BLOCK COPOLYMER VESICLES

Transcription

1 BLOCK COPOLYMER VESICLES UNIVERSITY OF BAYREUTH TUESDAY, JUNE 3, 006 ADI EISENBERG

2 NICE TO SEE YOU AGAIN

3 OUTLINE INTRODUCTION (BRIEF REVIEW OF FIRST LECTURE) SMALL MOLECULE AMPHIPHILES AND DIBLOCK COPOLYMERS METHODS OF PREPARATION ACCESSIBLE MORPHOLOGIES THERMO, KINETICS AND MORPHOLOGICAL CONTROL MECHANISMS VESICLES, PREPARATION AND THERMODYNAMICS TYPES OF VESICLES THERMODYNAMIC CURVATURE STABILIZATION CONTROL OF INTERFACIAL COMPOSITION INVERSION EQUILIBRIUM CONTROL OF SIZES TRIGGERS FOR MORPHOLOGICAL AND DIMENSIONAL CHANGES (IONS, SURFACTANTANTS, WATER ) KINETICS AND MECHANISMS OF SIZE CHANGES VESICLES, FILLING AND NON-DESTRUCTIVE RELEASE FILLING OF ACTIVE INGREDIENTS (DOX) DIFFUSIONAL RELEASE OF CONTENTS (DOX) DIFFUSION OF PROTONS THROUGH VESICLE WALLS CONCLUSIONS

4 BLOCK AND GRAFT COPOLYMERS AB Dibloc ABA BAB Tribloc Alternating bloc Tapered bloc Graft

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

6 Morphologies of Bloc Copolymers in Aqueous Solutions Star Micelle Crew-cut Micelle (PS 3 -b-pana 400 ) (PS 40 -b-pana 46 ) :00 0:

7 Morphologies of Bloc Copolymers in Aqueous Solutions (Continued) 0 Vesicle Lamella

8 NEXT: PREP. AND MORPH.

9 PREPARATIVE METHODS () TEMPERATURE QUENCH AND FREEZE-DRY EQUILIBRATED SOLUTIONS Add water to polymer solution in dioxane At predetermined water concentration, drop temperature to near - liquid N Warm under vacuum to sublime off dioxane and water. WATER QUENCH EQUILIBRATED SOLUTION AND DIALYZE Add water to polymer solution At predetermined water concentration, quench into water Dialyze

10 Spherical micelles Rods Bicontinuous Rods Lamellae PS(00)-b-PAA() PS(90)-b-PAA(0) PS(90)-b-PAA(0) PS(3)-b-PAA(0) Lamellae Vesicles HHH LCM PS(49)-b-PAA(0) PS(40)-b-PAA(3) PS(40)-b-PAA(3) PS(00)-b-PAA(4) Cameron, N. S.; Corbierre, M. K.; Eisenberg, A. Can. J. Chem. 999, 77, 3.

11 THERMODYNAMICS OF FORMATION OF CREW-CUT AGGREGATES MORPHOGENIC CONTRIBUTIONS TO ΔG. CHAIN STRETCHING IN CORE. REPULSION AMONG CORONA CHAINS 3. INTERFACIAL ENERGY FOR EXAMPLE: AS WATER IS ADDED. INTERFACIAL ENERGY INCREASES. TOTAL INTERFACIAL AREA DECREASES 3. CORE RADIUS INCREASES 4. NUMBER OF MICELLES DECREASES 5. CORE CHAINS ARE STRETCHED 6. DISTANCE BETWEEN CORONA CHAINS DECREASES 7. CORONA CHAIN REPULSION INCREASES 8. MORPHOLOGY CHANGES AT SOME CRITICAL POINTS LOW WATER CONTENT HIGH WATER CONTENT

12 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

13 Phase Diagram of Fractionated PS 30 -b-paa 5 in Dioxane/H O S + R Copolymer Concentration (wt%) 0 0. S R R + V V Dioxane (wt%) Water Content (wt%) Water Content (wt%) Copolymer (wt%) Hongwei Shen & Adi Eisenberg, J. Phys. Chem. B 999, 03, 9473

