Tiiu ban Khoa hoc vdt lieu ISBN 978 604 913 1" '''' ''''3 MOT SO LTNG DUNG TRONG Y SINH VA MOI TRlTONG CUA CHITOSAN Tran Dai Lam'''' *, Pham Gia Dien^*, Nguyin Xuan Phiic''''*, Nguyen Hai Binh'''', Mai Thu Trang'''', N[.]
Tiiu ban Khoa hoc vdt lieu ISBN: 978-604-913-1" ''3 MOT SO LTNG DUNG TRONG Y SINH VA MOI TRlTONG CUA CHITOSAN Tran Dai Lam' *, Pham Gia Dien^*, Nguyin Xuan Phiic'*, Nguyen Hai Binh', Mai Thu Trang', Nguyen Thj Ngoan^ Ha Phuong Thu', Pham H6ng Nam', Phan Thi Bich Hoa', Le Quang Duong', VQ Thi Hoa' - Phdng vat lieu Nano Y sinh, Vien Klioa hpc vat lieu 2- Phdng Cdng nghe cac chat cd boat tinh sinh hpc, Vien hda hpc Email: tdlamfojvast.ac.vn Tom tat: Bdi bdo Irinh bdy Idng quan cdc kit qud nghien ciru vd irng dung cua chitosan y sinh hgc (chi tga gdm y sinh nhdn tgo, chi tgo hi ddn ihudc nano, nhiit tri ung thu) vd xir ly mdi trudng (hdp phu kim logi ndng khdng khudn); chUgsgn/chUin Id mdt polysacarit mgch thdng cd ngudn gdc thien nhiin, ed tinh tuang thich sinh hgc egg Ngno chilosgn citng dugc nghiin ciru -phdt triin thdnh hi ddn ihudc irng dung diiu tri nhu cucurmin chua ung thu, hgt nano tir nhiit Iri Trong linh vuc xir ly mdi trirdng, cdc vdt lieu nano (hgt nano tir, hat nano bgc ) dugc pha tgp vdo chitosan di Idng khd ndng hdp phu kim logi ndng vd khdng khudn, khdng li bdo Cdc kit qud nghiin citu dd chitng Id vdt lieu chitosan cd nhiiu tiim ndng ung dung Irongy sinh hgc vd xu ly mdi trudng Abstract: This paper review's some results and applications of chitosan such as artificial bone preparation, drug delivery system, hyperthermia for cancer and environmental treatment (heavy metals adsorption, aniibacleria) Chitin and chitosan are natural polysaccharide and both have a high biocompalibility Artificial bone M'OS successfully fabricated based on chitosan/hydroxyapatite materials Next, nano chitosan particles were developed lo make drug carrier for curcumin deliveiy (as cancer treatment) Nano magnetic particles/chUosan was also used in hyperthermia experiment For environmental field, nano magnetic particles, and chitosan- based silver particles were expected lo help increase heavy metal absorbability and antibacterial activity respectively Briefiy, it was shown that chitosan materials had numerous promising applicalions in biomedical and environmental field I Gioi thieu: Chitosan/ chitin la mdt polisacarit mach thing, cd ngudn glc ty nhien, tap trung nhieu vd cac loai thuy san giap xac nhu tdm, cua, mai myc Nd cd kha nang hda hgp va ly phan buy sinh hpc ddc tinh thap, hoatjinh sinh hpc cao va da dang nhu : khang khuin, khang nam tang sinh te bao tang cudng mien dich cua co thi vdi cac tac dyng kich thich san sinh bach cau giam cholesterol mau, ban chi sy phat triln cua khdi u, cd tac dung tot tren cac vet thuang \'et bdng [1-4] Viec img dyng chitosan cac linh vyc y sinh nhu cbl tao gdm y sinh [5] hoac he dan tbudc nano [6] hay xir ly mdi trudng [3,7-8] da dugc phat triln manh me Trong bai bao nay, chiing tdi trinh bay tong quan cac kit qua nghien ciai irng dung cua chitosan y sinh (ehl tao he din thuoc, hieu img nhiet tri ) va xir ly mdi trudng (khang kliuan hap phu kim