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Hệ Nano Dẫn Truyền Thuốc Cho Não
Hệ Nano Dẫn Truyền Thuốc Cho Não
Hệ Nano Dẫn Truyền Thuốc Cho Não
TS L Th Hng Nhan
Mc lc
H NANO DN TRUYN THUC CHO NO .......................................................................... 2
1 Gii thiu ................................................................................................................................. 2
2 Cu to hng ro mu no ........................................................................................................ 3
2.1 Lch s : ............................................................................................................................. 3
2.2 Cu to ............................................................................................................................... 4
3 Kim sot thi gian gii phng thuc ...................................................................................... 5
3.1 Gii phng thuc dng Extended-Release formulation ..................................................... 6
3.2 Gii phng thuc dng Sustained-Release formulation .................................................... 7
3.3 Gii phng thuc dng Pulsatile-Release formulation ...................................................... 7
4 Kim sot v tr gii phng thuc theo c ch ch ng .......................................................... 8
4.1. Con ng dn truyn absorptive-mediated transcytosis ............................................... 10
4.2 Con ng dn truyn transporter-mediated transcytosis ............................................... 18
4.3 Con ng dn truyn receptor-mediated transcytosis ................................................... 23
4.4 H dn tryn thuc nhy cm mi trng ....................................................................... 28
5 Kim sot v tr gii phng thuc theo c ch th ng (hiu ng EPR) .............................. 31
6 V d v thit k mt h dn truyn thuc vo no in hnh ................................................ 34
6.1 Khi nim Dendrimer ...................................................................................................... 34
6.2 t vn . ....................................................................................................................... 35
6.3 Phng thc tng hp v c ch dn truyn ................................................................... 36
6.4 Kt qu thc nghim ........................................................................................................ 38
7 Kt lun .................................................................................................................................. 40
Ti liu tham kho ........................................................................................................................ 42
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Hnh 1: Cu to hng ro mu no
3 Kim sot thi gian gii phng thuc
Thng qua iu khin thi gian, cho php thuc t nng iu tr trong t bo.
Hnh 2 th hin nng thuc trong c th theo thi gian ca cc loi thuc thng
thng. Ban u nng thuc tng nhanh sau do qu trnh o thi qua thn v s
chuyn ha, trao i cht (thc bo,.enzyme..) nng thuc gim nhanh. Do cn
phi ch n vn o thi thuc [6].
Nng hiu qu l nng nh nht thuc t hiu qu iu tr. Trong khi ,
nng gii hn an ton l gi tr nng m khi vt qua n s gy c v tc dng
ph khng mong mun cho c th. Do vic thuc b o thi, ta phi s dng nhiu liu
m bo thuc lun t nng tr liu (hnh 2). Tuy nhin nu s dng khng ng
liu lng, gy ra s tch ly vt qu nng gii hn an ton s gy tc dng ph[6].
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Hnh 2 : Nng gii phng thuc theo thi gian ca liu n (tri) v liu a (phi)
3.1 Gii phng thuc dng Extended-Release formulation
S gii phng ca cc tc nhn iu tr trong cc cng thc ban u to ra mt
lng va t nng iu tr v sau tip tc gii phng thuc. Trong qu trnh
gii phng thuc, nng thuc gii phng khng nht thit l hng s nhng phi ko
di c thi gian duy tr nng hiu qu ( hnh 3) . C hai loi cng thc extendedrelease formulations. Th nht l dng polymeric matrix (hnh 3) c cha cc tc nhn
iu tr, s gii phng thuc c kim sot bng cch khuch tn qua cc khe h gia
cc chui polymer h thng mng matrix (s trng n v mt lin kt ngang quyt
nh n kh nng gii phng thuc). Nhng cng thc c p dng cho hydrogel v
nano particles. Th hai l dng polymeric capsules , s phn hy ca lp ph polymer
quyt nh vic gii phng ca thuc[7].
