ADI EISENBERG - McGill Universitycsacs.mcgill.ca/.../docs/activities/classes/2007-class-eisenberg.pdf · adi eisenberg. nice to see you again. outline introduction (brief review of

BLOCK COPOLYMER

VESICLES

UNIVERSITY OF BAYREUTHTUESDAY, JUNE 13, 2006

ADI EISENBERG

NICE TO SEE YOU AGAIN

OUTLINEINTRODUCTION (BRIEF REVIEW OF FIRST LECTURE)

SMALL MOLECULE AMPHIPHILES AND DIBLOCK COPOLYMERSMETHODS OF PREPARATIONACCESSIBLE MORPHOLOGIESTHERMO, KINETICS AND MORPHOLOGICAL CONTROL MECHANISMS

VESICLES, PREPARATION AND THERMODYNAMICSTYPES OF VESICLESTHERMODYNAMIC CURVATURE STABILIZATIONCONTROL OF INTERFACIAL COMPOSITIONINVERSIONEQUILIBRIUM CONTROL OF SIZESTRIGGERS FOR MORPHOLOGICAL AND DIMENSIONAL CHANGES

(IONS, SURFACTANTANTS, WATER…)KINETICS AND MECHANISMS OF SIZE CHANGES

VESICLES, FILLING AND NON-DESTRUCTIVE RELEASEFILLING OF ACTIVE INGREDIENTS (DOX)DIFFUSIONAL RELEASE OF CONTENTS (DOX)DIFFUSION OF PROTONS THROUGH VESICLE WALLS

CONCLUSIONS

BLOCK AND GRAFT COPOLYMERS

AB Diblock

ABA

BAB

Tapered block

Graft

Triblock

Alternating block

A sodium dodecylsulfate (SDS) micelle model (n=60) drawn to scale. After Israelachvili

Star Micelle

(PS23-b-PANa2400)

“Crew-cut” Micelle

(PS420-b-PANa46)1 :100 10:1

Morphologies of Block Copolymers in Aqueous SolutionsMorphologies of Block Copolymers in Aqueous Solutions

201

Vesicle

Morphologies of Block Copolymers in Aqueous SolutionsMorphologies of Block Copolymers in Aqueous Solutions(Continued)(Continued)

Lamella

NEXT: PREP. AND MORPH.

PREPARATIVE METHODS (1)

TEMPERATURE QUENCH AND FREEZE-DRY EQUILIBRATED SOLUTIONS

Add water to polymer solution in dioxaneAt predetermined water concentration, drop temperature to near - liquid N2

Warm under vacuum to sublime off dioxane and water.

WATER QUENCH EQUILIBRATED SOLUTION AND DIALYZE

Add water to polymer solutionAt predetermined water concentration, quench into waterDialyze

Spherical micelles

PS(200)-b-PAA(21)

Lamellae

PS(49)-b-PAA(10)

HHH

PS(410)-b-PAA(13)LCM

PS(200)-b-PAA(4)

Vesicles

PS(410)-b-PAA(13)

Rods

PS(190)-b-PAA(20)

Bicontinuous Rods

PS(190)-b-PAA(20)

Lamellae

PS(132)-b-PAA(20)

Cameron, N. S.; Corbierre, M. K.; Eisenberg, A. Can. J. Chem. 1999, 77, 1311.

THERMODYNAMICS OF FORMATIONOF CREW-CUT AGGREGATES

“MORPHOGENIC” CONTRIBUTIONS TO ΔG

1. CHAIN STRETCHING IN CORE2. REPULSION AMONG CORONA CHAINS3. INTERFACIAL ENERGY

LOW WATERCONTENT

HIGHWATERCONTENT

1. INTERFACIAL ENERGY INCREASES2. TOTAL INTERFACIAL AREA DECREASES3. CORE RADIUS INCREASES4. NUMBER OF MICELLES DECREASES5. CORE CHAINS ARE STRETCHED6. DISTANCE BETWEEN CORONA CHAINS

DECREASES7. CORONA CHAIN REPULSION INCREASES8. MORPHOLOGY CHANGES AT SOME

CRITICAL POINTS

FOR EXAMPLE: AS WATER IS ADDED

MORPHOLOGY CHANGES CAN BE INDUCED BY CHANGES IN ANY OF THE THREE

PARAMETERS BY DIFFERENT CONTROL MECHANISMS

RELATIVE BLOCK LENGTHS

WATER CONTENT

COPOLYMER CONCENTRATION

ADDED IONS, pH

NATURE OF COMMON SOLVENT

HOMOPOLYSTYRENE

TEMPERATURE

SURFACTANTS

POLYDISPERSITY

Phase Diagram of Fractionated PS310-b-PAA52 in Dioxane/H2O

Water Content (wt%)