loai nang) da dugc tiln hanh tai Phdng Vat lieu Nano Y-sinh, Vien Khoa hoc Vat lieu 168 Hoi nghi Khoa hoc ky- niim 35 ndm Viin KH&CNVN-Hd Ngi -10/2010 Nghien cuu va ung dung chitosan che tao gom y sinh Trong nhirng nam gan day, cac tien bp ve vat lieu gdm y sinh da dugc irng dung va phat trien rat nhieu van de cham sdc siic khde ngudi Trong cac gdm sinh hpc, gdm y sinh tren co sd Hydroxyapatit (HAp) cd nhieu tiem nang iing dyng tinh tuong thich va boat tinh sinh hpc cao, dac biet la nhu cau sir dyng HAp de tao cac san phim xuang dung phiu thuat chan thuang chinh hinh Vat lieu nano HAp/CS dugc tdng hgp tir dung dich theo phuong phap phan ung hda hgc giira mudi chira ion canxi (Ca^"") vdi mudi chiira glc phdt phat (P04^") cd pha trdn chitosan nham myc dich cai thien cac tinh chit ca ly va tang cudng tinli tuong thich sinh hpc De kiem tra boat tinh sinh hpc, compozit HAp/CS dugc ngam mdi trudng gia dich ngudi (SBF - Simulated Body Fluid) khoang thdi gian 14 va sir dyng binh dilu nhiet de giir nhiet dp cua hdn hgp d 37°C Sau cac khoang thdi gian ngam, mau dugc rira sach bang nude cat la lam khd d 80°C rdi dua di phan tich Tir anh FESEM, ta thiy sau 14 thi cac tinh the HAp da bao phu toan bp be mat compozit HAp/CS (khdng thi hien d day) Vdi ket qua thir nghiem chiing td compozit HAp/CS cd boat tinh sinh hpc tit mdi trudng md phdng dich ngudi SBF Ung dung cua chitosan che tao he dan thuoc Mpt hudng mdi img dyng chitosan dupe hpc lam chit mang thuoc cd kicb tbudc nano de mang cac tbudc tri ung thu it tan nude hoac gan cac gen, ADN LTnh vyc hira hen cd nhieu tiem nang vi ddng thdi lam tang dp tan cua cac thulc khd tan nude, kiem soat dugc lieu phan giai, va giam lugng tbudc dua vao dilu tri Tuy nhien, chitosan la polyme cd phan tir lupng Idn nen phan tir klia cdng kenh mat khac chitosan chi tan mdi trudng acid va khdng tan mdi trudng trung tinh va mdi trudng kilm nen ung dung bi han che Glycol chitosan la dan xuat ciia chitosan cd kha nang tan nude mat khac van giir dugc cac dac tinh tdt cua chitosan la kha nang tuong thich sinh hpc va phan hiiy sinh hpc cao khdng gay dpc vdi ca the ngudi nen glycol chitosan dugc sir dyng dl md rdng tac dung ciia chitosan dac biet linh vyc y dugc hpc Biln tinh ky nude cua glycol chitosan nham tao nen cac hat cd cau tnic nano dang mixell cd ciu true ldi vd cd kha nang mang cac thude it tan phan tan vao mdi trudng nude la mdt ITnh vyc dang dugc nhilu nha khoa hpc nghien cuu Chiing tdi chpn tac nhan gossypol nhim biln tinh ky nude glycol chitosan nham tao nen hat GSG cho he dan thuoc nano Vdi diu ua nude va mpt diu ky nude san pham tao se ty co cym tao cau tnic ldi - vd cd dang hat Sau dd, tiln hanh tai thuoc Curcumin ( cd hoat tinh chdng oxi hda, ung thu) len chit mang GSG HOH2CH2COH2C HO HOH2CH2COH2C NH, Hinh 1: Lien kit hda hgc Glycol-Chitosan169 Tiiu ban Khoa hoc vdt lieu ISBN: 978-604-91 -011-3 Hinh anh FESEM cho biet ve cac dac trung hinh thai hpc ciia san phim tao ra, dya tren cac hinh anh FESEM (hinh 2) thu dupe d tren cd thi nhan thiy san phim tao dang hat phan b l tuong ddi ddng deu kich thude khoang 20 - 50 nm Htnh 2: Anh FESEM ciia hgt GCG cd mang