Surface Properties of Liposomes Modified with Poly(ethylenimine)

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Polymer (Korea), Vol. 28, No. 6, pp 502-508 (2004)

Vâ, \28Ì \6x, 2004, pp 502-508

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Surface Properties of Liposomes Modified with Poly(ethylenimine)

Yun Jung Park, Da Eun Nam, Dong Hoan Seo, Hee Dong Han, Tae Woo Kim, Moon Suk Kim, and Byung Cheol Shin^%

Advanced Materials Division, KRICT, 100 Jang Dong, Yuseong, Daejeon 305-606, Korea

†e-mail : bcshin@pado.krict.re.kr

(Received July_#16, 2004;accepted November_#16, 2004)

5¨¹ p D Ñ´hq ì,Ü ÔÕ Ä¼\ \DXô $. Ñ´hq ì,Ü 

´hq x, ´ UDpA xÑé ´ ð©´ \$. 8 0¬ éA ´hq x, ´hð©

 X ÈÔ Ñ´hq ì,Ü \°Ô Ã´$. Ñ´hq ì,Ü ¸ 1,2-Tä¼-sn-@ì-3- ,ä,l< (DSPE)< Ñ´hq ÄÐ¸ 4ì8L´< (PEI) 8¼Dø Q©| ©q\ |

Àp \°@$. ì,Ü ´ ´h ùq \ , aU, ¸@$. Ì Hí Xé¡\ ì, Ü Hå (q ¡i ùq ÅÐ ¬p ¼ aU, ¸@$. é é¡ Í\ ì,Ü Uq Hap D, ÅÐ ¬p¼ 7¼ h\ aU@$. Ñ´hq ì,Ü Ì Hí Xé¡

\ Ñ Hå (q´ ¡iX$. ´Ô Hå (q D¼ @ Èô\ Ñ´hq ì,Ü

´< Ø Ùp x´$. Ñ´hq 4ì8L´< ´é ì,Ü ´ U Ì Hí Xé¡ ô

\ (q ¡i Uè$Ô Ã HÌ $. 2, \°\ ì,Ü é é¡ ô\ 7¼

U Ä @p@$.

,-897,.9¹Cationic liposomes for cancer treatment have been developed in the field of chemotharpy. It was well combined on the surface of anionic tumor cell membrane by electrostatic interaction. Thus, the object of this study was to prepare the cationic liposomes capable of forming an ionic complex with the anionic cell membrane.

To prepare the cationic liposomes, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) as a cationic lipid material and polyethylenimine (PEI) as a cationic polymer were synthesized. Ionic property on the surface of liposomes was determined by the zeta potential. The adsorption characteristics of plasma protein for liposome in bovine serum were determined by the particle size and turbidity change. To estimate the stability of liposome in buffered solution, the change of particle size was measured at room temperature for seven days. The cationic liposomes were absorbed a large amount of plasma protein in bovine serum because plasma protein having anionic charge was fixed on the surface of cationic liposomes. This result indicate that the modification on the surface of liposomes using cationic polyethylenimine enhances the protein adsorption in bovine serum.

Additionaly, cationic liposomes showed good stability in buffered solution for seven days.

Keywords¹cationic liposomes, poly(ethylenimine), protein adsorption, stability.

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Polymer (Korea), Vol. 28, No. 6, 2004 Surface Properties of Cationic Liposomes