14 Now: Vesicles

15 TYPES OF VESICLES 00 nm 500 nm small uniform vesicleslarge polydisperse entrapped vesicles PS 40 -b-paa 3 vesicles PS 00 -b-peo 30 PS 00 -b-paa nm 00 nm hollow concentric vesicles PS 3 -b-paa 0 onion PS 60 s-b-p4vpdeci 70 tube-walled PSvesicles 00 -b-peo 30 Original references given in S. Bure and A. Eisenberg Macromolecular Symposia (Warsaw IUPAC meeting)

16 THEMODYNAMICALLY STABLE VESICLES ARE PRODUCED BY WORKING IN LARGE REGION OF THE PHASE DIAGRAM WHERE VESICLES ARE THE ONLY (OR THE DOMINANT)MORPHOLOGY SIZES, WALL THICKNESS AND INTERFACE COMPOSITION CAN BE CONTROLLED BY FINE TUNING THE DETAILED PREPARATIVE CONDITIONS (WATER CONTENT, SOLVENT COMPOSITION, ph, IONIC STRENGTH, ETC.)

17 QUESTIONS ABOUT VESICLES () 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?

18 QUESTIONS ABOUT VESICLES () 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?

19 Changes in Aggregate Morphology Are Associated With Changes in Turbidity.0 PS 30 -b-paa 5 % w/w in dioxane.5 Rods to Vesicles Turbidity.0 Water Addition 0.5 Spheres to rods 0.0 Micellization Dioxane Addition Water Content (wt%) Shen, H.; Eisenberg, A. J. Phys. Chem. B. 999, 03,

20 Turbidity Increase With Time After % Water Jump PS 30 -b-paa 5 % w/w in dioxane wt%. Turbidity wt% Time (sec) Chen, L.; Shen, H.; Eisenberg, A. J. Phys. Chem. B. 999, 03,

21 0 sec Chen, L.; Shen, H.; Eisenberg, A. J. Phys. Chem. B. 999, 03,

22 .5.4 Fitting Quality Experimental Curve 0 Turbidity A B C Single Exponential Fit y = y 0 + a( exp( *t)) Double Exponential Fit D y = y 0 + a( exp( *t)) + b( exp( *t)) ((T cal. - T exp. )/T exp. ) (%) Time (sec) Chen, L.; Shen, H.; Eisenberg, A. J. Phys. Chem. B. 999, 03,

23 Concentration of Each Species + + = + + = = ) exp( ) ( ) exp( ) ( ) exp( ) ( ) ( ) exp( ) ( ) ( ) exp( ) ( ) exp( ) ( m m m t m m m m t m m m C C m m m t m m m m m t m m m m C C m m m t m m m m m m m t m m m m m m C C f f f f f f r vt b b b f b f r lt b b f b b f b b r rt m and m stand for: [ ] [ ] ) 4( ) ( ) ( ) 4( ) ( ) ( f f b f b b b f b f b f b f f f b f b b b f b f b f b f m m = =

24 Concentration of Each Species.5 Vesicle.0 C/C r0 0.5 Lamella Rod Time (sec) Chen, L.; Shen, H.; Eisenberg, A. J. Phys. Chem. B. 999, 03,

25

26 Next: Curvature stabilization mechanism

27 Transmission electron micrograph (TEM) of vesicles of PS 300 -b-paa 44 Quenched from dioxane/water (60/40) at wt % polymer.