0 5 10 15 20 25 30 35 40 45

Cop

olym

er C

once

ntra

tion

(wt%

)

0.1

1

10

Water Content (wt%)0 5 10 15 20 25 30 35 40 45 50

Copolymer (wt%

)

05

10

Diox

ane (

wt%

)

9095

100

S R R + V VS + R

Hongwei Shen & Adi Eisenberg, J. Phys. Chem. B 1999, 103, 9473

Now: Vesicles

TYPES OF VESICLES

small uniform vesicleslarge polydispersevesicles

entrapped vesicles

hollow concentric vesicles

onions

tube-walled vesicles

500 nm

100 nm

200 nm

PS410-b-PAA13 PS100-b-PEO30 PS200-b-PAA20

PS100-b-PEO30PS260-b-P4VPDecI70PS132-b-PAA20

Original references given in S. Burke and A. Eisenberg Macromolecular Symposia (Warsaw IUPAC meeting)

500 nm

THEMODYNAMICALLY STABLE VESICLESARE PRODUCED BY WORKING IN

LARGE REGION OF THE PHASE DIAGRAMWHERE VESICLES ARE THE ONLY

(OR THE DOMINANT)MORPHOLOGY

SIZES, WALL THICKNESS AND INTERFACE COMPOSITION CAN BE CONTROLLED

BY FINE TUNING THE DETAILEDPREPARATIVE CONDITIONS

(WATER CONTENT, SOLVENT COMPOSITION, pH, IONIC STRENGTH, ETC.)

ARE VESICLES EQUILIBRIUM STRUCTURES? WHAT ARE KINETICS AND MECHANISMS OF FORMATION AND TRANSFORMATION?CURVATURE STABILIZATION MECHANISM?PROOF OF SEGREGATION USING LABELED BLOCK COPOLYMERS IS SEGREGATION SIZE DEPENDENT? IS SEGREGATION REVERSIBLE? ARE SIZES CONTROLLABLE?ARE SIZE CHANGES REVERSIBLE?

QUESTIONS ABOUT VESICLES (1)

CAN DIFFERENT GROUPS BE ATTACHED INSIDE AND OUTSIDE?CAN VESICLES BE INVERTED?HOW FAST DO VESICLES FUSE? WHAT IS THE EQUILIBRATION MECHANISM?CAN WALL THICKNESS BE CONTROLLED?CAN VESICLES BE FILLED? CAN WALLS BE PLASTICIZED? CAN PROTONS DIFFUSE THROUGH WALLS?

QUESTIONS ABOUT VESICLES (2)

Water Content (wt%)

0 10 20 30 40

Turb

idity

0.0

0.5

1.0

1.5

2.0

Water Addition

Dioxane AdditionMicellization

Spheres to rods

Rods to Vesicles

Changes in Aggregate Morphology Are Associated With Changes in Turbidity

PS310-b-PAA52 1% w/w in dioxane

Shen, H.; Eisenberg, A. J. Phys. Chem. B. 1999, 103, 9473-9487

Time (sec)

0 200 400 600 800 1000

Turb

idity

0.8

0.9

1.0

1.1

1.2

1.3

1.4

26.4 - 27.7 wt%

26.2 - 28.8 wt%

Turbidity Increase With Time After 1% Water Jump

PS310-b-PAA52 1% w/w in dioxane

Chen, L.; Shen, H.; Eisenberg, A. J. Phys. Chem. B. 1999, 103, 9488-9497

0 sec


Time (sec)

0 500 1000 1500 2000

Turb

idity

0.6

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

((Tca

l. - T

exp.