Vâ, \28Ì \6x, 2004 Ñ´hq ì,Ü ´ ùq# #

¼ øé, Aé X È ôô\ ÀÑé´ Aô

´¼ ´é ½| D,ô 0¬@ \È ÉX ô È$.^2,3ø, ì,Ü|Àp ½| iÜ Ý@, x, ´ Q< é´Ì p D,, ì,Ü

´ $Ñ på @ ÄÐ¼ ð©äÔ 0¬@

ÉXô È$.⁴ 8 Q\ ì,Ü ´ ´hq 8 9 Å, ì,Ü ´< X@ ´h @ |

< ð© é´Ì ¨|¨ ½| D, èh Ò

´Ô 0¬@ \È ÉX È$. ´h| X\

ì,Ü Ñ´h Ø ôÔ ÄÐ d ´(ô ½|

ôXô¨ ´éX È , Ñ´h| X\ ì,Ü

D¼ ÈÔ x,´< UÌ xÑé p x x,´Å`¼ D ôXô¨ SÌ ´éX ô È$.^5,6

8 0¬\Ô Ñ´h Å, ì,Ü ´ U

\ x,´Å`¼ é´Ì p D ôXô¼ $ Ð @$. Ñ´h Åp D X(| ìé\ Ä Ð 600 4ì8L´< ¸ô ìé ýð

A q´ A ½Ì Ì | pÜ` X Èô `Dô D ,é ÄÐ Q Pì éX ÈÔ ÄÐ´$.^7-108 ,Ø PEIÔ é¡ Q ì,Ü ´Q X

p ÀA©p x DSPE PEI¼ ©q, ì é@$. ©q\ DSPE-PEI¼ ´é, ì,Ü ´Q DSPE¼ Å¨|¨ Ñ´hq´ ´ X\

ì,Ü \° Ð @$. ø, ì,Ü ´ ð©

\ PEI Ñ PEI UQ| ð©, UQ U¼ aU¨|¨ U @$. 2, ì,Ü ´ PEI Aå

Ì Hí Xé¡ ô\ ì,Ü Äð é¡

ì,Ü ÅÐ ¬p ¼ aU, Hå ô (q< ì,Ü ¡i ùq @p@$.

51#aU##

Yú1 ì,Ü \°p D, ìé\ \ 1,2- dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), L-a-pho- sphatidylcholine (soy-Hydrogenated) (HSPC), Hä¤

(CHOL), 8ì DSPEÔ Avanti Po lar Lipids Inc. (Ala baster, AL, USA)\ ¬Å, ìé@$. è¸ ½|Ô

qÄ ÈÔ doxorubicin (DOX) Sigma-Aldrich Co.

(Louis, M O, USA)\ ¬Å, ìé@$. \°\ ì, Ü U\p D, l] (MWCO 3,500; Slide-A-Ly zer dialtsis cassette, USA) ìé$. PEI glutaric anhy- dride (GA)Ô Sigma-Aldrich Co. (Louis, MO, USA)\ ¬ Å, ìé@$. ì,Ü ð©\ PEI Ñ @

p D, ìé NHS-fluorescein (5(&6)-carboxyfluo-

rescein N-succinimydyl ester) Sigma-Aldrich Co. (Louis, MO, USA)\ ¬Å, ìé@$. Ì Hí Xé¡ Sigma- Aldrich Co. (L ouis, MO, USA)\ ¬Å, ìé@$. ´

,Ä< 8 , 8´¼´ (MC), N-(3-Dimeth- ylaminopropyl)-N′-ethylcarbodiimidehydrochloride (EDC) 8 ì N-Hydroxy-succinimide (NHS) 1 é$Ô ¼I 2Ô ùI½ ìé@$.

1 ì,Ü \° ìé\ ppÔ ¸ Ä U q D, ÌDÕ Ý\p (Buchi Rotavapor R-200, Swi- tzerland)¼ ìé@ , ì,Ü ÅÐ ¬p °H< (¼

´Q \°¼ D, @Üp (Nort-hern Lipids Ins.)¼ ìé@$. \°Xô ì,Ü ¬p O \ ,

Å Ä]p (ELS-8000, Otus-ka, Japan)¼ ìé@$. ½|

IÅ < ì,Ü ´ ð©\ PEI Ñ UQ Ä Q Q (Barns tead, Apogent Tech, USA)¼ ìé, a U@$. ©q\ DSPE PEIÔ ¹H µ Ðp 5Å ÄQ

(NMR, Bruker, Avance 500)¼ ´é, ¬° Ä] @$.

