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Self-Assembly and pH-Responsiveness of ABC Miktoarm Star Terpolymers K. Van Butsele,† C. A. Fustin,‡ J. F. Gohy,‡ R. Je´roˆme,† and C. Je´roˆme*,† Center for Education and Research on Macromolecules, UniVersite´ de Lie`ge, B6 Sart-Tilman, B-4000 Liege, Belgium and Unite´ CMAT, UniVersite´ Catholique de LouVain, Place Pasteur 1, 1348 LouVain-la-NeuVe, Belgium ReceiVed July 31, 2008. ReVised Manuscript ReceiVed October 15, 2008 This work deals with the self-assembly in water of ABC miktoarm star terpolymers consisting of hydrophobic poly(-caprolactone), hydrophilic poly(ethylene oxide) (PEO), and pH-sensitive poly(2-vinylpyridine) (P2VP). A variety of experimental techniques were used, including dynamic light scattering, transmission electron microscopy, and zeta potential. Special attention was paid to the pH dependency of the supramolecular self-assemblies. A key observation is the capability of the miktoarm terpolymers to form micelles stable over the whole range of pH, although a transition was observed from neutral to highly positively charged nanoobjects upon decreasing pH.
Introduction Because of great potential in a variety of fields, such as detergency, emulsions, drug delivery systems, and dispersions,1-5 much attention is currently paid to amphiphilic block copolymers and their properties in aqueous solution. Typically, they form micelles in water above a so-called critical micellar concentration (cmc). The mutual repulsion of the constitutive blocks results in a microphase separation and formation of self-assembled structures with a characteristic size in the range from ca. 10 to 100 nm. Although the micellar nanoobjects are usually spherical with a core formed by the nonsoluble blocks surrounded by a corona of the solvated chains,6,7 other types of micelles, such as rods and vesicles, can be formed under specific conditions.8-10 It must be kept in mind that whenever the insoluble blocks are of high molecular weight and/or of high Tg, micellization cannot occur directly in water. This drawback can however be avoided by the temporary use of a water-miscible organic solvent, common to all of the constitutive blocks.6,7 As a rule, the molecular architecture of block copolymers has a decisive impact on the shape of the micelles whatever the selective solvent, organic solvents11 or water.12,13 For example, AB diblocks14-16 form generally fairly small spherical micelles with a core protected by a shell of solvated blocks, while ABA * Towhomcorrespondenceshouldbeaddressed.E-mail:
[email protected]. † Universite´ de Lie`ge. ‡ Universite´ Catholique de Louvain. (1) Alexandridis, P.; Lindman, B., Eds. Amphiphilic Block Copolymers: SelfAssembly and Applications; Elsevier: Amsterdam, 2000. (2) Jones, M. C.; Leroux, J. C. Eur. J. Pharm. Biopharm. 1999, 48, 101–111. (3) Kataoka, K.; Harada, A.; Nagasaki, Y. AdV. Drug DeliVery ReV. 2001, 47, 113–131. (4) Torchilin, V. P. Cell. Mol. Life Sci. 2004, 61, 2549–2559. (5) Van Butsele, K.; Jerome, R.; Jerome, C. Polymer 2007, 48, 7431–7443. (6) Riess, G. Prog. Polym. Sci. 2003, 28, 1107–1170. (7) Gohy, J.-F. AdV. Polym. Sci. 2005, 190, 65–136. (8) Liu, F.; Eisenberg, A. J. Am. Chem. Soc. 2003, 125, 15059–15064. (9) Cameron, N. S.; Corbierre, M. K.; Eisenberg, A. Can. J. Chem. 1999, 77, 1311–1326. (10) Zhang, L.; Eisenberg, A. Polym. AdV. Technol. 1998, 9, 677–699. (11) Liu, T.; Liu, L. Z.; Chu, B. Amphiphilic Block Copolymers 2000, 115– 149. (12) Tuzar, Z. NATO ASI Ser., Ser. E: Appl. Sci. 1996, 327, 309–318. (13) Hamley, I. The Physics of Block Copolymers; Oxford Science Publications: Oxford, 1998. (14) Booth, C.; Yu, G. E.; Nace, V. M. Amphiphilic Block Copolymers 2000, 57–86. (15) Jada, A.; Hurtrez, G.; Siffert, B.; Riess, G. Macromol. Chem. Phys. 1996, 197, 3697–3710.
