2066
Langmuir 2004, 20, 2066-2068
Colloidal Stability of Aqueous Dispersions of Block Ionomer Complexes: Effects of Temperature and Salt Sergey V. Solomatin,† Tatiana K. Bronich,† Adi Eisenberg,‡ Victor A. Kabanov,§ and Alexander V. Kabanov*,† Department of Pharmaceutical Sciences, College of Pharmacy, 986025 Nebraska Medical Center, Omaha, Nebraska 68198-6025, Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec, Canada H3A 2K6, and Department of Polymer Sciences, School of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory, Moscow V-234, 119899 Russia Received May 23, 2003. In Final Form: January 6, 2004 This work characterized colloidal stability of the dispersions, formed by the complexes of poly(ethylene oxide)-b-poly(sodium methacrylate) and hexadecyltrimethylammonium bromide. At room temperature, the dispersion was stabilized by the poly(ethylene oxide) (PEO) chains and did not aggregate for at least several months. Elevation of temperature caused aggregation of the dispersion because of dehydration of the PEO chains. At initial stages (minutes), the aggregation was reversible and the particles spontaneously redispersed once the temperature was decreased. However, it became irreversible at the later stages (hours), probably indicating fusion of the hydrophobic cores of the BIC particles. Addition of elementary salts led to a decrease of the aggregation temperature. The effects of various salts were dependent on the chemical nature of the ions and were consistent with the Hofmeister series. This behavior was discussed in terms of hydration and London (dispersion) interactions between the ions and the PEO.
Introduction Block ionomer complexes (BIC) are produced by mixing aqueous solutions of ionic surfactants and block copolymers of the special type, termed “block ionomers”.1 Each molecule of block ionomer contains an ionic polymer block and nonionic water-soluble polymer block, usually poly(ethylene oxide) (PEO). Interaction of the ionic polymer blocks and surfactant ions, which are oppositely charged, leads to mutual charge neutralization and formation of hydrophobic domains. However, even at stoichiometric compositions, which correspond to complete charge neutralization, macroscopic phase separation does not develop and stable aqueous dispersions of BIC are formed.2-4 Since the stoichiometric complexes of surfactants with homopolyelectrolytes usually precipitate, stability of BIC in dispersion was attributed to the effect of the PEO chains forming a hydrophilic “corona”.5 The aggregation behavior of PEO-stabilized colloids can be affected by the changes in the temperature and concentration of elementary salts.6 This paper characterizes the effects of these parameters on the colloidal stability of the BIC formed by poly(ethylene oxide)-b-poly(sodium methacrylate) (PEO-b-PMA) copolymer and hexadecyltrimethylammonium bromide (HTAB). The results are useful in view of increasing attention to BIC as potential drug delivery vehicles.7
Experimental Section Materials. PEO210-b-PMA97 block copolymer (numbers in lower register indicate the polymerization degrees of the blocks) was synthesized as described previously.8,9 HTAB and inorganic salts (Sigma-Aldrich) were used without further purification. Methods. Preparation and characterization of the BIC was described in the previous publication.8 Effective hydrodynamic particle diameters (Deff) and ζ-potentials were determined by dynamic light scattering.8 Aggregation processes were monitored by photometric technique using Shimadzu UV-160 spectrophotometer with thermostatic cells. Changes in turbidity were monitored by measuring the optical density at 420 nm (A420).
e-mail:
Results and Discussion BIC Dispersions at Low Salt Concentration. At room temperature, BIC formed stable dispersions of nanoscale-size (Deff ) 80 ( 10 nm) electroneutral (ζpotential ) 0 ( 5mV) particles. Both parameters did not display any significant changes within the course of several months, which suggests steric stabilization of the particles by the PEO corona. Solvation of the corona is one of the major factors responsible for the steric stabilization.6 Its desolvation in the vicinity of the θ-temperature should lead to aggregation.10-13 PEO dehydrates upon increase of the temperature14,15 and has the θ-temperature in water in the range of 92-99 °C.16-18 Therefore, one would expect aggregation of the BIC dispersion within this temperature range.
(1) Kabanov, A. V.; Bronich, T. K.; Kabanov, V. A.; Yu, K.; Eisenberg, A. Macromolecules 1996, 29, 6797. (2) Bronich, T. K.; Kabanov, A. V.; Kabanov, V. A.; Yu, K.; Eisenberg, A. Macromolecules 1997, 30, 3519. (3) Kabanov, A. V.; Bronich, T. K.; Kabanov, V. A.; Yu, K.; Eisenberg, A. J. Am. Chem. Soc. 1998, 120, 9941. (4) Bronich, T. K.; Popov, A. M.; Eisenberg, A.; Kabanov, V. A.; Kabanov, A. V. Langmuir 2000, 16, 481. (5) Kabanov, A. V.; Vinogradov, S. V.; Suzdaltseva, Yu. G.; Alakhov, V. Yu. Bioconjugate Chem. 1995, 6, 639. (6) Napper, D. H. Polymeric stabilization of colloidal dispersions; Academic Press: London, 1983.