)/Tex

p.) (

%)

-4

-2

0

2

4

6

8

10

12

DCBADouble Exponential Fit

Single Exponential Fit

Experimental Curve

Fitting Quality


y = y0 + a(1 – exp(–k1*t)) + b(1 – exp(–k2*t))

y = y0 + a(1 – exp(–k1*t))

Concentration of Each Species

⎥⎦

⎤⎢⎣

⎡+−

−+−

−−=

⎥⎦

⎤⎢⎣

⎡+−

−

−+−

−

−−=

⎥⎦

⎤⎢⎣

⎡+−

−

−++−

−

−+−=

21

212

122

211

121

210

21

212

122

2211

121

1210

21

212

122

2121211

121

2111210

)exp()(

)exp()(

)exp()()(

)exp()()(

)exp()(

)exp()(

mmkk

tmmmm

kktm

mmmkk

CC

mmkktm

mmmmkk

tmmmmmkk

CC

mmkktm

mmmmmmkkk

tmmmm

mmmkkkCC

ffffffrvt

bbbfbfrlt

bbfbbfbbrrt

m1 and m2 stand for:

[ ]

[ ])(4)()(21

)(4)()(21

2121212

221122112

2121212

221122111

ffbfbbbfbfbfbf

ffbfbbbfbfbfbf

kkkkkkkkkkkkkkm

kkkkkkkkkkkkkkm

++−+++++++=

++−+++−+++=

Time (sec)

0 200 400 600 800 1000 1200 1400 1600 1800 2000

C/C

r0

0.0

0.5

1.0

1.5

Vesicle

Lamella

Rod


Concentration of Each Species

Next: Curvature stabilization mechanism

Transmission electron micrograph (TEM) of vesicles of PS300-b-PAA44

Quenched from dioxane/water (60/40) at 1 wt % polymer.

PREFERENTIAL SEGREGATION

OF CORONA CHAINS:

ARE VESICLES UNDER EQUILIBRIUM CONTROL?ARE VESICLES UNDER EQUILIBRIUM CONTROL?

WORKING HYPOTHESIS ON THERMODYNAMIC CURVATURE STABILIZATION

SHORT CHAINSTO THE INSIDE

LONG CHAINSTO THE OUTSIDE

POLYMER WITH FLUORESCENT LABEL

Bu

COOH

HCH2 CH CH2 CH CH2 CH 295 X PS295-Py-b-PAAxX = 12, 45, 74

Abs

orpt

ion

UV-vis spectrum of pyrene Emission spectrum of vesicles in solution upon irradiation at 343 nm

Wavelength (nm)360 380 400 420 440 460

Inte

nsity

(a.u

.)

Wavelength (nm)

250 300 350 400

Parent system: PS300-b-PAA44

L. Luo and A. Eisenberg, JACS 2001, 123, 1012-1013

Proof of Segregation by Block Length in Vesicles

Modified Stern-Volmer equation: φφ

11

0

0 +=− KQII

I

Spherical micelles

[Tl+]/mM0.0 0.2 0.4 0.6 0.8 1.0

1

2

3

4Vesicles

[Tl+]/mM0.0 0.2 0.4 0.6 0.8 1.0

I 0/I

1

2

3

4

PS295-Py-b-PAA74

PS295-Py-b-PAA45

PS295-Py-b-PAA12

I 0/I

PS295-Py-b-PAA12

PS295-Py-b-PAA45

PS295-Py-b-PAA74

Apparent φ and K values of the PS-b-PAA Micelles and Vesicles

micelles vesicles

system φ K(mM-1) φ K(mM-1)

PS300-b-PAA44/PS295-Py-b-PAA12

0.91±0.07*

(0.85)**

9.5±1.0(9.9)

0.065±0.003(0.065)

9.0±0.6(9.0)


0.92±0.07(0.85)

9.2±0.9(9.7)

0.53±0.02(0.53)

8.9±0.4(8.9)


0.91±0.07(0.85)

9.3±0.9(9.8)

0.88±0.05(0.83)

8.4±0.6(8.8)

*: value± standard error.**: the numbers in brackets were used to calculate the lines in the Figure. They were chosen to give the best fit. All the values are within the error limits.

Laibin Luo & Adi Eisenberg, Langmuir 2001, 17, 6804

Segregation in PS300-b-PAA44 copolymer vesicles

PS30 0-b- PAA44

φ = 0.91

φ = 0.065

PS295-Py-b-PAA12

PS3 0 0-b- PAA4 4 PS3 0 0-b- PAA4 4

φ = 0.91

φ = 0.88

PS295-Py-b-PAA7 4

PS3 0 0-b- PAA4 4

PS295-Py-b-PAA4 5

φ = 0.92

φ = 0.53

Size-dependent segregation of hydrophilic block in PS-b-PAA diblock copolymer vesicles

Vesicle Size (nm)0 200 400 600 800 1000 1200

Que

nchi

ng P

erce

ntag

e

0.0

0.2

0.4

0.6

0.8

1.0PS310-b-PAA28/PS295-Py-b-PAA74




Is Size Dependent Segregation Reversible?