triblocks in a selective solvent for the B blocks form flower-like micelles in dilute solutions and a physical gel at higher concentrations.17-20 Recently, micellization of block copolymers with a complex architecture was studied, particularly that one of star-shaped block copolymers of the types AB2, AB3, and A2B2. Compared to the linear AB and ABA counterparts,21-25 their micellization is less favorable with a considerably lower association number. Combination of three chemically different blocks in one copolymer is an additional lever to manipulate the process of self-assembly.25,26 In a nonsolvent of the A block, linear ABC triblocks self-organize into core-shell-corona micelles with a core of A blocks surrounded by a layered shell of B and C blocks. When the central block B is insoluble, Janus micelles can be formed as a result of the lateral segregation of the soluble A and C blocks.27-34 Micellization of ABC miktoarm star terpolymers has been scarcely studied until now. Obviously, the mandatory (16) Zhang, L.; Khougaz, K.; Moffitt, M.; Eisenberg, A. Amphiphilic Block Copolymers 2000, 87–113. (17) Balsara, N. P.; Tirrell, M.; Lodge, T. P. Macromolecules 1991, 24, 1975– 1986. (18) Resendes, R.; Massey, J. A.; Temple, K.; Cao, L.; Power-Billard, K. N.; Winnik, M. A.; Manners, I. Chem. Eur. J. 2001, 7, 2414–2424. (19) Castelletto, V.; Hamley, I. W.; Ma, Y.; Bories-Azeau, X.; Armes, S. P.; Lewis, A. L. Langmuir 2004, 20, 4306–4309. (20) Liu, T.; Kim, K.; Hsiao, B. S.; Chu, B. Polymer 2004, 45, 7989–7993. (21) Sotiriou, K.; Nannou, A.; Velis, G.; Pispas, S. Macromolecules 2002, 35, 4106–4112. (22) Pispas, S.; Hadjichristidis, N. Macromolecules 2000, 33, 1741–1746. (23) Tsitsilianis, C.; Voulgaris, D.; Stepanek, M.; Podhajecka, K.; Prochazka, K.; Tuzar, Z.; Brown, W. Langmuir 2000, 16, 6868–6876. (24) Meier, M. A. R.; Gohy, J.-F.; Fustin, C.-A.; Schubert, U. S. J. Am. Chem. Soc. 2004, 126, 11517–11521. (25) Hadjichristidis, N.; Iatrou, H.; Pitsikalis, M.; Pispas, S.; Avgeropoulos, A. Prog. Polym. Sci. 2005, 30, 725–782. (26) Fustin, C. A.; Abetz, V.; Gohy, J. F. Eur. Phys. J. E 2005, 16, 291–302. (27) Patrickios, C. S.; Hertler, W. R.; Abbott, N. L.; Hatton, T. A. Macromolecules 1994, 27, 930–937. (28) Patrickios, C. S.; Lowe, A. B.; Armes, S. P.; Billingham, N. C. J. Polym. Sci., Part A: Polym. Chem. 1998, 36, 617–631. (29) Gohy, J.-F.; Willet, N.; Varshney, S. K.; Zhang, J.-X.; Jerome, R. e-Polym. 2002, Paper No. 35. (30) Erhardt, R.; Zhang, M.; Boeker, A.; Zettl, H.; Abetz, C.; Frederik, P.; Krausch, G.; Abetz, V.; Mueller, A. H. E. J. Am. Chem. Soc. 2003, 125, 3260– 3267. (31) Erhardt, R.; Boeker, A.; Zettl, H.; Kaya, H.; Pyckhout-Hintzen, W.; Krausch, G.; Abetz, V.; Mueller, A. H. E. Macromolecules 2001, 34, 1069–1075. (32) Xu, H.; Erhardt, R.; Abetz, V.; Mueller, A. H. E.; Goedel, W. A. Langmuir 2001, 17, 6787–6793. (33) Liu, Y.; Abetz, V.; Mueller, A. H. E. Macromolecules 2003, 36, 7894– 7898.