(7) Self-assembling Complexes for Gene Delivery: From Laboratory to Clinical Trial; Kabanov, A. V., Felgner, P. L., Seymour, L. W., Eds.; John Wiley & Sons: Chichester, 1998. (8) Solomatin, S. V.; Bronich, T. K.; Eisenberg, A.; Bargar, T. W.; Kabanov, V. A.; Kabanov, A. V. Langmuir 2003, 19, 8069. (9) Wang, J.; Varshney, S. K.; Jerome, R.; Teyssie, P. J. Polym. Sci., Part A: Polym. Chem. 1992, 30, 2251. (10) Napper, D. H. J. Colloid Interface Sci. 1970, 32, 106. (11) Evans, R.; Napper, D. H. J. Colloid Interface Sci. 1975, 52, 260. (12) Clarke, J.; Vincent, B. J. Chem. Soc., Faraday Trans. 1 1981, 77, 1831. (13) Croucher, M. D.; Hair, M. L. J. Colloid Interface Sci. 1981, 81, 257. (14) Bailey, F. E., Jr.; Koleske, J. V. Poly(ethylene oxide); Academic Press: New York, 1976.
* Corresponding author. Fax: (402) 559-9543;
[email protected]. † University of Nebraska Medical Center. ‡ McGill University. § Moscow State University.
10.1021/la034895f CCC: $27.50 © 2004 American Chemical Society Published on Web 02/17/2004
Colloidal Stability of Aqueous Dispersions
Figure 1. The effect of temperature on turbidity of the BIC dispersion. CBIC ) CHTAB ) CPOMA(base-mole) ) 0.25 mM. The arrow indicates the cct, determined as the deflection point. The dash-arrow indicates the average PEO θ-temperature. The insert plot shows the cct at various BIC concentrations.
Figure 1 presents the turbidity of the BIC dispersion measured as a function of temperature. To eliminate the effect of heating rate, samples were equilibrated at each temperature for at least 10 min. At temperatures below 80 °C, the turbidity was very low (A420 < 0.1) and did not change during the equilibration time. Between 80 and 85 °C, the turbidity became noticeable (A420 > 0.1) and very slowly increased during the equilibration time. At 85 °C, increase of turbidity was rapid and a precipitate gradually formed. The deflection point on the turbidity curve, corresponding to the transition from “extremely slow” to “fast” aggregation, was 82 ( 1 °C. This temperature is denoted herein as the “critical coagulation temperature” (cct). Defined in such way, the cct is not a “true” critical coagulation temperature, but rather an operational, wellreproducible parameter. Only a couple of degrees below the cct any changes in the system occurred on an hour time scale or slower and were difficult to detect. The cct was well below the expected 92-99 °C range and, furthermore, it decreased as the dispersion concentration increased (see the insert in Figure 1), which probably indicates kinetically, rather than thermodynamically, controlled aggregation. Moreover, the aggregates redispersed spontaneously upon cooling to 25 °C within minutes after the aggregation onset (Deff ) 100 ( 15 nm, not a significant difference with the initial size). However, annealing the samples above the cct for several hours made the aggregation practically irreversiblesthe precipitate did not redisperse even upon vigorous stirring. This suggests that individual BIC particles gradually fuse into a macroscopic phase upon aggregation.19 BIC Dispersions at Moderate Salt Concentration. PEO solvation can be affected by addition of elementary salts. The θ-temperature and the lower critical solution temperature (LCST) of the PEO in aqueous solutions decreases, as the salt concentration increases.20,21 Figure 2 demonstrates that the cct also decreased from 80.5 °C (15) (a) Kjellander, R.; Florin, E. J. Chem. Soc., Faraday Trans. 1 1981, 77, 2053. (b) Karlstrom, G. J. Phys. Chem. 1985, 89, 4962. (c) Dormidontova, E. E. Macromolecules 2002, 35, 987. (d) Smith, G. D.; Bedrov, D. J. Phys. Chem. 2003, 107, 3095. (16) Fisher, V.; Borchard, W. J. Phys. Chem. B 2000, 104, 4463. (17) Boucher, E. A.; Hines, P. M. J. Polym. Sci., Polym. Phys. Ed. 1976, 14, 2241. (18) Ataman, M.; Boucher, E. A. J. Polym. Sci., Polym. Phys. 1982, 20, 1585. (19) Narrow polydispersity of the BIC particles and independence of their size upon the overall concentration and preparation route suggests that the dispersed state is stable. Although there is no definitive answer at this point, we believe that aggregated phase is metastable at the room temperature. (20) Bailey, F. E., Jr.; Callard, R. W. J. Appl. Polym. Sci. 1959, 1(1), 56. (21) Florin, E.; Kjellander, R.; Eriksson, J. C. J. Chem. Soc., Faraday Trans. 1 1984, 80, 2889.