[Tl+]0.0 0.2 0.4 0.6 0.8 1.0

I 0/I

1.00

1.05

1.10

1.15

1.20

1.25

1.30

1.35

1.40PS300-b-PAA44/PS295-Py-b-PAA12

66.7%

50.0%

39.4%

28.6%

24.5%

increasing water contentdecreasing water content

Run

#

1

2

3

4

5

6

7

8

9

Reversibility of chromophore segregation in response to change in vesicle size induced by increasing or decreasing

water contents for PS300-b-PAA44 with 5% PS295-Py-b-PAA12 in 44.4/55.6 THF/Dioxane mixture

Experiment# (direction)

Water content /%

Vesicle size /nmφ (accessibility) /%

Polymer concentration /%Experiment# (direction)

Water content /%

Vesicle size /nm

φ (accessibility) /%Polymer concentration /%

1

24.591±3

4.82±0.06

7.55

228.6

100±49.73±0.09

7.14

339.4

120±513.8±0.2

6.06

450.0

151±619.8±0.2

5.00

566.7

201±325.9±0.3

3.339

24.5

91±24.95±0.04

1.22

8

28.6

99±59.87±0.06

1.43

7

39.4

120±413.9±0.2

1.97

6

50.0

150±620.2±0.2

2.50

Next: different interfaces in and out and inversion possibility

CAN DIFFERENT GROUPS BE ATTACHED INSIDE AND OUTSIDE?

GOAL: PAA insideP(4-VP) outside

POLYMERS USED:

PS300-b-PAA11 (SHORT PAA FOR INSIDE)

PS310-b-P(4-VP)33 (LONG P(4-VP) FOR OUTSIDE)

PS295-Py-b-PAA12 (LABELED SHORT PAA)

PS300-b-PAA44* (FOR ζ COMPARISON)

PREP: DMF, adjust pH to 3, add water to 50%, quench, dialyze* dioxane, add water to 40%, quench, dialyze

BLOCK COPOLYMERS RESULTING MORPHOLOGIES

PS310-b-P(4-VP)33 60% VESICLES; D=88±12nm; Wall=26±2nm

PS300-b-PAA11 35%PS295-Py-b-PAA12 5%

PS300-b-PAA11 LCMs

PS310-b-P(4-VP)33 VESICLES; D=102±14nm; Wall=26±2nm

PS310-b-P(4-VP)33 60% VESICLES; D=90±12nm; Wall=26±2nm

PS300-b-PAA11 40%

PS300-b-PAA44 VESICLES; D=98±7nm; Wall=26±3nm

OUTSIDE OF VESICLES STUDIED BY pH DEPENDENCE OF ζ-POTENTIAL

-60

-40

-20

0

20

40

pH2 3 4 5 7 8 9 106

ζpotential / m

V

EXTERIOR OF MIXED VESICLES SAME AS THAT OF PS310-b-P(4-VP)33 VESICLES

PS300-b-PAA44

PS310-b-P(4-VP)33

PS310-b-P(4-VP)33/PS300-b-PAA11

PAA26-b-PS890-b-P4VP40

O O

Nn

R

Hm x l

NH

F. Liu AND A. Eisenberg, Angewandte Chemie Int. Ed. 2003

.

The charges are on the chains, counterions are not shown

F. Liu and A Eisenberg, JACS 2003

HCl

NaOH

PAA-b-PS-b-P4VP

in DMF/THF

H2O

H2O

PAA-b-PS-b-P4VP

PAA -b-PS-b-P4VP

Vesicles with P4VP outside

Vesicles with PAA outside

PREPARATION OF THE TWO TYPES OF VESICLES

NEXT:INVERSION

Vesicles with PAA Outside

Vesicles with both PAAand P4VP outside

Vesicles withP4VP outside

2 h 6 h

INVERSION OF VESICLES, SCHEMATIC

Critical water content…..

log C0

-6.0 -5.5 -5.0 -4.5 -4.0 -3.5 -3.0 -2.5

CW

C (w

t%)

2.0

2.5

3.0

3.5

4.0

DMF

DMF/THF (85/15, wt/wt)

DMF/THF (85/15 w/w),[HCl]/[4VP]:5.6)

Figure 7. Critical water content vs logarithm of the polymer concentration in various solvents or solvent mixtures

Critical water content…..

log C0

-6.0 -5.5 -5.0 -4.5 -4.0 -3.5 -3.0 -2.5

CW

C (w

t%)

2.0

2.5

3.0

3.5

4.0

DMF

DMF/THF (85/15, wt/wt)

DMF/THF (85/15 w/w),[HCl]/[4VP]:5.6)

Critical water content vs logarithm of the polymer concentration in various solvents or solvent mixtures.