10.1021/la802469c CCC: $40.75 2009 American Chemical Society Published on Web 12/08/2008
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Table 1. DLS Data for a Series of (PEO)(P2VP)(PCL) Miktoarm Star Terpolymers
1a 1b 1c 1d 1e 1f
samplea
Dh,app (nm)b
µ2/Γ2c
(PEO140)(P2VP34)(PCL2) (PEO159)(P2VP41)(PCL7) (PEO114)(P2VP58)(PCL9) (PEO124)(P2VP14)(PCL16) (PEO146)(P2VP37)(PCL19) (PEO129)(P2VP43)(PCL17)
54 59 70 44 55 68
0.30 0.29 0.26 0.11 0.19 0.10
HLBd
Dh,app (nm) after NaOH additionb
19.5 18.7 18.3 15.8 16.5 16.8
25 27 26 37 39 42
µ2/Γ2c
HLB after NaOH additiond
size decrease (%)
0.17 0.16 0.29 0.15 0.12 0.22
12.4 11.6 8.3 12.5 10.3 9.3
54 54 63 16 29 38
a The subscript numbers are average degrees of polymerization. b Apparent hydrodynamic diameter determined by the CONTIN analysis of the DLS data. Polydispersity index determined by the cumulant analysis of the DLS data. d Hydrophilic lipophilic balance (HLB) ) 20 × [1 - Mn(lipophilic)/Mn(total)], where Mn(lipophilic) is the molecular weight of the lipophilic block (Mn(lipophilic) ) Mn(PCL) when P2VP is protonated and Mn(lipophilic) ) Mn(PCL+P2VP) when P2VP is unprotonated) and Mn(total) is the molecular weight of the (PEO)(P2VP)(PCL) miktoarm star terpolymer. c
convergence of three immiscible blocks at one common junction point does not allow layered structures to be formed anymore. Dumas et al.35 reported a preliminary study of the micellization of a three-arm star copolymer of polystyrene (PS), polymethylmethacrylate (PMMA), and polyethylene oxide (PEO) in water. More recently, Lodge et al. reported on formation of multicompartment micelles by ABC miktoarm star terpolymers comprising a hydrocarbon block (polyethylethylene), a fluorocarbon block (polyperfluoropropylene oxide), and a water-soluble block (polyethylene oxide). New morphologies were observed with compartmentalized micellar cores in relation to the volume fraction of the constitutive different blocks.36-40 Last but not least, the proper choice of at least one block can impart very specific properties to the micelles, e.g., responsiveness to pH, temperature, and ionic strength. For instance, ionization of a weak polyacid (or polybase) block changes with pH and so does its water solubility, which is ultimately translated in the structure and properties of the self-assembled nanoobjects. Poly(2vinylpyridine) is a typical example of a block which is protonated and water soluble at low pH, whereas it is hydrophobic and soluble in organic solvents at pH higher than 4.8. This paper reports on the aqueous solution properties of novel pH-sensitive ABC miktoarm star terpolymers consisting of a hydrophobic poly(-caprolactone) block, a hydrophilic poly(ethylene oxide) block, and a pH-sensitive poly(2-vinylpyridine) block. Micellization was investigated in water in the whole pH range using a variety of experimental techniques, mainly dynamic light scattering, transmission electron microscopy, and zeta potential. This aqueous solution behavior was compared to that of a PEO-b-P2VP diblock with similar pH responsiveness but a different molecular architecture.
Materials and Methods Synthesis of ABC miktoarm star terpolymers (MPEO)(P2VP)(PCL) was reported elsewhere41 and required an appropriate combination of anionic and ring-opening polymerization techniques. The molecular compositions of the copolymers studied in this work are listed in Table 1. One PEO-b-P2VP diblock, formed as an intermediate compound in the synthesis of miktoarm star terpolymers (Table 2), was used as a reference in the micellization studies. Aqueous solutions of the (MPEO)(P2VP)(PCL) miktoarms were prepared as follows. (34) Gohy, J.-F.; Willet, N.; Varshney, S.; Zhang, J.-X.; Jerome, R. Angew. Chem., Int. Ed. 2001, 40, 3214–3216. (35) Lambert, O.; Reutenauer, S.; Hurtrez, G.; Dumas, P. Macromol. Symp. 2000, 161, 97–102. (36) Li, Z.; Kesselman, E.; Talmon, Y.; Hillmyer, M. A.; Lodge, T. P. Science 2004, 306, 98–101. (37) Li, Z.; Hillmyer, M. A.; Lodge, T. P. Macromolecules 2006, 39, 765–771. (38) Li, Z.; Hillmyer, M. A.; Lodge, T. P. Nano Lett. 2006, 6, 1245–1249. (39) Lodge, T. P.; Rasdal, A.; Li, Z.; Hillmyer, M. A. J. Am. Chem. Soc. 2005, 127, 17608–17609. (40) Li, Z.; Hillmyer, M. A.; Lodge, T. P. Langmuir 2006, 22, 9409–9417. (41) Van Butsele, K.; Stoffelbach, F.; Jerome, R.; Jerome, C. Macromolecules 2006, 39, 5652–5656.
