免费文献传递   相关文献

Corneal penetration of PAMAM dendrimers-coated puerarin liposomes

树枝状聚合物PAMAM包覆葛根素脂质体角膜渗透性研究



全 文 :·
[\Y][
·
ÇÈÉÊ¥‰
PAMAM
ËÌÍ#Î
ÏЕÑÒÓÔ¢/0
P,
]^_
,
`8a

bc

def

bgh

`i

AB¤k ¬k%¬CD­4

Ƭ AB
264005)

Žz
] 


/0ÇÈÉÊ¥‰
PAMAM
ËÌÍ#Î
(puerarin,PUE)
ÏЕƒÑÒÓÔ½¢

¡¢

æ7
PAMAMG2
Y
PAMAMG3
Ë̃Í#ÎÏЕ

ëÍ#ÎûënY]ËÌÍ#ÎÏЕ>™]

Ccü”•ÑÒÓÔ={

-.œËË
ÌÏЕ$

œ-ƒfg¨)‚
(PAMAM/¸
Ï
=01%,05%,10%,20%),PAMAM
™ÑÒÓÔ¢ƒ¦§

ZqÓԛB

£¤
:PAMAM/¸
Ïfg‚>
10%(PAMAMG2)
Y
05% (PAMAMG3)
ƒËÌÏЕƒ
Papp(%#ÓԆB),Jss(ÝÃÏ
!

貈œ©Í#ÎûënY]ËÌÏЕ
(P<001),
(
PAMAM/¸
Ïfg‚>
10%(PAMAMG2)
Y
05% (PAMAM
G3)
ËÌÏЕƒZÑÒÓÔ¢œ© Y‚wË̃ÏЕ
(P<001)。
£V
:PAMAM
ËÌÍ#ÎÏЕ¯ëˆ§¾šÍ
#Όüý6ƒÑÒÓÔ¢

ù>ýk•Jþføé,‰ƒý6»¼Yˆ‰­U


‘
] PAMAM;
ÇÈÉÊ¥‰

Í#Î

ËÌÏЕ

ÑÒÓÔ¢

’w)(
] 20091002

“”„Q
] 
%<‘&¨ÚÛÜ
(30873447)

•d}–
] 
œœÿ

ÒÄ

â®ý ,‰–ÚñY–ñ,‰k•
ƒ/0
,Tel:(0535)6706021,Email:sunkx@ytueducn
  
Í#Î
(puerarin,PUE)
Þ!&Ž‰ÙÍ
Puerar
ialobata(wild)ohwi
m2Íí
Pthomsoni
ƒ2q_
#àᤔT„ƒ
8βD”•!–4′,7Nب
kۅ
。PUE
ŠJ βæ•â#ù,Tßý=
ê

ø*ý6rÏ!Óî²ÒST

½T¾šýUò
ùU
,PUE
$ýnŒDE^%w‚lý±T„s[
ƒ“

‘‚Eƒ
PUE
$ýn.

