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Preparation and in vitro evaluation of tetrandrine-loaded composite microspheres embedded with PLGA nanoparticles

内嵌汉防己甲素纳米粒的复合微球的制备与体外评价研究



全 文 :2016
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] 20151213

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] 
h‹Œü¨g*xy
(2014CFB403)

yzA{
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žŸ

ÆoZj
,Tel:(027)85726073,Email:like19988021@163com

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ÆoZj

qr‡ˆˆçZHíî
,Email:29136909@qqcom
Preparationandinvitroevaluationoftetrandrineloadedcomposite
microspheresembeddedwithPLGAnanoparticles
SHIChen,MENGRui,LIKe
(UnionHospital,TongjiMedicalColege,HuazhongUniversityofScienceandTechnology,Wuhan430022,China)
[Abstract] Inthispaper,wepreparedatypeofcompositemicrospheresembeddedwithpoly(lacticcoglycolicacid)(PLGA)nan
oparticlesforeficientinhalationdeliveryoftetrandrine(Tet),whichisatraditionalChinesemedicineforanticancer,andstudiedits
morphology,drugreleaseprofile,cytotoxicityandcelularuptakebehaviorPLGAnanoparticlesloadingtetrandrinewerepreparedby
emulsionsolventdifusionmethod,andcompositemicrosphereswerepreparedbyspraydryingmethodwithmannitolasmatrixduetoits
osmoticefectScanningelectronicmicroscopy,dynamiclightscateringlaserparticleanalyzerandconfocalmicroscopywereappliedto
characterizethemorphologyandsizeofthemicrospheresThedrugloadingrate,drugencapsulationeficiencyanddrugreleaseproper
tieswereexploredbyRPHPLCThecytotoxicityinA549celsbetweencrudedrugofTetandTetloadedmicrosphereswerecompared
byMTTassayThecelularuptakebehaviorofmicrospheresinA549celswasinvestigatedusingconfocallaserscanningmicroscopy
Theresultantmicrosphereswerecomposedof189nmPLGAnanoparticlesexhibitedsizesrangingfrom1to3μm,withthehighestdep
ositioneficiencyThemicrospherescaneasilybedissolvedinamimiclungenvironmentandreleaseredispersiblePLGAnanoparticles
ComparedwithcrudedrugofTet,Tetloadedmicrospheresshowedacertainsustainedreleasepropertyandhighercytotoxicityefectto
A549celsThecelularuptakeexperimentdemonstratedahigherexcelentpenetrationabilityofcelstonanoparticlesandtimede
pendentuptakeprocessThisstudyprovidesabasisfordevelopingnewinhalationtherapiesforlungcancer
[Keywords] tetrandrine;nanoparticle;microsphere;pulmonarydrugdelivery;lungcancer
doi:10.4268/cjcmm20160513
·838·
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Vol41,No.5 March,2016
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Vol41,No.5 March,2016
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1 
èéêëìŽ[ê}‘—, 
(n=3)
Table1 EntrapmenteficiencyanddrugloadingofTetloaded
compositemicrospheres(n=3) %
èéêëì

òó£Ÿ
/g·g-1 5/50
[ê}
(EE) 8764±532
—, 
(DL) 298±0112
34 
öÖ¥,¡Â
±
Tet
/q,

—
Tet
ðñòóûô|ì,.¥
 ãä

q
7)。Tet
/q,o
8h
8îêÎ
9399%。
Y±¤/q,

—
Tet
Žðñòó|ì¥
 u o
8h
8G¯
5152%,
-oYŽOÊq
8

ðñòóŽÍž±íþ¤/q,

mBCàŽ
á¥ÉÊ

îç/®«
PLGA
o̓Ÿ$áï_
â

,.ð*祠

¥ ž±ª
PLGA
_➱
ç

o̓ŸŽÇ-
8h
8

,¤ê¥W²Ž%
&
,PLGA
íîï<_âë

vQ
Tet
¥ Ñ(
ù

Ú«(6dOʶý
,PLGA
_➱w
ì
,Tet
Ž¥ Ñ&á

n/á怒î2Òó
,.oÎê?“1XýÑý¥ 

±Ñ°,.o2
3¿j8Ž:ì«B:Ž

35 
¿jSÂ
ÉÊ
MTT
¶‡×±!·
PLGA
íîï<
、Tet
/q,

—
Tet
Žðñòóohi
A549
¿j$Ž¿
jS¼n¿Ìù

q
8),24h
8]G±Ž!·
òó±¿jŽSÂ{ò

$þG±{Ž¿jæ°}
í°¤
90%,
á^°G±{
(13g·L-1),
¿jæ
°}Ño
85%


€T!·òó±¿j«5w
Ž

±§
Tet
/q,ª—
Tet
ðñòó±¿jŽ
·248·
¤ 


8çèéêëìíîïŽðñòóŽôõªöÖ÷ø˜™
  
q
7 Tet
/q,˗
Tet
ðñòóŽ|ì,.¥ ãä±
§
(n=3)
Fig7 InvitroreleaseprofileoftherawTetpowderandTet
loadedmicroshperes(n=3)
Wy

q
9),
î2ÝÎ(,.G±ww

¿jSÂ
Ñ&ww

ڗ
Tet
òó±hi
A549
¿jŽSÂ
ÙCà

¡×«$

°| {Ž±§Bà{ÂKÿ

µ’yóC

ðñòó±23¿jŽKô‘LKÉ
Ê&¤/q,

mö/®o¿jŸ-TU1‡œ

q
8 
!·ðñòóŽ
MTT
TU
Fig8 ThehistogramofMTTassayofblankmicrospheres

—èéêëì
PLGA
íîïòó{Ž¿jæ°}à{þ¤èéê
ëì/q,{
(n=6,P<005)。
q
9 Tet
/q,

—
Tet
ðñòóŽ
MTT
TU
Fig9 ThehistogramofMTTassayofrawTetdrugandTet
loadedcompositemicrospheres
36 
¿jŸ-
¯¼[çU€¿jSÂTU’y