28 ARE VESICLES UNDER EQUILIBRIUM CONTROL? ARE VESICLES UNDER EQUILIBRIUM CONTROL? WORKING HYPOTHESIS ON THERMODYNAMIC CURVATURE STABILIZATION PREFERENTIAL SEGREGATION OF CORONA CHAINS: SHORT CHAINS TO THE INSIDE LONG CHAINS TO THE OUTSIDE

29 POLYMER WITH FLUORESCENT LABEL Bu Parent system: PS 300 -b-paa 44 CH CH CH CH CH CH H PS 95 X 95 -Py-b- COOH PAA x X =, 45, 74 Absorption Intensity (a.u.) Wavelength (nm) Wavelength (nm) UV-vis spectrum of pyrene Emission spectrum of vesicles in solution upon irradiation at 343 nm L. Luo and A. Eisenberg, JACS 00, 3, 0-03

30 Proof of Segregation by Bloc Length in Vesicles 4 Spherical micelles Vesicles 4 I 0 /I 3 PS 95 -Py-b-PAA 74 PS 95 -Py-b-PAA 45 PS 95 -Py-b-PAA [Tl+]/mM PS 95 -Py-b-PAA 74 PS 95 -Py-b-PAA 45 PS95-Py-b-PAA [Tl ]/mm 3 I 0 /I Modified Stern-Volmer equation: I I I 0 φkq 0 = + φ

31 Apparent φ and K values of the PS-b-PAA Micelles and Vesicles micelles vesicles system φ K(mM - ) φ K(mM - ) PS 300 -b-paa 44 / 0.9±0.07 * 9.5±.0 PS 95 -Py-b-PAA (0.85) ** (9.9) 0.065±0.003 (0.065) 9.0±0.6 (9.0) PS 300 -b-paa 44 / PS 95 -Py-b-PAA ±0.07 (0.85) 9.±0.9 (9.7) 0.53±0.0 (0.53) 8.9±0.4 (8.9) PS 300 -b-paa 44 / PS 95 -Py-b-PAA ±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 bracets 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 00, 7, 6804

32 Segregation in PS 300 -b-paa 44 copolymer vesicles PS 300 -b-paa 44 PS 300 -b-paa 44 PS 300 -b-paa 44 PS 300 -b-paa 44 PS 95 -Py-b-PAA PS 95 -Py-b-PAA 45 PS 95 -Py-b-PAA 74 φ = 0.9 φ = 0.9 φ = 0.9 φ = φ = 0.53 φ = 0.88

33 Size-dependent segregation of hydrophilic bloc in PS-b-PAA dibloc copolymer vesicles.0 Quenching Percentage PS 30 -b-paa 8 /PS 95 -Py-b-PAA 74 PS 300 -b-paa 44 /PS 95 -Py-b-PAA 74 PS 30 -b-paa 8 /PS 95 -Py-b-PAA 0.0 PS 300 -b-paa 44 /PS 95 -Py-b-PAA Vesicle Size (nm)

34 Is Size Dependent Segregation Reversible?.40 PS300 -b-paa 44 /PS 95 -Py-b-PAA increasing water content decreasing water content 66.7% Run# 5 I 0 /I % %.0 8.6% % [Tl + ]

35 Reversibility of chromophore segregation in response to change in vesicle size induced by increasing or decreasing water contents for PS 300 -b-paa 44 with 5% PS 95 -Py-b- PAA in 44.4/55.6 THF/Dioxane mixture Experiment# (direction) Water content /% Vesicle size /nm 9±3 00±4 0±5 5±6 0±3 φ (accessibility) /% 4.8± ± ±0. 9.8±0. 5.9±0.3 Polymer concentration /% Experiment# (direction) Water content /% Vesicle size /nm 9± 99±5 0±4 50±6 φ (accessibility) /% 4.95± ± ±0. 0.±0. Polymer concentration /%

36 Next: different interfaces in and out and inversion possibility

37 CAN DIFFERENT GROUPS BE ATTACHED INSIDE AND OUTSIDE? GOAL: PAA inside P(4-VP) outside POLYMERS USED: PS 300 -b-paa PS 30 -b-p(4-vp) 33 PS 95 -Py-b-PAA PS 300 -b-paa * 44 (SHORT PAA FOR INSIDE) (LONG P(4-VP) FOR OUTSIDE) (LABELED SHORT PAA) (FOR ζ COMPARISON) PREP: DMF, adjust ph to 3, add water to 50%, quench, dialyze * dioxane, add water to 40%, quench, dialyze

