3 543-548 owXXXXXXXXXXXX~ XXXXXXXX8XX

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Polymer(Korea), Vol. 29, No. 6, pp 543-548, 2005 543 1.# g«# Ó ZB 2ú²® ÿW ' ÖZ& þRW² Ó ZB ®6 N þRÒ OVª2²¾ '®"& Þr Ó ²W ª®êÆ ÞÆ ÊÒ ZÊ, J: kWÊ6 þRWÎ Ó rr ® Z² FÂV ²rÞ ß gÊ:. 1-12 Ó® ò rê Ó ZB 2ú²® ² WCÎ ûÿ ª[® Gû² rZ®â n :. 5 Ó® ò rÒ Z² ë²¾ òÿ Ó 6Úæ & îÎÂ² Ú2r ²ÊW óV2úÆî, Ó® ÿÊ e 3 Êÿ¶ óV2úê 6 Ú, 2,4,8 jÂk, e k f ê ® ÿæ g& :Î ÚæV ®BNÎ 6k K¿Î Bg K¿ , 1,3,5,6,9 N6 nÿ R G& 10 V² FÂV ²rÞ ß gÊ:. Ê ë: òÿ Ó® ÿÊÒ óV2r Vÿª~ óV2 úÆ VÖÚ ÃÖ û lÆî ò rÒ ¶ n Þê ûf R2Z#¬#9)³´#ì#SOJD\#kR_ûÌ#ìºQ#¨#§# +Ð'}¿÷S}¿ã}+<( }lgb }Sh }`k }¿ÐS}¿¿t # DÁ(# ÄÐZØ¸5</# DÁ(# 5^</# # è(# ÄÐ5</# -^¬# Ø¸ôì¬# +5338#5#6¼# Q:/#5338#<# 5;¼# ,# # Ideulfdwlrq#ri#SOJD2Gh{wudq#Grxeoh0Od|huhg#Plfurvskhuhv#e|## Rlo0lq0Zdwhu#Vroyhqw#Hydsrudwlrq#Phwkrg# Mrqj#Wdh#Nr/#Mdh0Kr#Ohh/#Fkdqj0Udh#Ohh/#K|xqj#Vln#Vklq*/#Vrrq#Krqj#\xn**/# # Prrq#Vxn#Nlp***/#Jlovrq#Nkdqj /#Mrkq#P1#Ukhh/#dqg#Kdl#Edqj#Ohh*** Department of Polymer¯Nano Science and Technology, Chonbuk National University, 664-14, Dukjin, Jeonju 561-756, Korea *Department of Chemical Engineering, Chonbuk National University, 664-14, Dukjin, Jeonju 561-756, Korea **Department of Polymer Science and Engineering, Hannam University, 133, Ojeongdong, Daedeog, Daejeon 306-791, Korea ***Nanobiomaterials Laboratories, Korea Research Institute of Chemical Technology, P. O. Box 107, Yuseong, Daejeon 305-506, Korea (Received August 3, 2005;accepted September 28, 2005) 5¨Ü Êg NÂê >Ò NÂ& Êr ^ òR Ãâ û, e Ó ò r G® ûf l6 Þ:. NBî Bg 3Ê ¢:Ã6 2> Ê® rÆ RkÊ ê®Æ Þ NÂ rÆ 2 Â Æ^Ê :ê >f l6 Þ:. Òr N FÂ&rê ÓÊ2V²ÒÊ2 Kg¿(PLGA) ÇúÖ® r² :Î 6 ÚæÒ ^6Rb Ú v& Î ngvk(O/W) ÿ: órë Êÿ®B Êg NÂÒ rÆ®V:. f² PLGA® ã& Ò NÂ Â® ªÒ FÂ®V:. Êg NÂê ZæRZN, /^f kg ^ÊVZN(CFLM), öúªZÒ Êÿ®B Æ®V:. rÆr Êg NÂ® ÎÖÊ :B Âk® k2Ò î «Î¶ n Þ Æ, ^>2 ÖR ÎÖ® k2Ò «:Þ ÂÚ¶ n Þ:. Ê& ÎÖR Ö® Â «Î®6 æ b>zÊ6-5-Êâ2zÊ-ÇúÖ(FITC-ÇúÖ) ÊÿÊ CFLM V² R kg ¶ê ÇúÖ² Âr ÖR kg ¶ ê PLGA ÎÖ V®V:. f² PLGA® ¾& Î NÂ® Âê ZW ² óV®ê û «Î®V:. Ê o R²Ö ¦W Z>² ngvk ÿ: órë Êÿ®B PLGA Ç úÖ® Êg NÂ® rÆV Vû¾ «Î¶ n Þ:. Abstract: Double-layered spheres play an important role in controlling drug delivery for pharmaceutical application, because of the low initial burst compared with single-layered spheres and targetable delivery to specific organ. But it has drawback in loading drug and controlling size. In this study, we developed double-layered spheres using relatively simple oil-in-water (O/W) solvent evaporation method with/without ultrasonication and investigated the size variation of the double-layered microspheres on the contents of poly(lactide-co-glycolide) (PLGA). Double-layered spheres were char- acterized by scanning elecron microscope (SEM), camscope, and confocal fluorescence laser microscope (CFLM). Dou- ble-layered spheres showed smooth surfaces and obvious difference between core and corona by SEM observation and camscope. We observed the fluorescent core in the double-walled spheres composed of FITC-dextran and PLGA using CFLM. It was found that the core of the microsphere was dextran and the corona of the fabricate microsphere was PLGA. Also, the more PLGA concentration, the more the size of the fabricating double-layered sphere observed. Keywords: double-layered microspheres, PLGA, dextran, O/W, ultrasonication. † To whom correspondence should be addressed. E-mail: [email protected]. kr