CWC vs POLYMERCONCENTRATION

Extrapolation to 30% water gives a CMC of 10-60

Next: control of wall thickness

Diameter (Wall-thickness)in Dioxane/THF (3/1)

Diameter (Wall-thickness)in Dioxane

292±118 (42±5)340±149 (42±3)

424±149 (38±4)

301±118 (33±4)

116±19 (28±2)

94±16 (24±2)

96±17 (27±3)

Micelles (20±2)

269±111 (39±4)177±85 (22±2)

9.77PAA47-b-PS434

104±22 (20±2)

202±106 (36±4)11.32PAA47-b-PS368

147±76 (34±3)11.66PAA47-b-PS356

108±23 (28±3)13.27PAA47-b-PS307

100±19 (27±3)14.59PAA47-b-PS275

75±9 (23±2)15.93PAA47-b-PS248

Micelles (20±2)19.26PAA47-b-PS197

370±127 (39±4)9.49PAA34-b-PS324

134±60 (22±3)12.45PAA34-b-PS239

86±14 (19±4)15.31PAA34-b-PS188

% PAA Block

Sizes and Wall-thicknesses of Vesicles Prepared from VariousPAA-b-PS block Lengths in Two Solvent Systems

y = 0.1014x - 1.9141R2 = 0.9876

20

25

30

35

40

45

50

240 290 340 390 440

DP of Styrene block

Wal

l-thi

ckne

ss (n

m)

Relation between the poly(styrene) block length and the wall-thicknessin vesicles made from the PAA47-b-PSn block copolymers series

Relation between the square root of the poly(styrene) block length and the wall-thickness in vesicles made from the

PAA47-b-PSn block copolymers series

Wall-thickness (nm)

y = 0.2665x + 9.6846R2 = 0.9851

15

16

17

18

19

20

21

20 25 30 35 40 45

(DP

of S

tyre

ne b

lock

)1/2

(nm

)1/2

y = 0.2665x + 9.6846R2 = 0.9851

y = 9.7445x + 22.758R2 = 0.9876

200

250

300

350

400

450

20 25 30 35 40 4515

16

17

18

19

20

21

22

23

24

25

Relationship between Average Vesicles wallRelationship between Average Vesicles wall--thickness (d) and the thickness (d) and the Degree of Polymerization of Styrene block (Degree of Polymerization of Styrene block (DPDPStyreneStyrene) or (DP) or (DPStyreneStyrene))1/21/2

for PAAfor PAA4747--bb--PSPSnn

Average Wall-thickness (d±σ, nm)

DP

of S

tyre

ne B

lock

Bloc

kSt

yren

eof

DP

Next: Size control

y = 0.0045x2 - 1.8875x + 272.17R2 = 0.9728

50

100

150

200

250

300

350

400

450

500

230 280 330 380 430

DP Styrene

Ves

icle

Dia

met

er (n

m)

Average Vesicle Diameter of PAA47-b-PSn Block Copolymers as a Function of DPStyrene

0

20

40

60

80

100

120

140

160

50 100 150 200 250 300 350 400 450

♦ PAA47-b-PSn in Dioxane

▲ PAA47-b-PSn in Dioxane/THF (3/1)

● PAA34-b-PSn in Dioxane

■ PAA34-b-PSn in Dioxane/THF (3/1)

Average Vesicles Diameter (D, nm)

Size

Sta

ndar

d D

evia

tion

(σ)

PolydispersityPolydispersity vs. Vesicle Sizesvs. Vesicle Sizes

The size change of PS300-b-PAA44 diblock copolymer vesicles with changing water content and organic solvent

composition

THF (%)0 10 20 30 40 50 60 70

Wat

er (%

)