curcumin Hieu irng nhiet trj ung thu sir dung hat nano chitosan bien tinh Nhiet tri la mdt lieu phap tri benh nhan loai da biet den tir rat lau Ngay nay, ngudi ta biet rang ddi vdi te bao ung thu cd che dp nhiet tri lieu: viing 42-47°C chira theo each bdc bd (ablation) va viing 47-60°C chira theo each ddt diet te bao ung thu Luu y rang te bao lanh van chiu dupe nhiet dp den ca 70°C Vat lieu hat tir dugc biet den la cd the lam mdi trudng sinh nhiet (tu ddt ndng) dudi tac dyng cua tir trudng xoay chieu vdi yeu cau irng dyng y sinh la phai ben lau va cd thdng sd tdc dp ddt rieng ban dau (Specific Adsorption Rate), SAR = cdT/dt vdi T la dp gia nhiet, t la thdi gian ddt, phai dat du cao -I -15000 -10000 -5000 1- 5000 10000 Magnetic field (Oe/g) Hinh 3; Dudng tu hda cua vdt lieu CS/Fei04 170 15000 Hoi nghi Khoa hgc ky- niem 35 ndm Viin KH&CNVN - Hd Ngi -10 2010 Tinh chat tir ciia vat lieu cd anh hudng quyet dinh den hieu iing nhiet tri Tinh chit tu' ciia \'at lieu CS/Fe304 da dupe khao sat tren he may tinh chit \'at ly (PP.MS - Ph\sics Properties Measurement System) Dp tir hda bao hda cua vat lieu dat khoang 58 emu'g \'di td trudng ngoai khoang 10 kOe Vdi muc dich sir dyng O - cacboxymethyl chitosan lam chit bpc hat sit tir Fe:,04 dl nghien cim kha nang dot nhiet Mpt so ket qua ban diu ciing da thi hien kha nang iing dyng viec nhiet tri dieu tri ung thu Ket qua dot nhiet ban diu cua mau chit Idng tir chua hat Fe304 bpc bdi O - cacboxymethyl chitosan tien hanh d cudng dp tir trudng 80 Oe va tin sl 236 kHz duac the hien tai hinh - -0,10 0,07 0,05 -•-0,03 0,02 0.01 • 100- mg/ml mg/ml mg/ml mg/ml mg/ml mg/ml 80- ^^ ^^ o 1- • 70 •• 60- / 50- 30 200 400 500 800 1000 1200 1400 1600 t(s) Hinh 4: Kit qua ddt nhiit lit ciia hgt tit CS/Fe304 Tir dd thi ta thay vdi ning dp ban diu cua dung dich CS/Fe304 la lOmg/ml, kit qua tic dp gia nhiet va nhiet dp bao hda cung thay ddi tuyin tinh theo cac sy pha loang khac Vdi nhimg ket qua ddt nhi?t ban diu nhu tren chit Idng tir tren eo sd CS/Fe304 cho thiy kha nang img dung viec ddt nhiet dilu tri ung thu Ung dung chitosan hap phu kim loai dung dich 5.1 Hdp phu kim logi ngng Chiine tdi da tons boo nanocomposit Fe304/CS vdi cac chit vd ca phan tan dine nhit cos 150- Energy {keVl a CS/Fei04 10 Energy (keV) b CS/Fei04 sau hdpphyi Ni (II) Energy (kaV) c CS/FesOj sau hdp phu Pb (11) Hinh 5; Phd EDS cua mdng CS/Fe304 trudc vd sau hdp phu Pb(II) vd Ni(II) Phd EDS cua compozit CS/Fe304 sau hip thu Ni(II) (hinh 4b) va Pb(II) (hinh 4c) thi hien cac pic tuong img vdi cac nguyen t l Ni va Pb Kit qua EDS cung cip dir lieu cho su hip phu hieu qua kim loai cua CS/hat tir vdi cac gia tri pic tai 2,34; 10,5 va 13.5 keV su hip phu cua Pb (II) va cac pic tai 7.46 va 8.30 keV su cd mat cua Ni (II) mang compozit 171 Tiiu ban Khoa hoc vdt lieu ISBN: 978-604-913-01 Cac ket qua chimg minh rang Ni (II) va Pb(II) da dugc hip phy hieu qua \'ao be mat mang nanocompozit chitosan/Fe304 Dieu dd chiing td kha nang img dyng vat lieu chitosan de hap phy kim loai nang, lam sach nude va mdi tmdng, sau dd nhd tinh chit tir cua Fe304 ma su thu hdi cac kim loai nang cd the thyc hien dugc dl dang 5.2 Khdng