38 BLOCK COPOLYMERS PS 300 -b-paa RESULTING MORPHOLOGIES LCMs PS 30 -b-p(4-vp) 33 VESICLES; D=0±4nm; Wall=6±nm PS 30 -b-p(4-vp) 33 60% VESICLES; D=90±nm; Wall=6±nm PS 300 -b-paa 40% PS 30 -b-p(4-vp) 33 60% VESICLES; D=88±nm; Wall=6±nm PS 300 -b-paa 35% PS 95 -Py-b-PAA 5% PS 300 -b-paa 44 VESICLES; D=98±7nm; Wall=6±3nm

39 ζ potential / mv OUTSIDE OF VESICLES STUDIED BY ph DEPENDENCE OF ζ-potential PS 30 -b-p(4-vp) 33 /PS 300 -b-paa PS 30 -b-p(4-vp) 33 PS 300 -b-paa ph EXTERIOR OF MIXED VESICLES SAME AS THAT OF PS 30 -b-p(4-vp) 33 VESICLES

40 PAA 6 -b-ps 890 -b-p4vp 40 n N m x l H O OH R N F. Liu AND A. Eisenberg, Angewandte Chemie Int. Ed. 003

41 PREPARATION OF THE TWO TYPES OF VESICLES PAA-b-PS-b-P4VP H O HCl Vesicles with P4VP outside PAA-b-PS-b-P4VP in DMF/THF NaOH H O PAA -b-ps-b-p4vp. Vesicles with PAA outside The charges are on the chains, counterions are not shown F. Liu and A Eisenberg, JACS 003

42 NEXT: INVERSION

43 INVERSION OF VESICLES, SCHEMATIC h 6 h Vesicles with PAA Outside Vesicles with both PAA and P4VP outside Vesicles with P4VP outside

44 CWC vs POLYMERCONCENTRATION Critical water content CWC (wt%) CWC (wt%) DMF DMF/THF DMF/THF (85/5 (85/5 w/w),[hcl]/[4vp]:5.6) w/w),[hcl]/[4vp]:5.6) DMF/THF (85/5, wt/wt) log C 0 Critical water content vs logarithm of the polymer concentration in various solvents or solvent mixtures. Figure 7. Critical water content vs logarithm of the polymer concentration in various solvents or solvent mixtures Extrapolation to 30% water gives a CMC of 0-60

45 Next: control of wall thicness

46 Sizes and Wall-thicnesses of Vesicles Prepared from Various PAA-b-PS bloc Lengths in Two Solvent Systems Bloc % PAA Diameter (Wall-thicness) Diameter (Wall-thicness) in Dioxane in Dioxane/THF (3/) PAA 47 -b-ps ±49 (4±3) 9±8 (4±5) PAA 47 -b-ps ±49 (38±4) 0±06 (36±4) PAA 47 -b-ps 356 PAA 47 -b-ps 307 PAA 47 -b-ps 75 PAA 47 -b-ps ±8 (33±4) 6±9 (8±) 94±6 (4±) 96±7 (7±3) 47±76 (34±3) 08±3 (8±3) 00±9 (7±3) 75±9 (3±) Micelles (0±) PAA 47 -b-ps Micelles (0±) PAA 34 -b-ps ± (39±4) 370±7 (39±4) PAA 34 -b-ps ±85 (±) 34±60 (±3) 86±4 (9±4) PAA 34 -b-ps ± (0±)

47 Relation between the poly(styrene) bloc length and the wall-thicness in vesicles made from the PAA 47 -b-ps n bloc copolymers series 50 Wall-thicness (nm) y = 0.04x -.94 R = DP of Styrene bloc