Ñ´h ì,Ü @ (q ¡i UV-visible ÄQ Q

(UV mini 1240, Shimazu Inc., Japan)¼ ´é, ¡Q

¼ aU@$.

GVSH0SHLÕ#æ®1 DSPE PEI ©q |@, PEI (1 mmol, MW 600)¼ ¥<T% L¼ä¬ c é$ MC 50 mL¼ è@, PEI¼ é´è 10 mL MC é´

è GA (0.01 mmol) é¡ 1 mL/min Í ÜÜÈ è@ h\ 10D X´\ X

\<$. X 20 \ ÌDÕ Ý\p¼ ´é, MC¼ \°@ ´5 89 @ ÈÔ PEI (PEI- co)¼ ©q@$. PEI-co DSPE ©q $< Y

iÕ| É@$. PEI-co (0.83 mmol)¼ EDC (0.83 mmol) NHS (0.83 mmol) 8ì ´,Ä 50 mL¼ Ø

´°\ ¥<T% L¼ä¬ c 30Ä h\

Xä´\ É@$. DSPE (0.83 mmol)¼ ´, Ä 20 mL é´p , X PEI-co@ é´Xô È Ô ¥<T% L¼ä¬ DSPE Xé¡ è@@ 10

D X° Xp$. X 20 \ Ì DÕ Ý\p¼ ´é, ´,Ä è \°@

, èÈÔ DSPE-PEI ©q| ÝX é´è

l] 4 2 \ 72D l] $

, U\@$. l] õ´ U\\ é¡ ð ´

°p ´°, 82% Xh DSPE@ 8¼Dø\ PEI¼

©q@$.

)i#í1 Table 1 ì,Ü @ Å

|© h Ø ô$. ì,Ü Dô Ñ 10 mmol U@ DPPC, CHOL, HSPC, DSPE DSPE- PEI ð h °H, \°@$. AA |

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Park et al. Polymer (Korea), Vol. 28, No. 6, 2004/

UdU# 1# Vâ, \28Ì \6x, 2004/

©, AA CHCI3:CH3OH (2:1 (v/v)) |© é$ é´

è ¥<T% L¼ä¬ c , ÌDÕ Ý\p¼ ´ é, `p é$¼ Ý\\ ´(ô Ç Ä

û$. DOX 17 mmol/mL °´|¨ 10 mmol PBS (Phosphate buffered saline) é é¡ ¹¸ Ä´ U qXô ÈÔ ¥<T% L¼ä¬ |© 60 \ X

¼ p$. X¼ ½| IÅh å D

, freeze-thaw <U 5Ì É@|°, freeze thaw <

U -15, 60 \ AA 7Ä Dé| É @ Ü p (polycarbonate membrane pore size; 100 nm)¼ 50

\ $, ì,Ü ÅÐ ¬p¼ °H@$. ì,Ü

IÅX qÄ< ½| 4 \ 48D

l] (MWCO 3500) É, U\@$.

)iÕ#¹)~#$®#1 PEI X\ ì,Ü Å Ð ¬p ´ ´h q ¸p D, Å Ä]p

¼ ´é, ÅÐ ¬p \ , aU@$. \

°Xô ì,Ü PBS é é¡| ¬] , 25

\ \ ,< ÅÐ ¬p¼ aU@$. ½|

¸ DOX IÅ aU UQ ÄQ Q¼ ìé, TritonX-100 (10%, v/v) è@, ì,Ü Õtè

UQ U Hp UQ U ðU@$.

