. Sau hnhit thp hn to ra mt stch phalng - lng v lm ngui to thrn hai pha. Lai dung mi bng sthng hoac mt scaffold xp vi cc phn that ng sinh hc bn trong cu trc.

2.5: Lm khun tan chy (Melt moulding):

Dng bt PLGA v cc vi cu gelatin c ng knh c bit lp y mt

khun Teflon. Sau lm nng khun nhit trn nhit chuyn tip thytinh ca PLGA cng vi dng sc p ln hn hp. Phng php ny lm cho ccht PLGA gn kt li vi nhau. Khi lai bkhun, thnh phn gelatin c lc rabng cch ngm trong nc v sau lm kh scaffold. Scaffold c to ra theocch ny c hnh dng ca khun.

Quy trnh lm tan chy khun c bit i kt hp cc si HA ngn. Sphn bu ca cc si HA trong khp scaffold PLGA chc thc thc hin

bng kthut khun dung mi chun bvt liu si HA, khun nn PLGA vgelatin hoc to lbng mui, sau ng dng quy trnh lm khun tan chy.

2.6: Lm kh lnh:

Ha tan cc polymer tng hp nhPLGA trong acid acetic lnh hoc benzen. Sau lm ng lnh dung dch v lm kh lnh to ra khun nn lxp.


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Tng t, cc scaffold collagen cng c ch to bng cch lm nglnh dung dch collagen v sau lm kh lnh. Sng lnh dung dch s lmhnh thnh cc tinh th m s p v tp trung cc phn t collagen vo cckhang khe. Sau , lai cc tinh th bng cch lm kh lnh. C thkim sat

kch thc ltheo tc ng lnh v pH, tc ng lnh nhanh to ra cc lnhhn. Dng ethanol khnc ca collagen ng lnh v lm kh ti imti hn to scaffold collagen. Sau , cc scaffold ny c khu mch bng tcnhn vt l hay ha hc gim khnng ha tan, tnh khng nguyn v tc phn hy.

Cc phng php khu mch vt l gm chiu tia UV, chiu xtia gammahoc phng php nhit lai hydro.

Cc phng php khu mch ha hc lin quan n vic sdng cc tcnhn hai chc nng nh glutaraldehyde (GTA) v hexamethylene diisocyanatehoc bng phng php hat ha nhm carboxyl vi carbodiimide. Cc polymer tnhin khc nhchitin v alginat cng c dng chto scaffold bng phngphp lm kh lnh.

2.7: c khun dung dch (Solution Casting):

Ha tan PLGA trong chloroform, sau ta bng cch thm methanol vo.

Xng lm kh lnh c khkhang c thkt hp vi PLGA, v sau vtliu composite c p vo khun, lm nng n 45 48oC trong 24 gi toscaffold.


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NHN XT

Qua bi tiu lun ta thy c u thvt trt ca vt liu polymer y sinhv tim tng to ln ca vt liu ny khi ng dng vo y hc.

Ngoi ra, c th d dng nhn thy rng: lnh vc nghin cu vt liupolymer y sinh ti Vit nam vn cn rt mi. l mt thch thc i vi nnkhoa hc nc nh. Mc d vy, tim nng vcti chnh v nhn lc stham giavo lnh vc ny cc kln.


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TI LIU THAM KHO

[1] Craig Halberstadt, Dwaine Emerich (2007) Cellular Transplantation fromLaboratory to Clinic. Elsevier Inc.

[2] Teoh Swee Hin (2004) Biomaterials Engineering and Processing Series Vol.1, Engineering materials for biomedical applications. World Scientific PublishingCo.

[3] Kay C Dee, David A. Puleo, Rena Bizios (2002) An Introduction toTissueBiomaterial Interactions. John Wiley & Sons, Inc.

[4] Pathiraja A.Gunatillake and Raju Adhikari (2003) Biodegradable syntheticpolymers for tissue engineering. European Cells and Materials.

[5] Doris Klee, Hartwig Hcker (2000) Polymers for BiomedicalApplications: Improvement of the Interface Compatibility. Springer-Verlag BerlinHeidelberg.

[6] W. Mark Saltzman (2004) Tissue Engineering: Engineering Principles forthe Design of Replacement Organs and Tissues. Oxford University Press, Inc.

[7] U.Kneser, P. M. Kauf mann, H. C. Fiegel, (1999) J. Biomed. Mater. Res. 47,

494.[8] D. P. Huynh, W. S. Shim, J. H. Kim and D. S. Lee (2006) pH/temperature-sensitive poly(ethylene glycol)-based biodegradable polyester block copolyme

hydrogels, Polyme, 47, 7918-7926.

[9] D. P. Huynh, M. K. Nguyen, B. S. Pi, M.S. Kim, S. Y. Chae, K. C. Lee, B. S.Kim, S. W. Kim and D. S. Lee (2007) A new functionalized injectable hydrogel

for controlled insulin delivery. Addvance Materials, 57,1243.

[10] D. P. Huynh, B. S. Kim and D. S. Lee (2009) Controlled release of insulinby a new functionalized injectable hydrogel, Journal of controll release, 67, 1357.

[11] W. S. Shim, Doo Sung Lee (2003) "Micelle Formation of the pH-sensitiveBiodegradable Copolyme Hydrogels", Advanced Polymeic Materials andTechnology (APMT-2003), P-3-38, August 4-7, Gyeongju, Korea.


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[12] W. S. Shim, M. S. Kim, D. S. Lee (2004) "Temperature and pH sensitiveMicellization and Gelation of Biodegradable Block Copolyme Hydrogels", The 8thWorld Conference on Biodegradable Polymes and Plastics, June 1-4, Seoul, Korea.

[13] M. S. Kim, W. S. Shim, D. S. Lee (2004) "A study of polymeic micelle:micellization-demicellization behavior of new pH-sensitive block copolyme", 6thJapan-Korea Symposium on Material & Interfaces, October 21-24, Beppu, Japan.

[14] Phm Ngc Tun (2013) xut nghin cu ng dng chng trnh vt tthit by t, Hi tho KH, HQG. HCM.

[15] M.N.V.R. Kumar (2000) A review of chitin and chitosan application,Reactive & Functional Polymers,46, pp. 1-27.

[16] M. Rinaudo (2006) Chitin and chitosan: Properties and applications,Progress in Polymer Science, 31, pp. 603-632.

[17] H. Zhang, S. Wu, Y. Tao, L. Zang, Z. Su (2010) Preparation andCharacterization of Water-Soluble Chitosan Nanoparticles as Protein Delivery

System, Journal of Nanometerials, 2010, pp. 1-5.

[18] W. Tiyaboonchai (2003) Chitosan Nanoparticles: A Promising System forDrug Delivery, Naresuan University Journal, 11(3), pp. 51-66.

[19] S.A. Agnihotri, N. Mallikarjuna, T.M. Amineabhavi (2004) Recentadvances on chitosan-based micro and nanoparticles in drug delivery, Journal ofControlled Release, 100, pp. 5-28.

[20] Doris Klee, Hartwig Hcker (2000) Polymers for Biomedical Applications:Improvement of the Interface Compatibility. Springer-Verlag Berlin Heidelberg.

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