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dn
truyn
cationic
bovine
serum
albumin
(CBSA)
kt
hp
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Hnh 19: Kho st kh nng dn truyn vo no LIP, CLP, v GLP-4 (theo th t t tri
sang phi) bng pht x hunh quang
4.3 Con ng dn truyn receptor-mediated transcytosis
Ni chung, tnh c hiu v chn lc ca con ng hp th qua trung gian
transcytosis ( absorptive-mediated transcytosis) nh hng mc tiu BBB khng cao
v cc cationic proteins hoc CPPs c th tng tc v lin kt vi bt k thnh phn no
c mng t bo tch in m trong c th. Hn na, c tnh v s chng min dch ca
cation protein hoc CPP lm hn ch ng dng trong dn truyn thuc. Trong khi ,con
ng vn chuyn qua trung gian transcytosis ( transporter-mediated transcytosis) da
trn cht nn c tnh chn lc, ch nhng tc nhn thuc c tnh cht gn ging cc cht
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(p<0.01).Cc kt qu trn cho thy TPM c th l h dn truyn nano tim nng cho no
(hnh 23) [21].
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Hnh 23: Kho st thi gian sng ca chut mang khi u no trong th nghim khi iu
tr bng Taxol v TPM
4.4 H dn tryn thuc nhy cm mi trng
4.4.1 H dn tryn thuc nhy cm vi nhit
Trong nghin cu dn truyn thuc, polymer nhy nhit c l l loi c
nghin cu nhiu nht trong nhng h polymer nhy cm vi mi trng. Polymer nhy
nhit c chia l 2 loi: Polymer thun nhit (positively thermosensitive) v Polymer
nghch nhit (negatively thermosensitive). Cc loi polymer thun nhit tng tnh i nc
khi nhit tng lm trng n cu trc, trong khi cc polymer nghch nhit gim tnh
i nc khi nhit tng khin chng co li [22].
t c tnh cht nghch nhit ny , cc polymer phi c t l ph hp gia
cc chui i nc v k nc trong cu trc ca n, v d nh polymer trong nc nhit
phng to lin kt hydro ( ti cc tm a nc), nhng khi nhit tng ln cc lin
kt hydro ny b ph v , tng tc k nc lc ny chim u th v cu trc polymer co
li. Nu t l nhm k nc trong cu trc polymer tng ln th nhit im chuyn pha
t trng thi co sang trng thi trng n tng ln. Nh vy, bng cch kim sot t l
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Hnh 28:Cu trc cc loi copolymer ph bin (tri) v cch thc tng hp cc loi
pegylated PLA immunonanoparticles (phi)[32]
6 V d v thit k mt h dn truyn thuc vo no in hnh
6.1 Khi nim Dendrimer
Cu trc ha hc ca dendrimer bao gm mt li ( cu trc trung tm ) v nhiu
nhnh to thnh mt cu trc hnh cu ba chiu gm cc lp ng tm. Do , cc cu
trc dendrimeric c c trng bi cc lp gia mi tiu im (hoc im cascade) gi
l bc (hnh 29). Nh vy, dendrimer bc 4 l cu trc hnh cu ng tm c 4 tiu im
gia cc li v b mt. Li ca dendrimer l bc khng bi v n khng c tiu im. Cu
trc dendrimer c hai tnh cht quan trng cho qu trnh dn truyn thuc. Th nht l
bn trong hc ca n c c tnh ha hc cho php bao bc cc loi thuc c tnh cht k
nc. Tnh nng quan trng th hai l cc dendrimer cha nhm chc b mt c trng
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Hnh 33: Kho st kh nng dn truyn vo no ca cc h khc nhau qua pht x hunh
quang
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Hnh 34: Kho st thi gian sng ca chut mang khi u no trong th nghim khi iu
tr bng cc h khc nhau
7 Kt lun
Nhng thp k gn y chng kin nhng tin b vt bc trong vic pht trin
cc h dn truyn thuc n no.Cc h nano cho thy kh nng ng dng tuyt vi
thit k cc h dn truyn nh hng mc tiu vt qua hng ro mu no , m ra mt
phm vi rng pht trin cc loi thuc da trn h nano .Tnh cht ha hc ca cc h
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