)i#ÙñM#-æc#SHLÕ##1 ì,Ü ¸À/

ôÀ ´ ð©\ PEI Ñ UQ ÄQ Q¼ ´é

, aU@$. DSPE-PEI (p NHS-fluorescein

ð©\\ NHS-fluorescein UQ U¼ ¡X Lå 490 nm, iÜ Lå 520 nm\ aU@$. PEI ð©\

NHS-fluorescein aU p D´ \°Xô ì,Ü é¡ 2 mL NHS-fluorescein (0.1 mg/mL dimethyl- sulfoxide) 100 µL¼ @ 2D 4 \ X´

\ X \<$. 8 , 0dä l] (MWCO 3500) ìé, 4 \ 48D l] É

@$. l] õ, PEI ð©X NHS-fluorescein \° , UQ ÄQ Q¼ ´é, NHS-fluorescein UQ U¼ aU, ì,Ü ð©\ PEI Ñ

aU@$. ´ ì,Ü ð©Xô ÈÔ Dô PEI

Ñ NHS-fluorescein @p D Triton X-100 (10%, v/v) 20 µL¼ ì,Ü é¡ @, ì,Ü Õtè

NHS-fluorescein< ð© $, aU@$. ì ,Ü ôÀ ð©Xô ÈÔ PEI Ñ Dô ð©\ Ñ

\ ì,Ü ¸À ´ ð©Xô ÈÔ Ñ À R|

ð@$. ì,Ü ð©Xô ÈÔ PEI Ñ NHS- fluorescein À `| ðU@$.

>)#=Ñ#1 Ì Hí Xé¡ ÈÔ ì,Ü

@ Hå(q ¡i Lin89´ 4 iÕ ´é

, É@$.¹¹ ì,Ü< Hå |© é¡ Ô $ <U , É@$. ì,Ü é¡ (1 mL)

< Ì Hí Xé¡ (1 mL) |© , 37 \ Yq

ä° ¼U D Dé| |© é¡ ¼ UV- visible ÄQ Q¼ ´é, 450 nm\ ¡Q¼ a U@$.

)iÕ# #é#=Ñ##Å®1 ì,Ü ÅÐ ¬ pÔ Å Ä]p¼ ´é, aU@$. ì,Ü é¡

(1 mL) Ì Hí Xé¡ (1 mL)< |© , 37 \

Yq@|° ¼U D Dé| |© é¡ ô ì ,Ü ÅÐ ¬p ¼ aU@$. ø, ì,Ü U q ¸p D, \°Xô ì,Ü PBS é é

¡| ¬] , h (25 )\ 4@´\ ÅÐ ¬ p¼ D p¼ aU@$.

61#-y##Ý##

GVSH0SHLÕ#æ®1 PEIÔ é¡ ´p x 

´Q XpÔ ÀA©p x U

 $p D´ DSPE ©q, ´é@$. PEI DSPE

©q\ ¬° Figure 1 Ø ô$. Ø ø T

Y´ ( ©q @Ô°, ëÈ& ©q (\

Ô DSPE ©q X È PEI q 89|

´5 89 Åp D, GA \ õ, © q, ´5 89 Å@$. È& ( PEI-co

´5 89 EDC q è DSPE <

89< X| ©q@$. ( ©q <U|

DSPE PEI ì´ ´ 89´ qX Ã´¼ AXô$.

Figure 2Ô ©q\ PEI-co DSPE-PEI ¹H-NMR a U ð<¼ Ø ô$. PEI-co |¬\ PEI p¸

ùU |¬¸ < 89 |¬¼ 2.5-3.0 ppm\ ¸

@|°, GA p¸ 8L |¬¼ 2.2 ppm\ ¸

¨|¨ ´5 89´ Å\ Ã ¸@$. DSPE- PEI |¬\ PEI ùU |¬$< ¨ DSPE p¸

ùU |¬$´ 0.9, 1.25, 1.6, 2.2, 3.75 ppm\ ¸h

|¨ PEI DSPE@ 8¼DøX ¸@$. © q\ DSPE-PEI¼ ´é, Ñ´h ì,Ü \°

7DEOH 7KH &RPSRVLWLRQ DQG WKH )RUPXODWLRQ RI /L

SRVRPHV0RGLILHGZLWK3(,

Composition M olar Ratio of Formulation liposome DPPC:HSPC:CHOL:DSPE 100:50:30:6 liposome-PEI 10 mol% DPPC:HSPC:CHOL:DSPE-PEI 100:50:30:10 liposome-PEI 20 mol% DPPC:HSPC:CHOL:DSPE-PEI 100:50:30:20 liposome-PEI 30 mol% DPPC:HSPC:CHOL:DSPE-PEI 100:50:30:30

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Vâ, \28Ì \6x, 2004 Ñ´hq ì,Ü ´ ùq# #

@$.