0

10

20

30

40

50

60

70

80

Rods + Vesicles

119 119 100

100121

120

149

150151

120

201 150 119

91

102

100

100100 100

90

919191

8988

Reversibility of vesicle sizes in response toincreasing or decreasing water contents for PS300-b-PAA44 vesicles in

THF/Dioxane (44.4/55.6) solvent mixture

H2O

20.0 24.5 (91) 28.6 (100) 50.0 (151)

H2O

H2O H2O

H2O

66.7 (201)

200 nmWater content / % (size / nm)

39.4 (119)T

HF/

DIO

X

TH

F/D

IOX

TH

F/D

IOX

TH

F/D

IOX

TH

F/D

IOX

20.0 24.5 (91) 39.4 (119) 50.0 (151)28.6 (99)

Laibin Luo & Adi Eisenberg, Langmuir 2001, 17, 6804; 2002, 18, 1952.

Diameter (nm)

80 150 200 300 400 600 800 1500100 1000

Num

ber

of v

esic

les

0

2

4

6

8

10

12

14

SIZE DISTRIBUTIONS OF PS310-b-PAA28 VESICLES(FROM TEM)

D = 90±3nm; σ/D = 0.03Prepared in DMF/THF (79.6/20.4 w/w)

D = 1010±340nm; σ/D = 0.34Prepared in DMF/THF (38.8/61.2 w/w)

TOTAL INTERFACIAL AREA VS. VESICLE SIZE

d

2R(=D)

( )( )[ ]

( )

( )[ ]

( )[ ]

( )[ ]( )[ ]

( )[ ]( )[ ]

322

22

3

22

22

33

33

33

33

22

2

2

33223

3

π4*π

34

π34

π34

π34π

34

)π4π4

π4

dRddRdRdRV

dRdRRV

dRRdRR

V

dRR

V

dRR

dRR

dRRdR

R

+−++

=

−−−+

=

−+−−

=

−−=

−−=

−−=

−+=

−=

=

Wall Total

3Wall Total

wallTotal

wallTotal

R

Area SurfaceTotal

Vesicles of Number

Wall of Volume

SurfaceTotal SurfaceInside

SurfaceOutside

1. For Radius (R) >> Wall thickness (d),

2. For R ∼ d,

Assume

WHY DO VESICLE SIZES INCREASE WITH INCREASING WATER CONTENT?

dVA TOTALWALL2

=

322

22

33223

dRddRdRdRVA TOTALWALL+−++

=

),1(10 336 cmmVTOTALWALL == −

Total Surface Area vs. Vesicle Size

nmd 27=

d

2R(=D)

Vesicle Radius (/nm)

50 70 200 300 500 700100 1000

Surf

ace

Are

a (/m

2 )

100

200

300

σ/D

0

5

10

15

20

25

30

35

40

II- Effect of HCl

Polymer + acid

Water content (% w/w)0 10 20 30 40

Tur

bidi

ty

0

1

2

3

HCl = 63.8 uM HCl = 640.9 uM HC =1272.1 uM

HCl = 0

Polymer only

In the presence of acid we observe:

no shift in CWC (ca. 10.5% w/w)

after vesicle formation(ca. 11.5 % w/w) turbidity ↑i.e. bigger vesicles form

0.5% solutions of PS310-b-PAA36 in dioxane

In the absence of additives, poly(acrylic acid) is slightly ionizedThe electrostatic repulsion between chains

is reduced by adding

Salt, shields the charges

Acid,protonates the

carboxyl groupsWhen repulsion among chains

decreases Aggregation number increases

Larger vesicles form

or

Why does NaCl or HCl cause larger vesicles to form?

50

150

250

350

450

10 20 30 40Water Content (% w/w)

Avg

. Ves

icle

Dia

met

er (n

m)

Effect of additives on vesicle size

HCl = 64 μM

polymer only

NaOH =16 μM

NaCl = 2.7 mM

PS310-b-PAA36

III- Effect of NaOH

Water content (% w/w)

0 10 20 30 40

Tur

bidi

ty

0

1

2

3

NaOH = 0NaOH = 16.4 uMNaOH = 33.4 uMNaOH = 66.6 uMNaOH = 333.5 uM

Polymer + NaOH

Polymer onlyIn the presence of base we observe that:

for NaOH > 16.4 uM, no self-assembly

for NaOH = 16.4 uM, CWC shifts(10.5 → 12.5 % water)

after vesicle formation, - turbidity ↓i.e. smaller vesicles form- turbidity increases ONLY slightly with water content

0.5% solutions of PS310-b-PAA36 in dioxane

Why does NaOH cause smaller vesicles to form?