Table 2. DLS Data for the P2VP37-b-PEO146 Copolymer
Dh,app (nm)a
µ2/Γ2b
Dh,app (nm) after NaOH additiona
3.5/63
0.31
35
µ2/Γ2b 0.36
a
Apparent hydrodynamic diameter determined by the CONTIN analysis of the DLS data. b Polydispersity index determined by the cumulant analysis of the DLS data.
A 300 µL amount of hydrochloric acid (HCl, 1 M) was diluted by 20 mL of water (MilliQ) and added to 5 mL of a copolymer solution (1 wt%) in N,N-dimethylformamide (DMF) under vigorous stirring for 2 h. The micellar solutions were then dialyzed against 1 L of water through cellulose dialysis membranes (Spectra por, cutoff 3500). Complete removal of DMF was confirmed by NMR spectroscopy of the micelles after dialysis for a minimum of 16 h within a precision of 5%. Micelles were accordingly formed with protonated P2VP (63% protonation). Next, the deprotonated counterparts were prepared by addition of a NaOH solution and dialysis against water for 24 h. Micellar solutions of the PEO-bP2VP diblock were similarly prepared. Dynamic Light Scattering. Dynamic light scattering (DLS) data were collected with a Malvern CGS-3 equipped with a He-Ne laser (633 nm) at 90°. A bath of filtered toluene surrounded the scattering cell, and the temperature was kept constant at 25 °C. The polydispersity index (PDI) of the micelles was estimated from the µ2/Γ2 ratio, where Γ and µ2 are the first and second cumulant, respectively. The experimental data have been also analyzed by the CONTIN method, based on an inverse-Laplace transformation of the data, leading to a size distribution histogram and the apparent hydrodynamic diameter. Zeta-Potential Measurements. The micellar solutions were analyzed by electrophoresis at 20 °C with a Zetasizer 2000 from Malvern Instruments. The zeta potential (ξ) was calculated from the electrophoretic mobility (U) according to the U ) ξ/η relationship, where is the dielectric constant and η is the solution viscosity. Transmission Electron Microscopy. Transmission electron microscopy (TEM) was performed with a Philips CM-100 microscope operating at 100 kV. TEM micrographs were directly recorded with a Gatan 673 CCD camera, and data were transferred to a computer equipped with Kontron KS 100 software. Samples were prepared by spin coating a drop of 0.1 wt % aqueous micellar solution onto a Formvar-coated copper grid. Potentiometric Titration. A micellar solution of the (PEO)140(P2VP)34(PCL)2 ABC miktoarm star terpolymer (1 mg/ mL, pH 7) was titrated by the dropwise addition of 10-2 M HCl. The solution pH was monitored with a Consort 932 pH meter. Nuclear Magnetic Resonance Spectroscopy. 1H NMR (400 MHz) spectra were recorded with a Bruker AM 400 apparatus in D2O at 25 °C.
Results and Discussion Except for the PEO146-b-P2VP37 diblock and the (PEO)140(P2VP)34(PCL)2 ABC miktoarm copolymers all copolymers investigated in this work could not be directly dissolved in water.
ABC Miktoarm Star Terpolymers
Figure 1. Distribution function of the micellar diameter for the PEO146b-P2VP37 diblock copolymer (a) with protonated P2VP and (b) with deprotonated P2VP after NaOH addition.