)iÕ#¹)~#®-1#ì,Ü ÅÐ ¬p ´ q

O ½| IÅ Table 2 Ø ô$. \°Xô ì ,Ü ÅÐ ¬p¼ p D, Å Ä]p¼ ´é, ì,Ü ¬p¼ aU@$. è ÅÐ ¬pÔ 140ð160 nm ÔD\ @ph|¨ A ¼ ÅÐ ¬p¼ VÔ ì,Ü´ \°X$. 8ì PEI X\ ì,Ü

´ ´hq 4p D, \ , aU

, ´ D¼ ¸@$. DSPE-PEI ð h Ý@

, \°\ ì,Ü ´ \ , R´ Ý@@$.

DSPE-PEI¼ è@ ì,Ü ° Qq| @p X$. DSPE-PEI¼ è@ ì,Ü ´ D Ñ´h q Ø @p X È , DSPE- PEI ð h

´ Ý@ X Ñ´hq´ Ph Ý@Ô Ã @p

@$. ´Ã Ñ´hq ÄÐ¸ PEI Aå| ì,Ü

´ Ñ´h| X\ Ã Ø ø$. 2, \ ,

´@ Ý@¨ p¼ Ñ´hq´ Ý@h @p X È$. 2, ì,Üô ½|¸ DOX IÅ ¸, ½| D,ô\ @åq ¸@$.

)i#ÙñM#-æc#SHL#Õ#1 ì,Ü ´

PEI@ ð©´ XôÈ ¸p D´ ð©\ PEI Ñ

N O

H H

H P O

O O

O O H

O

O DSPE H2N N

H H

N N H

N NH₂

NH₂

x y m

PEI (MW 600)

O

O O

H₂N N H

H

N N H

N NH

NH₂

x y m

C O

C OH O

H₂N N H

H

N N H

N NH

NH₂

x y m

C O

N O

H

H P O

O O

O O H

O

O CH₂Cl₂

EDC, NHS, CHCl3

)LJXUH Synthesis of DSPE-PEI./

a C

O

C OH O PEI

a b

b

d e

k f C

O C O

N O

H

H P O

O O

O O H

O

PEI d

d f e

h k

-0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0

h

a C

O

C OH O PEI

a b

C O

C OH O PEI

a b

b

d e

k f C

O C O

N O

H

H P O

O O

O O H

O

PEI d

d f e

h k

C O

N O

H

H P O

O O

O O H

O

PEI d

d f e

h k

-0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0

-0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0

-0.5 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0

h

/

)LJXUH  ¹H-NMR spectrum of the synthesis DSPE-PEI in CDCl3./

7DEOH3\VLFDO3URSHUWLHVRI/LSRVRPHV0RGLILHGZLWK

3(,0HDVXUHGLQ3%6EXIIHUHG6ROXWLRQDW5RRP7HP

SHUDWXUHDVD)XQFWLRQRIPRORI3(, D iam eter

(nm ) Poly- dispersity

Zeta Potential (m V )

M obility (cm 2/V s,10^-5)

D O X Loading Efficiency(% ) liposom e 141 2.8 0.14 0.10 67.5 liposom e-PEI 10

m ol% 164 2.2 5.16 4.09 53.7 liposom e-PEI 20

m ol% 160 1.9 11.62 9.22 35.2 liposom e-PEI 30

m ol% 141 1.6 16.65 13.23 38.5

813# 718# 713# 618# 613# 518# 513# 418# 413# 318# 313# 0318#

#;13# :18# :13# 918# 913# 818#

#;13# :18# :13# 918# 913# 818# 813# 718# 713# 618# 613# 518# 513# 418# 413# 318# 313#0318#