ý6ˆ‰
­Uƒ

ôÞÜF‚E$ýn‚ƒ˜Œƒ™Á

 $€â®KªÞ{©Ñ҃&ù1‹

PUE
ÓÔ¢ƒ

6­Ùl,95ý=,‰eU

¾š,‰ƒÑÒÓÔ¢

àœ
PUE
$ýnƒˆ‰­
UÞ(†Ý¼ƒ™Á

®Fú`ø

éÆÓÔZCÚ

Méþ%¢¡¢
Ú

)5

*¥Úä
[12],
ëŸLò+l,†‡
[3],
MÏЕ

Ù,+ä¯ë¾šÑ҃ÓÔ¢

àœˆ
‰­U

ËÌÏЕù>¬–ñƒ,‰k•

¯ë.Úñ-.ŠJÏЕYËÌ0)ƒ½¢

½
¯¾“ÏЕƒW¢YœÝ¢

wMŽÊ–ËÌ
ÏЕÞÜF/0ƒ•±
[4]。
Ê-Õ

Õ
[poly
(amidoamine),PAMAM]
>ÇÈÉÊ¥‰$ƒ€
½°<&

+´µ¹$

œU¤³

ÉJ¯ßÙ.•
¤×ƒ=6/

Þ#ŠJ6!¯†½Xƒ%¢
+TÁƒT90”œ¤×

Fú%²
[56]
 ŠJP
ƒˆ‰Ôߢ

$%Þ¢YX#1K¢½±

-.¥
PAMAM
ƒtÛ
NH2
¯ë¤lÐ×G£
>
NH3+。
¢J/0`ø
[7],PAMAM
TêÊÀ$%
`ƒ2·Ü}

øé,‰Œˆ‰ÒƒÔâù

ù±£Sæ7ë
PAMAM
Ë̃
PUE
ÏÐ
•½Ccë%¦

L¤pŠJ
16
€tÛ
NH2
ƒ
PAMAMG2
Y
32
€tÛ
NH2
ƒ
PAMAMG3
™ÏÐ
•CcËÌ

T„3$WƒËÌÏЕ

Ÿ/0ƒÜ
ƒÞHIYœË
PAMAM
ËÌÏЕ™
PUE
ÑÒ
Ô⢃¦§

>àœ
PUE
ý6ˆ‰­U

µõ
–ñý,‰k•Cc?W

1 
0)
+U¤!Ÿ
Zeta
WÄr/9
(PSSNICOMP
380,
Û%
PSS
LM
);
œ+nԍ`9
(Agilent
1100,
GfgLM
);ValiaChien
û>bf4

$%
&.^PJåG/01
);
õn”Oå
(SOR
VALLBiofugePrimoR);
õÌ$%Åså
(Scientz
ⅡD,5–6&:/01)。
PUE(
SG78-,JKLM

ԙ¤×Ð!
41627,
+U
99%,
*A
080702);
AB6!¸Ï
·03·
u
35
Cu

w
2010
n

o
                             
Vol.35,Issue 1
January,2010
(^
P9þ,ªJK L M

+ U
90%,
* A
081012);
)Kf

%,¯ÁG=ÚJKLM

*
A
20080528);PAMAMG2
Y
PAMAMG3(Sigma
L
M
);
Jf>`+

 Y=Úè>¤³+



ªŸ:J

•­
25~30kg,
{á:²þ
æ,JKLMz{‰$Oà†

¥+,A
SYXK

;
)20030020。
2 
Š‹
21 PUE
ÏЕY
PAMAM
ËÌ
PUE
ÏЕƒæ
7
 
<Ò¤f

õ̋æ7
PUE
ÏЕ

áAB
6!¸Ï

)Kf
、PUE
à!

ë©
30mL
vf$

40℃
r·ûw«•ê~b£<Ò

éƝ!ƒ
PBS(pH70)


vWò=nõÌ
10min,
>T
PUE
ÏЕ

æ7
PAMAM
ËÌÏЕ.

>³
PAMAM
YÏЕƒ¨)‚

Ÿz{L
Stewart
‹
[8]
³¸
Ïx!…`}%ÏЕƒ!

v!ƒ
PAM
AMG2
Y
PAMAMG3
ë©
PBS(pH70),
¤pљ
$é„
PUE
ÏЕ$

á·l«jo?@
4h,
>
T
PAMAM
Ë̃
PUE
ÏЕ

22 
`—˜Ÿ¬°¢œË
 SpherisorbODS
ˆ
(46mm×150mm,5μm);ÏÂÔJf01%ƒA
B4ûën
(35∶65);
ˆ·
30℃;
Ïn
10mL·
min-1;
r/ž
249nm。
>{, ¬°¢