Therefore, they were first dissolved in a water-miscible organic solvent (1 wt %) common to the three blocks followed by addition of water (pH ) 2) until micelles were formed. After dialysis against water micelles with protonated P2VP blocks were collected and characterized at a constant 1 mg/mL concentration. This concentration was indeed higher than the critical micellar concentration (cmc) that was measured by the classical fluorescent method using pyrene42 (see Supporting Information) and found to be 9 × 10-6 mol/L for the (PEO)140(P2VP)34(PCL)2 ABC miktoarm star terpolymer that contained the shorter hydrophobic PCL block. The cmc of the other terpolymers was expectedly lower.43 Micellization of the (PEO)140(P2VP)34(PCL)2 ABC Miktoarm Star Terpolymer. In a preliminary step a PEO146-bP2VP37 diblock copolymer, whose composition and molecular weight are very close to the diblock precursor of the miktoarm star terpolymer under consideration, was studied in water by dynamic light scattering as a function of pH. At low pH the P2VP block is protonated and thus hydrophilic, whereas it is unprotonated and hydrophobic at high pH. It was therefore expected that the diblock copolymer would be completely soluble in acidic media and form micelles only at high pH. However, dynamic light scattering showed that partial aggregation occurred at low pH (pH ) 3) (Figure 1a). According to the CONTIN analysis of the intensity autocorrelation function two populations of scattering objects coexist with a apparent hydrodynamic diameter of Dh,app,1 ) 3-5 nm and Dh,app,2 ≈ 60 nm, respectively (Table 2). The minor population of very small objects can be assigned to free polymer chains, and the second population is typical of loose aggregates as exhibited by P2VP homopolymer at low pH range (pH ) 1-4) as a result of complex and partial ionization of the chains and possible hydrophobic interactions of uncharged segments.44,45 At pH higher than 5 the scattered intensity increased significantly and only one population was detected (Dh,app ) 35 nm) (Figure 1b) in agreement with formation (42) Wilhelm, M.; Zhao, C. L.; Wang, Y.; Xu, R.; Winnik, M. A.; Mura, J. L.; Riess, G.; Croucher, M. D. Macromolecules 1991, 24, 1033–1040. (43) Vangeyte, P.; Leyh, B.; Heinrich, M.; Grandjean, J.; Bourgaux, C.; Jerome, R. Langmuir 2004, 20, 8442–8451. (44) Gohy, J.-F.; Antoun, S.; Jerome, R. Macromolecules 2001, 34, 7435– 7440. (45) Vamvakaki, M.; Papoutsakis, L.; Katsamanis, V.; Afchoudia, T.; Fragouli Panagiota, G.; Iatrou, H.; Hadjichristidis, N.; Armes Steve, P.; Sidorov, S.; Zhirov, D.; Zhirov, V.; Kostylev, M.; Bronstein Lyudmila, M.; Anastasiadis Spiros, H. Faraday Discuss 2005, 128, 129–147.
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Figure 2. Distribution function of the micellar diameter for the (PEO146)(P2VP37)(PCL19) miktoarm star terpolymer (sample 1e in Table 1) (a) with protonated P2VP and (b) with deprotonated P2VP after NaOH addition. Scheme 1
of micelles consisting of a deprotonated P2VP core and a corona of hydrated PEO chains.46 Micellization of the (PEO)140(P2VP)34(PCL)2 miktoarm star terpolymer was then analyzed by DLS. Compared to the PEO146b-P2VP37 diblock the scattered intensity was significantly higher at low pH and only one population of particles was detected (Figure 2a) in the CONTIN histogram. Therefore, in contrast to the PEO146-b-P2VP37 precursor the (PEO)140(P2VP)34(PCL)2 miktoarm star terpolymer is able to form micelles in acidic solutions. This different behavior can be ascribed to the presence of the hydrophobic PCL block in the ABC miktoarm star terpolymer. This PCL block is expected to aggregate into hydrophobic cores that are surrounded by hydrophilic PEO and protonated P2VP coronal chains in acidic media (Scheme 1) resulting in formation of true micelles with a denser and dehydrated core rather than loose aggregates like in the case of the PEO-b-P2VP diblock copolymer. It is remarkable to note that such micelles are already observed for the ABC miktoarm star terpolymer with a PCL block of DP as small as 2 (Table 1, sample 1a). A positive ξ potential (12.5 ( 5 mV) is clear evidence for ionized P2VP segments located at the periphery of the micelles. Spherical micelles were observed by TEM with a diameter of about 37 nm (Figure 3A). This size is smaller than Dh,app (54 nm) measured by DLS merely because the corona is dehydrated when the micelles are observed by TEM. To highlight the pH sensitivity of the micelles the pH was increased by addition of NaOH (10-2 M) followed by dialysis in order to eliminate any excess and the NaCl byproduct. Complete collapse of the P2VP block was confirmed by TEM that showed (46) Gohy, J.-F.; Varshney, S. K.; Antoun, S.; Jerome, R. Macromolecules 2000, 33, 9298–9305.