#ðñòó
ª
A549
¿j¼n¿Ö¬–

Ìù¿jo]OÊ
q
(2,4,8h)
±ðñòóŽŸ-

q
10)。2h
8

¿
jt1áîx²>íîï<
,´
#‡¢‡T‹?

óC¿j±íîï<ŽŸ-«%Ž

(6dO
ʶý

íîï<ŽŸ‚]Rwù
(4,8h),
!o¿
jt1r8jÚ

B^•kBíîï<‚jH
+ð8Çöǽ

®úoàòL+´ŠGg‹?

¼ù¼‚Í$öðF_



oµÒÓ$íîï
<ø—,.+ð¥ 

muÉÊ

A2h;B4h;C8h;
Ú>1+¯
DAPI
Ž¿j

²>1+¯ð
ñòó

¥ 

Ž—
Tet
Ž
PLGA
íîï<

q
10 A549
¿jŸ-—
Tet
ðñòóŽq+ÖgÎq>
Fig10 CLSM imagesofthecelularuptakeprocessofTet
loadedcompositemicrospheresinA549cels
4 
Àª’À


±hiŽ,.‘ÈdïBWŽÏh^
,_`

ùà‚|¦ïŽw:«%&Ìoh12_
1XŽ¬­®ì

4^›ŽŽ



—,íîï<
Žðñòó

mBTŠÏh^,Žîç

µòóï`ú¤ÇI2_ï`é18
[11](1~3
μm,q4)。òó£ŸÉÊtà͎åþÐ,oš~
h1gÍMuLîïžgâ

Í#
,“
¥ 

—,
íîï<

q
6)。“


Žíîï<£ŸÉÊî
ö8_â-5wÂíI

q
8)
Ž
PLGA。PLGA
í
îï<ï`¯
189nm,
ç¾BW‚Òh1Ͻ¿j
Žwúfô

muðŠpÉʼ‚hi¿j

o
ð¿jŸ-H

íîï<+ðj88Çöǽ


·348·
2016
y

z ©
41
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}
Vol41,No.5 March,2016

q
10),
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Tet
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q
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°G±{òóŽ¿jSWyª
Tet
/q,Ž±§]ü$G±{à{

q
9),
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Ž/®«íîï<Ž„íÒÓ«[ñí¦·ƒvÒ
Ó

ríîï
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‘

8ù_þ¿—,ï<Ž„íW}
,^
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O

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|}?~

[1] 
±3^

±E

!4

„

¦·q$
CK2
Kô|±hi¿jŸ
 ËJàŽ%&
[J]
$I Ë23-.
,2015,24(6):
719.
[2] 
F:ã

®i

hà‚^,|؎˜™¼½
[J]
K2,-
.
,2005,20(4):185.
[3] ZhangJ,YuB,ZhangXQ,etalTetrandrine,anantihyperten
sivealkaloid,improvesthesleepstateofspontaneouslyhyperten
siverats(SHRs)[J]JEthnopharmacol,2014,151(1):729
[4] HuangP,XuY,WeiR,etalEficacyoftetrandrineonlower
ingintraocularpressureinanimalmodelwithocularhypertension
[J]JGlaucoma,2011,20(3):183
[5] TingCT,LiWC,ChenCY,etalPreventiveandtherapeutic
roleoftraditionalChineseherbalmedicineinhepatocelularcarci
noma[J]JChinMedAssoc,2015,78(3):139
[6] WuK,ZhouM,WuQX,etalTheroleofIGFBP5inmedia
tingtheantiproliferationefectoftetrandrineinhumancolon
cancercels[J]IntJOncol,2015,46(3):1205
[7] LiR,LiX,XieL,etalPreparationandevaluationofPEG
PCLnanoparticlesforlocaltetradrinedelivery[J]IntJPharm,
2009,379(1):158
[8] KreuterJNanoparticles———ahistoricalperspective[J]IntJ
Pharm,2007,331(1):1
[9] GelperinaS,KisichK,IsemanMD,etalThepotentialadvan
tagesofnanoparticledrugdeliverysystemsinchemotherapyoftu
berculosis[J]AmJRespirCritCareMed,2005,172(12):
1487
[10] AlenTM,CulisPRDrugdeliverysystems:enteringthema
instream[J]Science,2004,303(5665):1818
[11] OberdrsterG,OberdrsterE,OberdrsterJNanotoxicology:
anemergingdisciplineevolvingfromstudiesofultrafineparticles
[J]EnvironHealthPerspect,2005,113(7):823

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