48 Relation between the square root of the poly(styrene) bloc length and the wall-thicness in vesicles made from the PAA 47 -b-ps n bloc copolymers series (DP of Styrene bloc) / (nm) / y = 0.665x R = Wall-thicness (nm)

49 Relationship between Average Vesicles wall-thicness (d) and the Degree of Polymerization of Styrene bloc (DP( Styrene ) or (DP Styrene for PAA 47 -b-ps n Styrene ) / DP of Styrene Bloc y = 0.665x R = y = x R = Styrene Bloc DP of Average Wall-thicness (d±σ, nm)

50 Next: Size control

51 Average Vesicle Diameter of PAA 47 -b-ps n Bloc Copolymers as a Function of DP Styrene Vesicle Diameter (nm) y = x x R = DP Styrene

52 Polydispersity vs. Vesicle Sizes Size Standard Deviation (σ) PAA 47 -b-ps n in Dioxane PAA 47 -b-ps n in Dioxane/THF (3/) PAA 34 -b-ps n in Dioxane PAA 34 -b-ps n in Dioxane/THF (3/) Average Vesicles Diameter (D, nm)

53 The size change of PS 300 -b-paa 44 dibloc copolymer vesicles with changing water content and organic solvent composition 80 Water (%) Rods + Vesicles THF (%)

54 Reversibility of vesicle sizes in response to increasing or decreasing water contents for PS 300 -b-paa 44 vesicles in THF/Dioxane (44.4/55.6) solvent mixture 00 nm Water content / % (size / nm) (9) 8.6 (00) 39.4 (9) 50.0 (5) 66.7 (0) THF/DIOX THF/DIOX THF/DIOX THF/DIOX THF/DIOX H O H O H O H O H O (9) 8.6 (99) 39.4 (9) 50.0 (5) Laibin Luo & Adi Eisenberg, Langmuir 00, 7, 6804; 00, 8, 95.

55 SIZE DISTRIBUTIONS OF PS 30 -b-paa 8 VESICLES (FROM TEM) 4 D = 90±3nm; σ/d = 0.03 Prepared in DMF/THF (79.6/0.4 w/w) Number of vesicles D = 00±340nm; σ/d = 0.34 Prepared in DMF/THF (38.8/6. w/w) Diameter (nm)

56 Outside Surface Inside Surface = Total Surface Volume of Wall TOTAL INTERFACIAL AREA VS. VESICLE SIZE = = = = Number of Vesicles Total Surface Area 4π ( R d ) [ ( R + R d) )] 4π 4πR = = = = πr π 3 ( R d ) 3 3 [ R ( R d ) ] V 3V π π Total 4 3 V π 3 3 [ R ( R d ) ] V 3 3 [ R ( R d ) ] [ R + ( R d ) ] Wall 3 3 R ( R d ) [ ] Total Wall Total wall Total wall R 3R d + 3 Rd 3Rd * 4π + d + d [ R + ( R d ) ] 3 R(=D) d

57 WHY DO VESICLE SIZES INCREASE WITH INCREASING WATER CONTENT?. For Radius (R) >> Wall thicness (d), A =. For R d, A = 3V Surface Area (/m ) Total Surface Area vs. Vesicle Size TOTALWALL R + Rd + d 3R d 3Rd + d 6 3 Assume VTOTALWALL = 0 m ( = cm 3 ), Vesicle Radius (/nm) 3 V d = 7nm TOTALWALL d σ/d R(=D) d

58 II- Effect of HCl In the presence of acid we observe: 3 Polymer + acid no shift in CWC (ca. 0.5% w/w) Turbidity Polymer only after vesicle formation (ca..5 % w/w) turbidity i.e. bigger vesicles form Water content (% w/w) HCl = 0 HCl = 63.8 um HCl = um HC =7. um 0.5% solutions of PS 30 -b-paa 36 in dioxane