¤pá
©+ën

xJÑÒ=߉ƒ©+ënY
PUE
©+
ënm
20μLCŽ,¤”/,¿¬`f。
23 
ü”•ÑÒÓÔ={
 

ValiaChien
bf
4ÑÒÓÔCo
[9],
ᕭ>
25~30kg
ƒ<ü

Dß&ElFu.ÒGGH

Žnáý0

I
”ýÑÒ½©+ënô{K©¼€µ4Ò
`
,^
_¸JãŽâ4

=_¸Jã}æ4

>g5
ÑÒKJƒ|›

ØËé
50mL
©+ën©}æ
4

xéÆ
45mL
,‰©Žâ4
。37℃
r·ûw
«™¼µ4Ccjo?@

½-.EÆ
CO2Y O2
(95∶5)
ƒò¥l•

¤pŒ
025,05,075,10,
125,15,175,20,25,30h
ý}æ4áŽ
200
μL,-.é200μL。Žâ12000r·min-1”O
10min,
á^Gn
20μLCˆ,HPLC/ PUEe
U

Zq
PUE
åuÔâ!

24 
œ-Bƒ
PAMAM
ËÌ
PUE
ÏЕ™ÑÒ
ƒÓÔ¢¦§
 
¤pá
PAMAMG2(PAMAM/¸
Ï
ƒfg¨)‚>
10%)
Y
PAMAMG3(PAMAM/¸
σfg¨)‚>
05%)
ËÌÏЕ©Žâ4

ë
PUE
ûënY]ËÌÏЕ>™]

î
23
Û0ù

/œ-Bƒ
PAMAM
ËÌ
PUE
ÏЕƒÑÒ
ÓÔ¢

25 
ËÌ
PUE
ÏЕ$
PAMAM
ƒ¨)‚™ÑÒ
ƒÓÔ¢¦§
 
>?0
PAMAM
ËÌ
PUE
ÏЕ
$
PAMAM
YÏЕƒ¨)‚ÓÑÒÓÔ¢ƒ²
†

Œ
PAMAM(G2,G3)
Y¸Ïƒfg¨)‚¤p
>
PAMAM/¸
Ï>
01%,05%,10%,20%
—˜
«

î
23
Û0ù

/ ÑÒÓÔ¢

26 
ÑÒÓԛBƒZq
 
”•ÑÒÓԛB{
ë«Lñ­T

Qn=V0(Cn+V/V0
n-1
i=1
Ci)=V0Cn+V
n-1
i=1

Papp=
△Q
△t·C0·A·60
;Jss=C0·Papp;D=δ
2/6τ;
K=Jss·δ/D·C0。
 $
Qn>PUEåuÔâ!,V0>}æ4ën
•u
,V
>᎕u
,C0>†l4ç ,‰eU,A
>J+u
(0781cm2),Papp>%#ÓԆ
B
,Jss>ÝÃÏ!,D>Ñ҃bf†B,δ>ÑÒ
KU
(00597cm),τ>.#,È|…ƒ;…6¤U
øÓ.`LÔÿ1T
,K
>Ñ҃¤S†B

3 
´—
31 PAMAM
ËÌ
PUE
ÏЕƒæ7
 PAMAM
Ë
Ì
PUE
ÏЕ

+äø6
,Zeta
WÄ{¦“$

ËÌFÏЕ>è+äY
Zeta
WĤp>
3588
nm
Y
-1216mV,PAMAMG2
Y
PAMAMG3
ËÌ


>è+ä¤pøé„
3794nm
Y
3788nm,
>
è
Zeta
WĤp“>
2121mV
Y
2083mV。
ô
‚²
PAMAM
Œ
PUE
ÏЕƒ%¢”£¸
Ž

øéëÏЕ+ä

-..ÏЕˆ$W¢

%
²±T„
PAMAM
ËÌÏЕ

32 
}æn
PUE
r/Š‹
 
¬°¢œËJf
1,¯
J

©+ënYÑÒ=߉œ23
PUE
ƒ/

PUE
Œ©+ën$ƒ(W|…Šã>
A=
88973C+15811(n=7),R2=09999,
…¢^ž
01~160mg·L-1,
œ

$



;eUƒ>踼
›¤p>
10384%,10156%
Y
10114%,
p=
RSD
¤p>
24%,11%
Y
09%;
p`
RSD
¤p
>
17%,24%
Y
11%(n=5)。
33 
œ-Bƒ
PAMAM
ËÌÏЕ™Ñ҃Ó
Ô¢¦§
 