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Page 1: 3 543-548 owXXXXXXXXXXXX~ XXXXXXXX8XX

Demo

Polymer(Korea), Vol. 29, No. 6, pp 543-548, 2005

543�

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Department of Polymer�Nano Science and Technology, Chonbuk National University, 664-14, Dukjin, Jeonju 561-756, Korea

*Department of Chemical Engineering, Chonbuk National University, 664-14, Dukjin, Jeonju 561-756, Korea

**Department of Polymer Science and Engineering, Hannam University, 133, Ojeongdong, Daedeog, Daejeon 306-791, Korea

***Nanobiomaterials Laboratories, Korea Research Institute of Chemical Technology, P. O. Box 107, Yuseong, Daejeon 305-506, Korea

(Received August 3, 2005;accepted September 28, 2005)�

�� , � ��

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�� (O/W) �� . �� PLGA�

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�� . ��

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Abstract:�Double-layered spheres play an important role in controlling drug delivery for pharmaceutical application,

because of the low initial burst compared with single-layered spheres and targetable delivery to specific organ. But it has

drawback in loading drug and controlling size. In this study, we developed double-layered spheres using relatively simple

oil-in-water (O/W) solvent evaporation method with/without ultrasonication and investigated the size variation of the

double-layered microspheres on the contents of poly(lactide-co-glycolide) (PLGA). Double-layered spheres were char-

acterized by scanning elecron microscope (SEM), camscope, and confocal fluorescence laser microscope (CFLM). Dou-

ble-layered spheres showed smooth surfaces and obvious difference between core and corona by SEM observation and

camscope. We observed the fluorescent core in the double-walled spheres composed of FITC-dextran and PLGA using

CFLM. It was found that the core of the microsphere was dextran and the corona of the fabricate microsphere was PLGA.

Also, the more PLGA concentration, the more the size of the fabricating double-layered sphere observed.

Keywords: double-layered microspheres, PLGA, dextran, O/W, ultrasonication.

†To whom correspondence should be addressed. E-mail: [email protected]

Page 2: 3 543-548 owXXXXXXXXXXXX~ XXXXXXXX8XX

544� ��

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�� .11,12

��

��

� �� (water-in-oil-in-water, W/

O/W � oil-in-oil-in-water, O/O/W)� ��

�(oil-in-oil, O/O) �� (water-in-oil, W/O)� ��

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� ��

��(coaxial ultrasonic atomizer)� ��

� ��.3,6,11-16 ��

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�� PLGA� ��

� �� O/W �� . ��

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�� PLGA� �� 10, 30, 50, 100, 150, �

300 w/w%� �� . ��

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��(CLFM) ��

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�� (scanning electron microscope, SEM)�� .

2. ��

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�� 43000 g/mol� Sigma Chem. Co. Ltd.�(St. Louis,

Mo, USA)�� . PLGA� �� 90000 g/mol

� RESOMER RG 752(��/�� , 75/25, Boehringer

Ingelheim Chem. Co. Ltd., Manheim, Germany) ��

��. �� (�� )(PVA)�

�� 1500 g/mol� Showa Chem Co. Ltd.(Tokyo, Japan) ��

��. CLFM �� 5-�� -

��(FITC-dextran)� �� 40000 g/mol� Sigma Chem. Co.�

�� . ��(DCM)� Merck. Co(Menheim,

Germany)�� .