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UdU# 1# Vâ, \28Ì \6x, 2004/

aU@$. ì,Ü ´ ð©\ PEI Ñ PEI

<p ð©\ NHS-fluorescein UQ U¼ aU, ðU@$. DSPE-PEIÔ (p <p¼ Èô NHS-fluorescein< ð© X ÈÔ ¬°¼ @ È$.

Table 3 PEI Í p¸ ì,Ü ´ ð©Ô PEI

Ñ Ø ô$. ì,Ü \° ì,Ü-PEI 10 mol%

@ ýð ¸À 0.25 mg/mL ì,Ü Ñ| PEI@

X È$. p¼\ ì,Ü ¸À ´ ´ D@ Ñ´

hq| Ý@XÔ Ã @p@$. 8ì ð h´

Ý@¼ Dô ì,Ü ´Ô ÷ Ñ PEI@

° c ÄÐ Ñ´ $´¼ ì,Ü ´

\ Dô ÄÐ Ñ \ ÷$ @$.¹² )iÕ#>)#=Ñ1 ì,Ü Ì Hí Xé¡ ô\

Hå (q ¡i @pp D iÕ| ì,Ü<

¡Q@ \\È Ý@@$. 7D ´ ¡Q@

° -| Ý@Ô Ã < X È , PEI Ñ´ Ý@

X ¡Q@ ¬Ì Ø ô$. PEIÔ Hå (q

< ì,Ü ´ ì´ (q ¡i Ý@äp x

ì,Ü´ ,¨Xô ÈÔ Ì Hí Xé¡ ¼ Ý@

äÔ° p,¨ X È$. ¨ ì, Ü´ (q ¡i Aå <Ô Ã Liu 89< Mercadal 89 , 4 X$.^13,14 Ô Hå (q´ ì, Ü ´ ¡i` Ý@@$. ´ ð<Àp ì,

Ü ´ (q ¡i PEI ´ Ñ´h| XX ô\ ´hq (q$´ ´ Ùp x (q ¡i

´ Ý@\$Ô Ã X È$. ì,Ü ´ (q

¡i x, ¡iq P(p D QÔ Ô¸

| Ñé$.

)iÕ# #é#=Ñ1 Lin 89 Ì Hí Xé¡

\ ÅÐ ¬p @ ì,Ü ÈÔ Hå (q ¡i<

@h´ È$Ô Ã 4 @$.¹¹ì,Ü Hå (q ¡ i @pp D iÕ| ÅÐ ¬p ¼ @p@

$. ì,Ü´ ,¨Xô ÈÔ Ì Hí Xé¡ (q ¡ i 37 \ ÅÐ ¬p ¼ aU, ðU@

$. Figure 4 Ì Hí Xé¡ 4@Ô D

p¼ XÔ ì,Ü ÅÐ ¬p¼ Ø ô$. @

A| p D, Hp ÅÐ ¬p¼ 100 nm p@

| @$. ì,Ü ÅÐ ¬pÔ 48D Ì Hí Xé¡ 4@Ô 100\ 700 nm ´ Ý

@@$. PEI ð h Ý@° \°\ ì,Ü Å Ð ¬p@ 900, 1000, 1100 nm´| Ý@@$.