59 Why does NaCl or HCl cause larger vesicles to form? In the absence of additives, poly(acrylic acid) is slightly ionized The electrostatic repulsion between chains is reduced by adding or Acid, Salt, shields the charges protonates the carboxyl groups When repulsion among chains decreases Aggregation number increases Larger vesicles form

60 Effect of additives on vesicle size 450 Avg. Vesicle Diameter (nm) HCl = 64 μm NaCl =.7 mm polymer only 50 NaOH =6 μm Water Content (% w/w) PS 30 -b-paa 36

61 III- Effect of NaOH In the presence of base we observe that: for NaOH > 6.4 um, no self-assembly for NaOH = 6.4 um, CWC shifts (0.5.5 % water) Turbidity 3 0 Polymer only Water content (% w/w) NaOH = 0 NaOH = 6.4 um NaOH = 33.4 um NaOH = 66.6 um NaOH = um Polymer + NaOH after vesicle formation, -turbidity 0.5% solutions of PS 30 -b-paa 36 in dioxane i.e. smaller vesicles form - turbidity increases ONLY slightly with water content

62 Why does NaOH cause smaller vesicles to form? NaOH deprotonates poly(acrylic acid) Electrostatic repulsion among chains For NaOH >6.4 um, the high ion content decreases solubility For NaOH = 6.4 um, chain repulsion is high aggregation number smaller vesicles form

63 Next: fission and fusion mechanisms and fusion inetics

64 MECHANISM OF VESICLE FUSION MECHANISM OF VESICLE FISSION CONTACT AND ADHESION SPHERICAL VESICLE COALESCENCE AND FORMATION OF CENTER WALL ELONGATION DESTABILIZATION OF CENTER WALL ASYMMETRIC DETACHMENT OF CENTER WALL RETRACTION OF CENTER WALL INTO OUTER WALL FORMATION OF UNIFORM OUTER WALL INTERNAL WAIST FORMATION NARROWING OF EXTERNAL WAIST COMPLETE SEPARATION

65 Effect of SDS on Morphology System:.0 wt % PS 30 -b-paa 5 in dioxane/water (.5%).0 mm 5. mm 9. mm.0 mm 7. mm [SDS] increases Susan E. Bure and Adi Eisenberg Langmuir 00, 7, 834.

66 MORPHOLOGICAL PHASE DIAGRAM System:.0 wt % PS 30 -b-paa 5 in dioxane/water in the presence of SDS vesicles rods and vesicles spheres + rods rods spheres Susan E. Bure and Adi Eisenberg Langmuir 00, 7, 834.

67 Effect of SDS on Morphological Transitions System:.0 wt % PS 30 -b-paa 5 in dioxane/water Susan E. Bure and Adi Eisenberg Langmuir 00, 7, 834.

68 TWO EXAMPLES OF KINETIC RUNS OF VESICLE SIZE CHANGES.05 5 to 6 wt.% HO for PS30-b-PAA36 in Dioxane.03 R = 0.98 Turbidity y = y o + A(-e -tb ) Time (sec.) y o = / A = / b = / to 3 wt.% H O for PS 30 -b-paa 36 in Dioxane R = Turbidity Time (sec.) y = y o + A(-e -tb ) y o =.96 +/ A = / b = / Experimental Smoothed Calculated

69 An example of change in turbidity as a function of time upon 5wt% water jumps wt.% PS30-b-PAA36 in Dioxane Turbidity T = A (-e -bt ) Time (sec.) 7.5 wt.%.5 wt.% 7.5 wt.% 3.5 wt.%

70 Effect of the magnitude of the water jump Avg.Relaxation time (sec.) wt.% of PS30-PAA36 in Dioxane R = 0.90 R = 0.97 R = Water Content (wt.%) w t % jumps w t% jumps 5w t% jumps 7w t% jumps Li ( % j ) Li ( % j )

71 Length Segregation of Corona Chains Decreases Vesicle Sizes PS 300 -b-paa PS 30 -b-paa 8 PS 300 -b-paa 75 Terreau, O.; Luo, L.; Eisenberg, A. Langmuir 003, 9,