á
PAMAMG2(10%)
Y
PAMAMG3
·13·
u
35
Cu

w
2010
n

o
                             
Vol.35,Issue 1
January,2010
  
APUE
ƒ©+ën
;B
xJÑÒ=߉ƒ©+ën

C
©+ën
;1PUE。
f
1 
©+ënŸ xJ
PUE
YÑÒ=߉ƒ
HPLC
f
(05%)
Ë̃ÏЕ©Žâ4

ë
PUE
ûënY
]ËÌÏЕ>™]

/0ËÌÏЕƒÑÒÓÔ
¢
。PUE
ûënY
PAMAM
ËÌFÏЕƒåu
ÑÒÓÔ|…Jf
2,
{f
2¯
J

ÏЕƒåuÔ
â!A

ôÓFú`ø
[10]
$¢ÏЕˡèÏë
  
¢,‰ôœT²ˆøéÑ҃ÓÔ‹
。PAM
AM
ËÌ

 v€.`±ƒåuÔâ!®œ©
PUE
ûënY
PUE
ÏЕ

½(
PAMAM G3
(05%)
ƒZÑÒÓÔ+—AB

”•ÑÒÓԛ
BJ%
1,¯
×
,PAMAMG2(10%)
Y
PAMAMG3
(05%)
ËÌÏЕƒ
PappYJss貈œ©PUEû
ënY
PUE
ÏЕ
(P<001),
(
PAMAM G3
(05%)
ËÌÏЕƒ
PappY JssÓ PAMAM G2
(10%)
ËÌÏЕ|ŠJjkˆ§¢
(P<001)。
f
2 PAMAM
ËÌFÏЕY
PUE
ûën
ƒ”•ÑÒåuÓÔ|…
(n=6)
%
1 PAMAM
ËÌFÏЕY
PUE
ûënƒ”•ÑÒÓԛB
(n=6)
;p
Papp×106
/cm·s-1
Jss×103
/μg·s-1·cm-2
D×107
/cm2·s-1
K×10
PUE
ûën
146±039 657±171 451±036 194±021
PUE
ÏЕ
065±006 293±026 507±211 076±011
PAMAMG2(10mol%)
ËÌÏЕ 198±0232,3) 888±1022,3) 818±0492) 145±0093)
PAMAMG3(05mol%)
ËÌÏЕ 295±0111,2,3) 133±0991,2,3) 695±1212) 253±0153)
  
A

Ó
PAMAMG2
ËÌÏЕ;Ԃ
1)P<001;
Ó
PUE
ûën;Ԃ
2)P<001;
Ó
PUE
ÏЕ;Ԃ
3)P<001。
34 PAMAM
ËÌÏЕ$
PAMAM
ƒéÆ!™Ñ
҃ÓÔ¢¦§
 
íî
PAMAM
éÆ!ƒøé

PUE
ÑÒÓÔ¢JËøé•?ƒHI

 ÑÒå
uÔâ!Jf
3~4,
”•ÑÒÓԛBJ%
2。
¯
J
,PAMAMG2
ËÌÏЕ
(10%)
Y
PAMAMG3
ËÌÏЕ
(05%)
v€.`±ƒÑÒåuÔâ
!
、Papp,Jss,DYK蜩 Y‚wƒËÌÏЕ。
4 
’
Ÿz{>T„ƒœË¡›ƒÏЕ

L,Ï
‚Y¸ÏÓ)Kfƒ‚äêΜË5Š

Ë¡›
ƒ„
50%
ë^

ÓFú`ø¨Ÿ‹
[11],
[¥ËÌ
  
f
3 PAMAMG2
œ-¨)‚ËÌ
PUE
ÏЕ
ƒ”•ÑÒåuÓÔ|…
(n=6)
·23·
u
35
Cu

w
2010
n

o
                             
Vol.35,Issue 1
January,2010
f4 PAMAMG3
œ-¨)‚ËÌ
PUE
ÏЕ
ƒ”•ÑÒåuÓÔ|…
(n=6)
/0ƒ={®­
。PAMAM
ÓÏЕƒÔ-ùŒ
%±JFú`ø