2.2 ��

� �� PLGA� � � �� Figure

1(a) � (b)�� CLFM� �� FITC� ��

�� (c)� ��. ��

�� Table 1� ��. �� Figure

2(a)�� O/W �� . � 50 mL� ��

�� 1.5 g� PVA � 0.5 g� ��

�� 5 mL� DCM� 10, 30, 50, 100, 150, � 300 w/w%�

PLGA� ��

�� 7�� Figure

2(b) �� 50 mL� �� 1.5 g� �� PVA � 0.5 g�

�

(a)

OH

OH OH

H

H

OH

OH

CH2

H

n

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(b)�

O

OHHO

O

O

NCS

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(c)

Figure 1. Chemical structures; (a) PLGA, (b) dextran, and (c) Fluorescein 5-isocyanate (FITC).

Table 1. Preparation Conditions of Double-Layered Microsphere in Simple Mechanical Method with/without Ultrasonication

PLGA(g) DCM(mL) Dextran(g) PVA(g) Water(mL)

0.05(10%) 5 0.5 1.5(300%) 50

0.15(30%) 5 0.5 1.5(300%) 50

0.25(50%) 5 0.5 1.5(300%) 50

0.50(100%) 5 0.5 1.5(300%) 50

0.75(150%) 5 0.5 1.5(300%) 50

1.50(300%) 5 0.5 1.5(300%) 50

Page 3: 3 543-548 owXXXXXXXXXXXX~ XXXXXXXX8XX

O/W �� PLGA �� 545�

Polymer(Korea), Vol. 29, No. 6, 2005�

�� 5 mL� DCM�

10, 30, 50, 100, 150, � 300 w/w%� PLGA� ��

�� 7�� . �

�� RZR 2102(Heidolph Instrument Gmbh

& Co. KG, Schwabach, Germany)� �� 300

rpm�� . �� ultrasonic dismembrator model 500

(Fisher Scientific, USA)� �� 30%�� 30�� .

� � �� 2000 rpm�� 4��

��

5�� . ��

�� 56 � 80 mtorr ��

��.

2.3 ��

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(Camscope, Model SV-32, Sometech, Korea)� �� 300� ��

� �� IT PRO(Sometech, Korea)� ��

��.

2.4 ��

�� SEM

(model s-2250N, Hitachi Co., Tokyo, Japan)�� (ACC voltage)

15 kV�� 60, 500, � 800 ��

�� . � �

�� SEM ��

(Emiteck, K575, UK)� ��

�� .

2.5 � ��

�� PLGA� ��

� �� CFLM� ��. ��

�� CFLM �� FITC-��

�� . � ��

� �� 200 ��

��.

3. ��

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� Table 2 Figures 3 � 4� ��. � ��, PLGA�

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�� O/W ��

�� PLGA� DCM�

��

� � DCM� ��

� �� O/W �� PLGA� DCM�

Table 2. Characteristics of Double-Layered Microsphere in Simple Mechanical Method with/without Ultrasonication

Batch PLGA conc. Transparency(T) Spheres size

no. (g(w/v%)) or opacity(O) ��

SM-1% 0.05(10%) T less than 5~91

SM-3% 0.15(30%) T 12�162

SM-5% 0.25(50%) T 30�189

SM-10% 0.50(100%) T 39�267

SM-15% 0.75(150%) T 52�487

SM-30% 1.50(300%) T over 100~1000

UM-1% 0.05(10%) O 91 and less

UM-3% 0.15(30%) O 10 and less�130

UM-5% 0.25(50%) O 10 and less�150

UM-10% 0.50(100%) O 10 and less�411

UM-15% 0.75(150%) O 10 and less�486

UM-30% 1.50(300%) O 10 and less�586

SM-simple mechanical stirring. UM-mechanical stirring after ultrasonication.

�

(a)

��

��

��

��

��

(b)

Figure 2. Schematic diagram of fabrication method for the double-layered microsphere of PLGA and dextran using O/W solvent evaporation method; (a) simple mechanical stirring and (b) mechanical stirring after ultrasonic-cation.