Langmuir, Vol. 20, No. 6, 2004 2067
Figure 2. The effect of NaCl concentration on the cct of the BIC dispersion. CBIC ) CHTAB ) CPOMA(base-mole) ) 0.5 mM. Dashed line demonstrates the effect of NaCl on the LCST of the PEO, data points extracted from ref 21. Slope was determined as the change in the cct (in degrees) divided by the change in salt concentration (in moles/liter) for the linear parts of the curves. Table 1. Effect of the Salt Nature on the cct of the BIC salt, 0.15 M cct
s,
∆cct a
°Ca
) cct-ccts
LiCl
NaCl
KCl
NaF
NaBr
76 6
74 8
74 8
63 21
81.5 0.5
BIC concentration was 0.25 mM.
for the “salt-free”22 system to 65 °C in the presence of 0.15 M NaCl. Further increase in the salt concentration from 0.15 to 0.3 M NaCl resulted in the cct decreasing linearly with the slope of 29 °C/M. This value was very similar to the slope of the decrease of LCST of the PEO solution upon increase in the salt concentration (upper dashed line in Figure 2).21 This reinforces the relationship between the aggregation stability of the BIC and the PEO solvation. In other words, the depression of the cct observed within 0.1-0.3 M range of NaCl concentrations can be mostly attributed to the effect of the salt on the solvation of the PEO corona. A deviation of the cct from the linear dependence at CNaCl < 0.1 M NaCl indicates that other factors (e.g., ionic strength dependence of the BIC fusion kinetics) might also be important at low salt concentrations. Increase of the salt concentration above 0.4 M led to BIC disintegration because of screening of the electrostatic interactions.8 Disintegration was highly cooperative and proceeded within a narrow range of NaCl concentrations (0.42-0.47 M). The cct depended on the chemical nature of the salts. Table 1 presents the cct depressions produced by equivalent (0.15 M) concentrations of various monovalent salts. The potency of halides to depress cct decreased in the following order: NaF > NaCl > NaBr. Within this sequence, the cct depression effects differ by more than 20 °C. On the other hand, variation of the cation nature did not result in significant differences in the cct depression. Thus, the salt dependence of BIC dispersion stability follows the same pattern as that observed for salting-out of the PEO,20,21 as well as a variety of other organic compounds (proteins, polymers, alcohols). This pattern is known as the Hofmeister series. One common consideration of the salting-out effects accounts for the negative adsorption (exclusion) of salts from the water-solute interface regions.21,23-30 Salt exclusion increases the chemical potential of water at the (22) Strictly speaking, even in the absence of added salt the system is not completely “salt-free”, since counterions of both copolymer and surfactant (Na+ and Br-) are present. However, their concentrations (equal to the concentration of BIC, i.e., 0.5 mM and less) are much lower than the concentration of added electrolyte (100 mM and more). (23) Robinson, D. R.; Jencks, W. P. J. Am. Chem. Soc. 1965, 87, 2470. (24) Aveyard, R.; Heselden, R. J. Chem. Soc., Faraday Trans. 1 1975, 71, 312.
2068
Langmuir, Vol. 20, No. 6, 2004
Figure 3. The free-energy changes ion adsorption at the PEOwater interface. (a) Contributions of the image charge and polymer dehydration, ∆Uic+∆Upd. ∆Upd increased proportionally to the ion surface area: ∆Upd ) k‚ri2, where ri is ionic radius. ∆Uic was considered the same for all ions. (b) Contribution of dispersion interactions was estimated as ∆Udisp ) a*i‚IPi‚IPw/ (IPi + IPw),34 where a*i is excess polarizabilities of ions in aqueous solutions,35 IPi is ionization potentials of ions,36 IPw is ionization potential of water.34 The energy units in a and b are arbitrary and should not be directly compared.