NaOH deprotonates poly(acrylic acid)

Electrostatic repulsion among chains ↑

For NaOH >16.4 uM,

the high ion contentdecreases solubility

For NaOH = 16.4 uM,chain repulsion is high aggregation number ↓smaller vesicles form

Next: fission and fusion mechanisms and fusion kinetics

MECHANISM OF VESICLE FUSION

COALESCENCE AND FORMATION OF CENTER WALL

DESTABILIZATION OF CENTER WALL

ASYMMETRIC DETACHMENTOF CENTER WALL

RETRACTION OF CENTERWALL INTO OUTER WALL

FORMATION OF UNIFORM OUTER WALL

CONTACT AND ADHESION

MECHANISM OF VESICLE FISSION

ELONGATION

INTERNAL WAIST FORMATION

NARROWING OFEXTERNAL WAIST

SPHERICAL VESICLE

COMPLETE SEPARATION

• System: 1.0 wt % PS310-b-PAA52 in dioxane/water (11.5%)

2.0 mM 5.1 mM 11.0 mM9.2 mM 17.1 mM

[SDS] increases

Susan E. Burke and Adi Eisenberg Langmuir 2001, 17, 8341.

Effect of SDS on Morphology

• System: 1.0 wt % PS310-b-PAA52 in dioxane/water in the presence of SDS

rods

rods and vesicles

vesicles

spheres + rods

spheres


MORPHOLOGICAL PHASE DIAGRAM

Effect of SDS on Morphological Transitions

• System: 1.0 wt % PS310-b-PAA52 in dioxane/water


15 to 16 wt.% H2O for PS310-b-PAA36 in Dioxane

0.95

0.97

0.99

1.01

1.03

1.05

60 70 80 90 100 110 120 130 140Time (sec.)

Turb

idity

R2 = 0.98

y = yo + A(1-e-tb)

A = 0.061 +/- 0.001yo = 0.969 +/- 0.001

b = 0.066 +/- 0.002

22 to 23 wt.% H2O for PS310-b-PAA36 in Dioxane

1.29

1.30

1.31

1.32

1.33

1.34

1.35

1.36

1.37

60 80 100 120 140 160 180

Time (sec.)

Turb

idity

Experimental Smoothed Calculated

y = yo + A(1-e-tb)

R2 = 0.93

A = 0.044 +/- 0.001yo = 1.296 +/- 0.001

b = 0.040 +/- 0.003

TWO EXAMPLES OF KINETIC RUNS OF VESICLE SIZE CHANGES

An example of change in turbidity as a function of time upon 5wt% water jumps

0.5 wt.% PS310-b-PAA36 in Dioxane

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0 25 50 75 100 125 150Time (sec.)

Turb

idity

17.5 wt.% 22.5 wt.% 27.5 wt.% 32.5 wt.%

T = A (1-e-bt)

Effect of the magnitude of the water jump

0.5wt.% of PS310-PAA36 in Dioxane R2 = 0.90

R2 = 0.9171

R2 = 0.9084

0102030405060708090

15 20 25 30 35Water Content (wt.%)

Avg

.Rel

axat

ion

time

(sec

.)

1w t % jumps 2w t% jumps5w t% jumps 7w t% jumpsLi (1 % j ) Li (2 % j )

PS300-b-PAA11

PS310-b-PAA28 PS300-b-PAA75

Terreau, O.; Luo, L.; Eisenberg, A. Langmuir 2003, 19, 5601-5607

Length Segregation of Corona Chains Decreases Vesicle Sizes

0

100200

300400

500600

700

1 1.5 2 2.5PAA Chain Polydispersity

Aver

age

Vesi

cle

Dia

met

er

(nm

)

Dynamic Light ScatteringTansmission Electron Microscopy

Terreau, O.; Luo, L.; Eisenberg, A. Langmuir 2003, 19, 5601-5607

Effect of Corona Block Polydispersity on Sizes of Vesicles Made from Polystyrene-b-Poly(acrylic acid)

Solvent content, number average molecular weight, and polymer concentration were kept constant.

n

Next: filling and release

What’s DXR• DXR.HCl: doxorubicin hydrochloride

• Anti-cancer drug• Molecular weight = 580 (g/mol) • Water soluble (50 mg/ml)

Active Loading into Vesicles

pH = 6.3

pH = 2.5

Use vesicles as model carriers for DoxorubicinInduce loading by creating a transmembrane pH gradient

vs.