khudn dung djch Compozh chitosan/nano bac (CS/Ag-NPs) dugc nghien ciiu irng dyng viec kliang khuan dung dich nhd dac tinh khang khuan dac biet ciia hat nano bac Chung tdi da tdng hgp vat lieu CS/Ag-NPs dung dich bang phan img giira 25 ml dung dich AgN03 0,1M cd pha them 100 ml chitosan Cac tinh chat ciia CS/Ag-NPs da dugc khao sat bang phd UV-vis, anh hien vi tmyen qua (TEM) [8] Kha nang khang khuan cua vat lieu tren da dugc khao sat vdi mpt sd vi khuan nhu: vi khuan gram am {E.Coli va P.aeruginosa), vi khuan gram duong {Lfermenlum, S aureus vd B sublilis) va nam (C albians); gia tri IC50 dat dugc tuong irng la 2,46; 1,42; 3,9; 6,08; 5,41 va 5,67 mg/ml vdi cac vi khuan tren [8] Dieu dd da chimg minh kha nang iing dyng ciia vat lieu CS/Ag-NPs viec khang khuan dung dich Ket luan Vat lieu gdm y sinb nhan tao da dugc tdng hop cdng tren ca sd vat lieu chitosan/HAp, cac tinh chat hda hpc va boat tinh sinh hpc da dugc khao sat Nano chitosan ciing dugc nghien cim - phat trien he dan thuoc iing dyng dieu tri nhu cucurmin chira ung thu; ben canh dd, hat nano tir/chitosan da dugc tdng hgp cho img dyng nhiet ddt tir (nhiet tri) Trong ITnh vyc xir ly mdi trudng, cac vat lieu nano (hat nano tir, hat nano bae ) dugc pha tap vao chitosan de tang kha nang hap phy kim loai nang va khang khuan, khang te bao Cac ket qua nghien cuu da chimg td vat lieu chitosan cd nhieu tiem nang img dung y sinh hpc va xir ly mdi trudng Loi cam on Cac tac gia chan cam on sy giup da, hd trg kinh phi cua Bd Khoa hpc va Cdng nghe, Vien Khoa hpc va cdng nghe Viet Nam va ho trg ve trang thiet bi cua Vien Khoa hgc Vat lieu, cho nghien cim TAI LIEU THAM KHAO Majeti N.V Ravi Kumar, Reactive and Funclional Polymers, 46, pi (2000) R Jayakumar, Deepthy Menon, K Manzoor, S.V Nair, H Tamura, Carbohydrate Polymers, (2010), doi:10.1016/j.carbpol.2010.04.074 Feng-Chin Wu, Ru-Ling Tseng, Ruey-Shin Juang, Journal Management, 91, p798 (2010) of Enviromental P.K Dutta, Shipra Tripathi, G.K Mehrotra, Joydeep Dutta, Food Chemistry, 114, 4, p 1173 (2009) Tran VTnh Hoang, Nguyen Ngoc Thinh, Le Dieu Thu, Tran Dai Lam, Tap chi Hda hgc, 45, l,tr.79(2007) Tran Dai Lam, Vu Dinh Hoang, Le Ngoc Lien, Nguyen Ngoc Thinh, Pham Gia Dien, Tgp chi Hda hgc, 44, 1, tr 105 (2006) Hoang Vinh Tran, Lam Dai Tran, Thinh Ngoc Nguyen, Materials Science and Engineering; C, 30, 2, p.304 (2010) Hoang Vinh Tran, Lam Dai Tran, Cham Thi Ba, Hoang Dinh Vu, Thinh Ngoc Nguyen Dien Gia Pham, Phuc Xuan Nguyen, Colloids and Surfaces A: Physicochemical and Engineering Aspects, 360, 1-3, p.32 (2010) 172 ... siic khde ngudi Trong cac gdm sinh hpc, gdm y sinh tren co sd Hydroxyapatit (HAp) cd nhieu tiem nang iing dyng tinh tuong thich va boat tinh sinh hpc cao, dac biet la nhu cau sir dyng HAp de tao... khdng gay dpc vdi ca the ngudi nen glycol chitosan dugc sir dyng dl md rdng tac dung ciia chitosan dac biet linh vyc y dugc hpc Biln tinh ky nude cua glycol chitosan nham tao nen cac hat cd cau... che Glycol chitosan la dan xuat ciia chitosan cd kha nang tan nude mat khac van giir dugc cac dac tinh tdt cua chitosan la kha nang tuong thich sinh hpc va phan hiiy sinh hpc cao khdng gay dpc