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Page 4: 3 543-548 owXXXXXXXXXXXX~ XXXXXXXX8XX

546� ��

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� �� DCM� ��

� � DCM� �� PLGA� �� ,

�� .3 O/W

��

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�� PLGA� ��

�� PLGA ��

� ��

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3.2 ��

�� O/W ��

�� PLGA �� SEM� ��

�� Figure 5� ��. Figure 5(a)��

�� . �� Figure 5

(b)��

��. �� PLGA� ��

� ��. �� O/W��

PLGA �� .

3.3 � ��

�� SEM� ��

�� FITC� ��

�� CFLM� ��. Figure 6� (a), (b), � (c)� �

��

�� CFLM � ��. Figure 6(a)� ��

�� FITC� �� (b)��

� �� . (b)��

�� PLGA� ��

�� . Figure 7 (a),

(b), � (c)� ��

� �� CFLM � ��. Figure 6(a)� � ��

Figure 7(a)��

�� PLGA ��

��. ��

��

�� Figure 6�� Figure 7� ��

� ��

��

� �� .

��

�� Figure 3. The morphology observation of double-layered microspheres with variation of PLGA concentration using camscope(�300) (simple mecha-nical stirring method).

��

�� Figure 4. The morphology observation of double-layered microspheres with variation of PLGA concentration using camscope(�300) (mechanical stirring after ultrasonication).

outer shell inner shell

� � �

(a) �60

� � �

(b) �500

� � �

(c) �800

Figure 5. Surface characterization of the outer shell (PLGA) and inner shell (dextran) of the double-layered microsphere of PLGA and dextran using O/W solvent evaporation method; (a) �60, (b) �500, (c) �800.

Page 5: 3 543-548 owXXXXXXXXXXXX~ XXXXXXXX8XX

O/W �� PLGA �� 547�

Polymer(Korea), Vol. 29, No. 6, 2005�

4. ��

�� PLGA ��

�� O/W ��

�� W/O/W ��

� �� . �

� ��, SEM ��

��

��

�� . �� FITC� ��

�� CFLM ��

�� PLGA ��

��. �� PLGA� ��

� ��

� ��

��. � ��

�� PLGA� ��

��/��

��.

�� PLGA ��

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�� (2004-01352, 2004-00274)� ��

�� .

��

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loaded PLGA microspheres for long acting anesthesia”, in Controlled

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� � � � � � � � � � � �

��

��

� (a) (b) (c)

Figure 6. Confocal laser microscope images of double-layered microsphere fabricated using simple mechanical stirrer method without ultraso-nication(�200); (a) fluorescence image, (b) non fluorescence image, and (c) merged image of (a) and (b).

� � � � � � � � � � �

��

��

� (a) (b) (c)

Figure 7. Confocal laser microscope images of double-layered microsphere fabricated using mechanical stirrer method with ultrasonication(�200); (a) fluorescence image, (b) non fluorescence image, and (c) merged image of (a) and (b).

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548� ��

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DigitalHeritage2013 Submission 548

9-6 Notes pp.543-548 7th period.notebook - Mr. D's Sitemderocher.weebly.com/uploads/4/0/0/.../9-6_notes_pp.543-548_7th_… · probabilities Of winning each game. The probability of

9-6 Notes pp.543-548 7th period.notebook - Mr. D's Sitemderocher.weebly.com/uploads/4/0/0/.../9-6_notes_pp.543-548_7th_… · probabilities Of winning each game. The probability of

Computer Graphics 543 Lecture 3): Fractalsemmanuel/courses/cs543/f13/slides/lecture02_p3.pdf · Computer Graphics 543 Lecture 2(Part 3): Fractals Prof Emmanuel Agu Computer Science

Computer Graphics 543 Lecture 3): Fractalsemmanuel/courses/cs543/f13/slides/lecture02_p3.pdf · Computer Graphics 543 Lecture 2(Part 3): Fractals Prof Emmanuel Agu Computer Science

akppgid.ru TRANSMISSION SERVICE GROUP 77 Technical Service Information 535 545 544 543 542 541 540 539 546 538 548 537 547 536 Figure 150 FRONT PLANET CARRIER AND SUN GEAR ASSEMBLY

akppgid.ru TRANSMISSION SERVICE GROUP 77 Technical Service Information 535 545 544 543 542 541 540 539 546 538 548 537 547 536 Figure 150 FRONT PLANET CARRIER AND SUN GEAR ASSEMBLY

Snippetz_Issue 543

Snippetz_Issue 543

SA Möbler AB | Kyrkefallavägen 3 | 543 34 Tibro | Sweden ...

SA Möbler AB | Kyrkefallavägen 3 | 543 34 Tibro | Sweden ...

543 Presentation

543 Presentation

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