interface relative to water in the bulk, therefore increasing the surface energy and favoring the aggregation of solutes. Differences in the salting-out potency among various salts are attributed to the extents of their exclusion: the greater the exclusion is the larger the potency is.31 To account for the differences in salt exclusion extents, one can consider the following contributions to free-energy changes ∆U for ion adsorption: (1) the image charge repulsion energy ∆Uic, (2) the PEO dehydration energy ∆Upd, and (3) the dispersion interactions energy ∆Udisp.32 The net ∆U is expressed by the sum of the three terms and positive values of ∆U favor ion exclusion:
∆U ) ∆Uic + ∆Upd + ∆Udisp The ∆Uic term depends only on the magnitude of the ion charge and should have the same positive value for all monovalent ions. The ∆Upd term includes the loss of solvation energy of PEO because of displacement of water molecules by the adsorbed ion, that is, it is always positive and increases, as the ionic size increases. The ∆Udisp term accounts for the stronger dispersion interactions of ions with the PEO than with water because of the larger electronic polarizability of the former (as estimated from refraction coefficients,33,34 nPEO ) 1.46, nH2O ) 1.33). The ∆Udisp is proportional to the excess polarizabilities of the ions relative to water: it is positive for ions that are less (25) Aveyard, R.; Salem, S. M. J. Chem. Soc., Faraday Trans. 1 1976, 72, 1609. (26) Garvey, M. J.; Robb, I. D. J. Chem. Soc., Faraday Trans. 1979, 75, 993. (27) Ninham, B. W.; Yaminsky, V. Langmuir 1997, 13, 2097. (28) Bostro¨m, M.; Williams, D. R.; Ninham, B. W. Langmuir 2001, 17, 4475. (29) Bostro¨m, M.; Williams, D. R.; Ninham, B. W. Langmuir 2002, 18, 6010. (30) Karraker, K. A.; Radke, C. J. Adv. Colloid Interface Sci. 2002, 96, 231. (31) Kabalnov, A.; Olsson, U.; Wennerstro¨m, H. J. Phys. Chem. 1995, 99, 6220. (32) As a result of unequal adsorption of co-ions and counterions, charge separation free-energy contribution ∆Uel might also appear. We omit it herein for simplicity reasons.
Solomatin et al.
polarizable than water and negative for ions that are more polarizable than water.27 Figure 3 relates the various free-energy contributions to the ionic radius. We did not determine the absolute values for each contribution but evaluated the trends in their changes and compared them with the salting-out effects. For K+ and F-, the ∆Udisp were negligible because their polarizabilities are practically equal to the polarizability of water. Thus, the interactions of these ions with the PEO-water interface were dominated by the positive ∆Uic + ∆Upd term. Large positive ∆U values for these ions were consistent with strong exclusion and strong saltingout effects. As the ionic radius and polarizability increased in the order F- < Cl- < Br-, the ∆Udisp decreased and offset the increase in the ∆Uic+ ∆Upd. The decrease in the net ∆U was consistent with the decrease in the saltingout effect observed experimentally. If this trend is continued, the ions more polarizable than Br- (e.g., I- or SCN-) could exhibit positive adsorption and salting-in behavior. Although such behavior could not be observed (NaI and NaSCN disintegrate BIC at very low concentrations because of tight binding of anions to the surfactant headgroups),8 I- or SCN- did produce salting-in effects in Pluronic systems.38 Two possible explanations can be suggested for the similar salting-out potencies of Li+, Na+, and K+. One is the compensation of the ∆Upd increase with the ∆Udisp decrease resulting in the net ∆U being constant. Another is high positive values of net ∆U (much larger than kT) for each of these cations, which would result in their complete exclusion from the interface and in achieving the same maximal salting-out effects. Conclusions BIC dispersions are stabilized by the PEO chains and their aggregation stability is strongly dependent on the PEO solvation. The cct values (below the θ-temperature) and their concentration dependence indicate contribution of kinetic factors to the aggregation process. Increase of the salt concentration in the dispersion causes the cct to decrease in a salt nature-dependent manner. This effect was discussed in terms of the negative adsorption of salts at the PEO-water interface region. The extent of the adsorption is determined by the balance between the hydration and dispersion forces. A practical conclusion is that the dispersion is stable in physiological conditions (0.15 M NaCl, 37 °C), which is important for the potential use of the BIC in pharmaceutics. Acknowledgment. The authors are grateful for the support of this work by NSF (DMR-0071682) and NSERC, Canada (STR-0181003). LA034895F (33) Bender, G. W.; LeGrand, D. G.; Gaines, G. L., Jr. Macromolecules 1969, 2, 681. (34) CRC Handbook of chemistry and physics; Lide, D. R., Frederikse, H. P. R., Eds.; CRC Press: Boca Raton, 1995. (35) Mahan, G. D. J. Chem. Phys. 1982, 76, 493. (36) Coker, H. J. Phys. Chem. 1976, 80, 2084 (37) Marcus, Y. Ion properties; Marcel Dekker: New York, 1997; Chapter 4. (38) (a) Pandya, K.; Lad, K.; Bahadur, P. Pure Appl. Chem. A 1993, 30, 1. (b) Alexandridis, P.; Holzwarth, J. F. Langmuir 1997, 13, 6074.