 â®°&WžoYMûžo
Ó¸ÏÒbˆ»é
[12]。
 $

ù°ç$W3ÓÏ
Е%¢¦W3bˆ»é¯TÞ⮃ùo

ÑÒ^_$%>,‰ÔâÑ҃â®Kn&


ÑÒ^_$%Òò¦W3
。PAMAM
™
PUE
Ï
ЕËÌ
,PUE
ƒÑÒåuÔâ!øé
,¯

ò$W3ƒ
PAMAM
Óò¦W3ƒÑÒ^_$%E
â&Wù

ÊÀëÑÒ^_$%`ƒ

2·Ü}

(tightjunction),
.,‰Eâ$%NVãä
(paracel
lulartransport)
CÆ$%`O

øéëÑ҃ÓÔ
¢

-.
,PAMAMG3
ËÌÏЕƒåuÔâ!ð
  
%
2 PAMAMG2
Y
PAMAMG3
œ-¨)‚ËÌ
PUE
ÏЕƒ”•ÑÒÓԛB
(n=6)
PAMAM
/mol%
PAMAMG2 PAMAMG3
Papp×106/
cm·s-1
Jss×103/
μg·s-1·cm-2
K×107/
cm2·s-1
D×10
Papp×106/
cm·s-1
Jss×103/
μg·s-1·cm-2
D×107/
cm2·s-1
K×10
01 081±011 366±096 391±042 124±019 121±028 539±054 449±097 159±021
05 103±033 462±128 563±051 109±022 295±011 133±099 695±121 253±015
10 198±023 888±102 818±049 145±009 214±016 962±214 595±136 214±022
20 176±019 794±201 743±071 141±026 143±009 644±217 484±092 177±008
©
PAMAMG2
ËÌÏЕ

ô‚²
PAMAM
ÊÀ$
%2·Ü}ƒToÓR
NH2ƒ€BJ²,ÈÓ$
W3*PJ²

ôÓ
KitchensKM
ä
[7]
™œ-B
PAMAM
¯ëœ-ãUƒÔâ
Caco2
ø$%ƒå
椳Þ‹ƒ

,‰ý6Ô⻼ƒãUYn›Vëâ®ÓÑ
Ò&J²

MÓ,‰ƒøG½¢Ÿ•o¡¢


JFú`ø
[13],
,‰EâQñc¸Þæbf
êæ

,‰ÔâÑÒZÞÒê
。PAMAM
³¯ë
ÊÀÑ҃$%`O

@ª>
PAMAM
™
PUE

ëù

Å
PAMAM
éƃ€.

†l4
PUE

‚YÉÃ

,‰ƒ•o¡¢œ

Ñ҃ÓÔ¢í
PAMAM
ƒøéø6


PAMAM
â!

,‰ƒ
•o¡¢ß

={$
PAMAMG2
Y
PAMAMG3
ƒfg¨)‚¤p>
20%
Y
10%
.
,¯
T±â
!
,PUE
•o¡¢ß

ÓÔ¢•?