72 Effect of Corona Bloc Polydispersity on Sizes of Vesicles Made from Polystyrene-b-Poly(acrylic acid) Average Vesicle Diameter (nm) PAA Chain Polydispersity Dynamic Light Scattering Tansmission Electron Microscopy Solvent content, number average molecular weight, and polymer concentration were ept constant. Terreau, O.; Luo, L.; Eisenberg, A. Langmuir 003, 9,

73 n Next: filling and release

74 What s DXR DXR.HCl: doxorubicin hydrochloride Anti-cancer drug Molecular weight = 580 (g/mol) Water soluble (50 mg/ml)

75 Active Loading into Vesicles Use vesicles as model carriers for Doxorubicin Induce loading by creating a transmembrane ph gradient ph =.5 ph = 6.3

76 Active vs. Passive Loading ph =.5 ph = 6.3 vs. ph =.5 ph =.5 ΔpH 4 ΔpH = 0 As a function of the wall permeability (addition of dioxane as a plasticizer)

77 Solvent content in the PS 00 -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.

78 Active vs. Passive Loading 0 Loading Efficiency 00 ph =.5 % moles load Dioxane content (% w/w) ph = 6.3 ph =.5 ph =.5 Vesicles prepared from PS 30 -b-paa 36 Common solvent: dioxane

79 Loading Mechanism = XNH + = XNH + 3 : neutral form is permeable : protonated form is NOT permeable + ph =.5 ph = 6.3

80 Release of DOX from PS 30 -b-paa 36 vesicles 0 8 0% dioxane/ 00% water 5% dioxane/ 75% water 50% dioxane/ 50% water Q (moles/ cm )/ x 0-9) Time (seconds) / Lim Soo, P.; Choucair, A.; Eisenberg, A.; In Press

81 Excitation spectra of 8-hydroxypyrene-,3,6-trisulphonate (HPTS) Intensity (CPS) X A Wavelength (nm)

82 Calibration profiles of HPTS curves were taen as I 454 /I 403 or I 403 /I 454 vs. ph. 300 B 4 3 I 403 /I I 454 /I ph

83 Time evolution of fluorescence excitation spectra from vesicle solutions with added HPTS at different dioxane contents; A: 0 wt%; B: 7 wt%; C: 4 wt%; D: 8 wt%; E: 40 wt%;..0 0% 7% 4% 8% 0 h 40% 0 h Intensity (a.u.) A h 44 h 0 h h 365 h 056 h B h 0 h C 3 h 5 h 9 h 46 h 9 h 40 h 65, 338 h D h 0 h 43 & 70 h /4 h 3, 6, 3 h E Wavelength (nm) Wavelength (nm) Wavelength (nm) Wavelength (nm) Wavelength (nm)

84 8. 40% 7% % [H + ] x [H + ]x % t / 7% 0 0% t / Plots of proton concentration [H + ] against the square root of diffusion time t.

85 4 log[d*(φ)/d*(7%)] dioxane content in solution (%) Plot of log[d * (Φ)/D * (7%)] against dioxane content.

86 Vesicles Summary () 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 bloc, relative bloc length, polydispersity, etc Part of a morphological continuum spheres rods vesicles Kinetics and mechanisms of transitions are nown Vesicle curvature stabilized by chain segregation: Longer chains outside, shorter chains inside. Segregation is size dependent and reversible.

87 Vesicles Summary () Interface compositions can be controlled by using dibloc mixtures, for example: PS-b-PAA with PS-b-PVP. Vesicles with opposite interfaces from ABC triblocs (PAA-b-PS-b-PVP) Triggered inversion is possible. Wall thicness is controllable (Small molecules inside vesicles) (Active loading is possible. Release occurs by diffusion) (Wall permeability can be controlled (by 00x))

88 F. LIU N. DUXIN

89 PARTING IS SUCH SWEET SORROW

90