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Figure 4. Titration curve of the (PEO140)(P2VP34)(PCL2) micelles (sample 1a in Table 1).
Figure 3. TEM micrographs of micelles formed by the (PEO140)(P2VP34)(PCL2) miktoarm star terpolymer micelles (sample 1a in Table 1) in water with (A) protonated P2VP and (B) deprotonated P2VP.
spherical particles with a diameter of 20 nm (Figure 3b) instead of 37 nm at low pH. This observation strongly suggests that the protonated (P2VP)34 blocks are longer than the (PEO)140 blocks, although their average DP is smaller. The stretching of the P2VP chains upon ionization, as result of internal electrostatic repulsions, might be a reasonable explanation. Indeed, the end-to-end distance has been estimated for fully stretched P2VP chains with a DP of 3447,48 and PEO chains with a DP of 140 (random coil conformation).49-51 These distances are 8.5 nm for ionized P2VP34 and 5.9 nm for PEO140. Consistently, the ξ potential drops from +12.5 ((5 mV) down to -5 mV ((5 mV) and thus close to zero upon P2VP deprotonation. The positively charged P2VP that was exposed at the micelles surface in acidic media thus disappeared at high pH at the benefit of the neutral PEO. Figure 4 shows the titration curve for the ABC miktoarm star terpolymer in aqueous solution. Because of the constitutive tertiary amines of P2VP this block of the miktoarm star terpolymer participates in an acid-base equilibrium. The experimental curve (47) Roiter, Y.; Minko, S. J. Am. Chem. Soc. 2005, 127, 15688–15689. (48) Puterman, M.; Kolpak, F. J.; Blackwell, J.; Lando, J. B. J. Polym. Sci., Polym. Phys. Ed. 1977, 15, 805–819. (49) Jayachandran, K. N.; Maiti, S.; Chatterji, P. R. Polymer 2001, 42, 6113– 6118. (50) Gao, W.-P.; Bai, Y.; Chen, E.-Q.; Li, Z.-C.; Han, B.-Y.; Yang, W.-T.; Zhou, Q.-F. Macromolecules 2006, 39, 4894–4898. (51) Brandrup, J.; Immergut, E. H., Grulke, E. A., Eds. Polymer Handbook, 4th ed.; Wiley: New York, 1998.
of Figure 4 is similar to the one reported by Martin et al.52 for a PEO-b-P2VP diblock copolymer. Analysis of these data agrees with a pKa of about 5.0 for the terpolymer under consideration, in very good agreement with a pKa of P2VP.46,52 The 1H NMR spectra for the micelles formed by the ABC miktoarm star terpolymer at low and high pHs are shown in Figure 5. At low pH (pH 3) (Figure 5a), in addition to the signal for the PEO protons at 3.6 ppm, the P2VP protons are clearly observed at 6.3-8.3 and 1.8-2.2 ppm, quite consistent with hydration of the P2VP block. At high pH (pH 7, adjusted with NaOH), all of the P2VP resonance peaks have completely disappeared and only the -CH2CH2- protons of the PEO block persist at 3.6 ppm, in agreement with the pH sensitivity of the micelles and collapse of the P2VP blocks. The protons of the PCL blocks are not visible, as expected considering the solid environment in the micellar core. Influence of the Composition of (PEO)(P2VP)(PCL) ABC Miktoarm Star Terpolymers on Micellization. Additional miktoarm star terpolymers with PCL and P2VP blocks of different lengths were synthesized as reported in Table 1. Except for sample 1d which is borderline, the degree of polymerization of P2VP is such that the ionized and thus stretched conformation exceeds that one of the random coil conformations of PEO. It is thus not surprising that the micellar apparent diameter increases significantly with the length of the P2VP block at low pH and constant PEO and PCL block lengths (Table 1, samples 1d and 1f). It is therefore clear that the micellar size is basically controlled by the length of the positively charged P2VP. As a rule deprotonation of P2VP results in contraction of the micelles (e.g., from 70 to 26 nm for sample 1c in Table 1), although no precipitation occurs whatever the copolymer composition that covers a large HLB range (from 18.3 to 8.3). Even if smaller, a size decrease is still observed when the length of the ionized P2VP block is comparable (slightly smaller) to the PEO block (Table 1, sample 1d). This observation suggests that the PEO chains are not in a random coil conformation at low pH but are rather stretched as a result of repulsion with the charged P2VP blocks also part of the corona. Collapse of the P2VP block (one-half of the chains of the corona) allows the stretched PEO chains to relax leading to the small contraction of the micelles (reduction of the apparent diameter from 44 to 37 nm). It is interesting to mention that the apparent hydrodynamic diameter observed at high pH for copolymer 1d (52) Martin, T. J.; Prochazka, K.; Munk, P.; Webber, S. E. Macromolecules 1996, 29, 6071–6073.