PAMAMG3
‚
PAMAMG2
ŠJÀîƒR¨
ÁY=6/

øëToÀ*


PAMAMG3
‚
PAMAMG2
À鲈ƒß
PUE
ƒ•o¡¢

’
PAMAMG3
Œfg¨)‚>
05%
.ZÓÔùƒ
„A6


PAMAMG2
Z>
10%。
¢^1÷
,PUE
ÏЕ
PAMAM
ËÌ

ZC
ë,‰ƒÑÒÓÔ¢

àœëˆ‰­U
。PAMAM
ËÌÏЕJþf£>–ñý6,‰k•

 Ó
ÑÒùƒåæJ†Cè/0


—˜™š

[1] NanjawadeBK,ManviFV,ManjappaASInsituforminghy
drogelsforsustainedophthalmicdrugdelivery[J]JControlRe
lease,2007,122(2):119
[2] KaurIP,SmithaRPenetrationenhancersandocularbioadhe
sives:Twonewavenuesforophthalmicdrugdelivery[J]Drug
DevIndPharm,2002,28(4):353
[3] VandervoortJ,LudwigAOculardrugdelivery:Nanomedicine
applications[J]Nanomed,2007,2(1):11
[4] PhetdeeM,PolnokA,ViyochJDevelopmentofchitosancoated
liposomesforsustaineddeliveryoftamarindfruitpulp'sextractto
theskin[J]IntJCosmetSci,2008,30(4):285
[5] SvensonS,TomaliaDADendrimersinbiomedicalapplica
tionsreflectionsonthefield[J]AdvDrugDelivRev,2005,57
(15):2106
[6] PatriAK,KukowskaLataloJF,BakerJRJrTargeteddrugde
liverywithdendrimers:comparisonofthereleasekineticsofcova
lentlyconjugateddrugandnoncovalentdruginclusioncomplex
·33·
u
35
Cu

w
2010
n

o
                             
Vol.35,Issue 1
January,2010
[J]AdvDrugDelivRev,2005,57(15):2203
[7] KitchensKM,KolhatkarRB,SwaanPW,etalGhandehariH
transportofpoly(amidoamine)dendrimersacrossCaco2cel
monolayers:Influenceofsize,chargeandfluorescentlabeling[J]
PharmRes,2006,23(12):2818
[8] RogerCCNewliposomes:Apracticeapproach[M]Oxford:
OxfordUniversityPress,1994:108
[9] MajumdarS,HippalgaonkarK,RepkaMAEfectofchitosan,
benzalkonium chlorideandethylenediaminetetraaceticacidon
permeationofacycloviracrossisolatedrabbitcornea[J]IntJ
Pharm,2008,348(1/2):175
[10] SinghK,MezeiMLiposomalophthalmicdrugdeliverysystem
I:Dihydrostreptomycinsulfate[J]IntJPharmacol,1984,19
(3):263
[11] 
,PC

Rl…

S‚3

ä

ŽÊ–ËÌÍ#ÎÏЕƒæ
7ŸøG¢ÐœË
[J]
$,0
,2007,30(1):89
[12] KlajnertB,EpandRMPAMAMdendrimersandmodelmem
branes:Diferentialscanningcalorimetrystudies[J]IntJ
Pharm,2005,305(1/2):154
[13] LoftssonI,StefanssonEEfeetofcyclodextrinsontopica1drug
deliverytotheeye[J]DrugDevelIndPharm,1997,23(9):
473
CornealpenetrationofPAMAM dendrimerscoatedpuerarinliposomes
LIUYi,SUNKaoxiang,YAOWenjun,LIANGNa,MUHongjie,LIANGRongcai,YAOChen
(SchoolofPharmacy,YantaiUniversity,Yantai264005,China)
[Abstract]  Objective:TostudythecornealpenetrationofPAMAMdendrimerscoatedpuerarinliposomesinrabbitsMeth
od:EvaluatedPAMAM(G2,G3)dendrimerscoatedpuerarinliposomeswerepreparedandtheinvitrotranscornealpenetrationwere
comparedtopuerarindropsolutionanduncoatedliposomesTheefectofdiferentproportionofPAMAMtophospholipidsinformula
tiononcornealpenetrationandthepenetrationparameterswereinvestigatedResult:Thesteadystatefluxesandpermeabilitycoefi
cientsofpuerarinbyPAMAMG2(10%)andPAMAMG3(05%)coatedpuerarinliposomesweregreaterthanthatbypuerarindrop
solutionanduncoatedliposomess(P<001),meanwhilethePAMAMG2(10%)andPAMAMG3(05%)coatedliposomeswerebet
terthanotherratiosofcoatedliposomesforimprovementofcornealpenetration(P<001)Conclusion:ThePAMAMcoatedliposomes
isabletoenhancethecornealpenetrationofpuerarinandpromisingasanoculardrugcariers
[Keywords]  PAMAM;dendrimer;puerarin;coatedliposomes;transcornealpenetration
doi:10.4268/cjcmm20100106

›œ-0
 
§¨

·43·
u
35
Cu

w
2010
n

o
                             
Vol.35,Issue 1
January,2010