ÅÐ ¬p ¨ PEI Ñ´ Ý@ X

ÅÐ ¬p@ ñ $ Ô Ã ¸ X È$. p¼\

ì,Ü ÅÐ ´´ Ñ´h Ø ü ýð Håô

´hq (q< ¡i´ é´Ì ¼ôÜ$Ô Ã @p

@$. 8, Ñ´hq ì,Ü U%<ì éX 7DEOH$PRXQWRIWKH3(,RQWKH,QQHU2XWHU6XUIDFHRI/LSRVRPHV

Liposome Initial Concentration of PEI (mg/mL Liposome)

Inner Surface (mg/mL Liposome)

Outer Surface (mg/mL Liposome)

Total PEI (mg/mL Liposome)

PEI 10 mol% 0.7 0.33 0.14 0.47

PEI 20 mol% 1.4 0.17 0.25 0.42

PEI 30 mol% 2.1 0.14 0.29 0.43

)LJXUH Turbidity change with time in bovine serum containing liposomes at 37×liposome (\), liposome-PEI 10 mol% (;), liposome-PEI 20 mol% (5), liposome-PEI 30 mol% (`)./

3# 43# 53# 63# 73# 83#

Time (hour)

Optical density at 450 nm

419 417 415 413 31;

319 317

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Vâ, \28Ì \6x, 2004 Ñ´hq ì,Ü ´ ùq# #

p4$Ô ùU ÀD `A| <ì X ÈÔ ÀA <ì\\\ é´ @å$.

Á&#&Þ#M#)iÕ#Å®#1 PEI X\

ì,Ü Ðô Uq 4p D, é é¡ô ì ,Ü h (25 )\ 7¼ D p¸ ÅÐ ¬p

¼ aU, Figure 5 Ø ô$. @A| p D, Hp ÅÐ ¬p¼ 100 nm p@| @$. ì, Ü ÅÐ ¬pÔ D p¼\ ¼U Ã @p@

$. Ñ´hq Ø ô Ô ì,Ü ÅÐ ¬p@

¨´ ´ U X´ DSPE-PEI@ è@\ Ñ´hq ì,Ü ÅÐ ¬pÔ Hp 6D Ô $Ì Ý@

@|Ø 6D ´Ô ì,Ü ¬p@ ¨´ ¼U

@ , ´ ì,Ü Ðô ÕtØ 1 @ @ pX $. p¼\ Ñ´hq ì,Ü h\

A U$ Ha X È$.

71#-Ý##

8 0¬\Ô Ñ´hq ì,Ü \°p D,

´hq ì,Ü Håô (q ¡i ùq @p@

$. DSPE-PEI è@ ¸, ì,Ü ´ Ñ´h q È ¸@ \°Xô ì,Ü

¸@$. ì,Ü ,¨ Ì Hí Xé¡\ ì, Ü ÅÐ ¬p, Ô PEI è@ h´ Ý@

X Ý@Ô Ã @p@$. 2 ½| IÅ

, \°\ ì,Ü h\ A U$ Ha X È$. 8 0¬Ô ì,Ü ½| IÅ, Ñ´h V ´ qè ½| D,ô @

Ã|¨ ùU¸ôÀD Q <ì, ½|

è<¼ Ýì X ÈÔ ½|D,ô \° @ p 8A¸ Ð é` Ã´$.

\ì< U4õ 0¬¥ IMT-2000 Ü0H p`\\

ì| ´(ô Ã| ´ Pìý$.

Uhihuhqfhv##

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)LJXUH The particles size distribution with time in bovine serum at 37 ×liposome (\), liposome-PEI 10 mol% (;), liposome-PEI 20 mol% (5), liposome-PEI 30 mol% (`)./

# 3# 43# 53# 63# 73# 83#

Time (hour)

Liposome size (nm)

4533 4333

;33 933 733 533

)LJXUH The estimation for stability of liposome via the particle size in buffered solution at room temperature : liposome (\), liposome-PEI 10 mol% (;), liposome-PEI 20 mol% (5), liposome-PEI 30 mol% (`)./

# 3# 53# 73# 93# ;3#

Time (hour)

Liposome size (nm)

633

533

433

(7)

UdU# 1# Vâ, \28Ì \6x, 2004/

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Surface Properties of Liposomes Modified with Poly(ethylenimine)

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Surface Properties of Liposomes Modified with Poly(ethylenimine)

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