ABC Miktoarm Star Terpolymers
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Figure 5. NMR spectra for the (PEO140)(P2VP34)(PCL2) micelles (sample 1a in Table 1) in D2O with (a) protonated P2VP and (b) deprotonated P2VP. Table 3. Hydrodynamic Diameter Extrapolated at Zero Concentration and Zero Angle for (PEO)(P2VP)(PCL) Miktoarm Star Terpolymer
1c 1d
sample
Dh (nm)
Dh (nm) after NaOH addition
(PEO114)(P2VP58)(PCL9) (PEO124)(P2VP14)(PCL16)
33 28
13 18
is close to that measured for a PEO114-b-PCL16 diblock (Dh,app ) 34.5 nm)53 whose block lengths are very similar to the miktoarm star terpolymer. Expectedly, when the P2VP block is neutral and thus collapsed the size of the micelles increases with the length of the PCL block at constant PEO and P2VP blocks (Table 1, samples 1a and 1e) as would happen in micellization of PEOb-PCL diblock copolymers.53 The real hydrodynamic diameter was measured for the two extreme samples, i.e., the samples showing the largest (sample 1c) and smallest (sample 1d) change in size upon pH variation. The real Dh were obtained by performing the measurements at different angles (from 40° to 150°) and different concentrations (from 0.5 to 2.5 g/L) and extrapolating to zero concentration and zero angle (Table 3). These Dh are smaller than the apparent hydrodynamic diameters but lead to the same conclusions as that previously drawn from the apparent Dh. In the series of the miktoarm star terpolymers investigated in this study the size of the corona and thus of the micelles formed in water at low pH is dominated by the charged P2VP block which is systematically longer than the PEO one. This situation makes the micelles sensitive to pH as expressed by a significant decrease in the micellar size upon increasing pH. When deprotonated the P2VP blocks leave the corona and contribute to the size of the core together with PCL. (53) Vangeyte, P.; Gautier, S.; Jerome, R. Colloids Surf., A 2004, 242, 203– 211.
Conclusions The pH-responsive (PEO)(P2VP)(PCL) miktoarm star terpolymers investigated in this study form spherical micelles that exhibit several key characteristic features. Because they contain a weak polybase block (P2VP) they are responsive to pH. As long as this block is charged at low pH and longer than the PEO block the size of the micelles decreases dramatically when the pH is increased, e.g., from 70 to 26 nm for the (PEO114)(P2VP58)(PCL9) miktoarm star terpolymer. In parallel, the micelles expose positive charges to water at low pH, whereas they are neutral at high pH, PEO being the single component of the corona. This situation is quite attractive because PEO is known for making micelles stealthy54 and nonadhesive toward surfaces. Finally, whatever the location of the P2VP blocks, in the core or in the corona, and thus whatever the size and charge of the micelles, these micelles are stable in the whole range of pH. Interaction of these micelles with a negatively charged surface or a large volume increased of these micelles could thus be triggered by the simple lowering of the pH. They are thus quite promising for targeted drug delivery applications.55 Acknowledgment. The authors are grateful to the “Services Fe´de´raux des Affaires Scientifiques, Techniques et Culturelles” in the frame of the “Poˆles d’Attraction Interuniversitaires: VI27”. K.V.B. is grateful to the “Fonds pour la Formation a` la Recherche dans l’Industrie et dans l’Agriculture” (FRIA) for a fellowship. C.A.F. is a Research Associate of the FRS-FNRS. Supporting Information Available: Materials and methods for fluorimetric measurements. Plot of the dependence of the intensity of the first peak (I1) of the emission spectrum at 375 nm versus the logarithm of the copolymer concentration is presented. This material is available free of charge via the Internet at http://pubs.acs.org. LA802469C (54) Vermette, P.; Meagher, L. Colloids Surf., B 2003, 28, 153–198. (55) Lee, E. S.; Na, K.; Bae, Y. H. Nano Lett. 2005, 5, 325–329.