ΔpH ≈ 4 ΔpH = 0

pH = 2.5

pH = 2.5pH = 6.3

pH = 2.5

“Active” vs. “Passive” Loading

As a function of the wall permeability (addition of dioxane as a plasticizer)

Solvent content in the PS200-rich phase as a function of the water content (dotted lines extrapolate the cwc). The insert shows the plot against the water increment beyond the cwc.

pH = 2.5

pH = 2.5

Active vs. Passive Loading

Vesicles prepared from PS310-b-PAA36

Common solvent: dioxane

Loading Efficiency

0

20

40

60

80

100

120

0 20 40 60 80Dioxane content (% w/w)

% m

oles

load

pH = 2.5

pH = 6.3

Loading Mechanism

= XNH2

= XNH+3

+: neutral form is permeable

: protonated form is NOT permeable

pH = 6.3pH = 2.5

+

Release of DOX from PS310-b-PAA36 vesicles

Lim Soo, P.; Choucair, A.; Eisenberg, A.; In Press

Time (seconds)1/2

0 200 400 600 800 1000 1200 1400 1600

Q (m

oles

/ cm

2 )/ 1

x 10

-9)

0

2

4

6

8

100% dioxane/ 100% water25% dioxane/ 75% water50% dioxane/ 50% water

360 380 400 420 440 460 480 5000

1

2

3

4

5

63.00

4.00 4.60

7.40

6.00

7.00

8.00

9.0010.00

W avelength (nm )

Inte

nsity

(CPS

) X 1

0-6

5 .00

A

Excitation spectra of 8-hydroxypyrene-1,3,6-trisulphonate (HPTS)

3 4 5 6 7 8 9 10

0

100

200

300

pH

I 403

/I 454

0

1

2

3

4I454 /I403

B

Calibration profiles of HPTScurves were taken as I454/I403 or I403/I454 vs. pH.

400 420 440 460 480

Wavelength (nm)

0 h 1 h

144 h

7%

B

76 h

365 h

1056 h

400 420 440 460 480

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

Inte

nsity

(a.u

.)

Wavelength (nm)

0%

A400 420 440 460 480

Wavelength (nm)

0 h

1 h

20 h43 & 70 h

28%

D400 420 440 460 480

Wavelength (nm)

0 h

1/4 h 3, 6, 23 h

E

40%

400 420 440 460 480

Wavelength (nm)

0 h

1 h

3 h

5 h

19 h

46 h92 h

140 h 265, 338 h

14%

C

Time evolution of fluorescence excitation spectra from vesicle solutions with added HPTS

at different dioxane contents;

A: 0 wt%; B: 7 wt%; C: 14 wt%; D: 28 wt%; E: 40 wt%;

0 5 10 15 20

0

2

4

6

8

[H+ ]x

107

t1/2

0 3 6 9 12 15 180.0

0.3

0.6

0.9

1.2

[H+ ] x

107

t1/2

0%

7%

14%

28%

40% 7%

Plots of proton concentration [H+] against the square root of diffusion time t.

5 10 15 20 25 30 35 40 45

0

1

2

3

4lo

g[D

*(Φ)/

D*(

7%)]

dioxane content in solution (%)

Plot of log[D*(Φ)/D*(7%)] against dioxane content.

Vesicles – Summary (1)

Many types of vesicles can be prepared (equilibrium)

Sizes can be thermodynamically and reversibly controlled by

Water content, ion content, solvent composition, molecular weight distribution of corona block, relative block length, polydispersity, etc

Part of a morphological continuum spheres rods vesicles

Kinetics and mechanisms of transitions are known

Vesicle curvature stabilized by chain segregation: Longer chains outside, shorter chains inside.

Segregation is size dependent and reversible.

Vesicles – Summary (2)Interface compositions can be controlled by using diblock

mixtures,

for example: PS-b-PAA with PS-b-PVP.

Vesicles with opposite interfaces from ABC triblocks

(PAA-b-PS-b-PVP)

Triggered inversion is possible.

Wall thickness is controllable

(Small molecules inside vesicles)

(Active loading is possible. Release occurs by diffusion)

(Wall permeability can be controlled (by 100x))

F. LIUN. DUXIN

“PARTING IS SUCH SWEET SORROW”

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