Langmuir 1998, 14, 6101-6106
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Self-Assembly in Mixtures of Poly(ethylene oxide)-graft-Poly(ethyleneimine) and Alkyl Sulfates Tatiana K. Bronich,† Timothy Cherry,† Serguei V. Vinogradov,† Adi Eisenberg,‡ Victor A. Kabanov,§ and Alexander V. Kabanov*,† Department of Pharmaceutical Sciences, University of Nebraska Medical Center, 600 South 42nd Street, Omaha, Nebraska 68198-6025, Department of Polymer Sciences, M. V. Lomonosov, Moscow State University, Leninskie Gory, Moscow V-234, 119899 Russia, and Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, Quebec, Canada H3A 2K6 Received May 5, 1998. In Final Form: August 10, 1998 The complexes formed between the cationic graft copolymer of poly(ethylene oxide) and poly(ethyleneimine) (PEO-g-PEI) and alkyl sulfate surfactants were studied using potentiometric titration, fluorescence spectroscopy, ζ-potential measurement, dynamic light scattering, and electron microscopy. In contrast to the complexes of PEI homopolymer, which phase separate, the PEO-g-PEI complexes are water-soluble over the whole range of compositions of the mixture, including the electroneutral stoichiometric complexes. These species apparently represent micelle-like aggregates with a hydrophobic core from the surfactantneutralized polyions and a hydrophilic corona from the ethylene oxide chains. This is a very different morphology compared to the previously described complexes of poly(ethylene oxide)-b-polymethacrylate anions with cationic surfactants, which formed vesicles. The difference in the morphology is attributed to the difference in the copolymer architecture (branched vs linear, graft vs block copolymer, lengths of chain segments). The unique self-assembly behavior, the simplicity of the preparation, and the wide variety of available surfactant components make these systems promising in addressing various theoretical and practical problems, particularly, in pharmaceutics.
Introduction Polymer-surfactant complexes formed between polyions and oppositely charged ionic surfactants are a subject of intensive investigations.1-3 The salt bonds between the ionic units of the polyion and the surfactant headgroups and hydrophobic interactions of the surfactant aliphatic radicals cooperatively stabilize such complexes. Polymer surfactant complexes are characterized by welldefined composition and molecular masses and therefore are considered as a special class of polymer compounds.3 The solution behavior of these complexes strongly depends on their composition, i.e., on the polymer unit to surfactant molecule ratio. Nonstoichiometric complexes containing an excess of one of the components are generally soluble in water. Stoichiometric complexes that contain equivalent amounts of the charged polyion units and surfactant counterions are electroneutral and water-insoluble. A novel family of polymer-surfactant complexes formed by block copolymers containing ionic and nonionic watersoluble segments (block ionomers) and surfactants of opposite charge has recently been reported.4 In the block ionomer complexes the surfactant molecules are bound to the oppositely charged units of the polyion segment like in regular polymer-surfactant complexes formed by * Corresponding author. Fax: (402) 559-9543. E-mail: akabanov@ mail.unmc.edu. † University of Nebraska Medical Center. ‡ McGill University. § Moscow State University. (1) Goddard, E. D. Colloid Surf. 1986, 19, 255. (2) Goddard, E. D.; Ananthapadmanabhan, K. P. Interactions of Surfactants with Polymers and Proteins; CRC Press: Boca Raton, FL, 1993. (3) Ibragimova, Z. Kh.; Kasaikin, V. A.; Zezin, A. B.; Kabanov, V. A. Polym. Sci. USSR 1986, 28, 826 (translated from Vysokomol. Soedin. 1986, A28, 1640). (4) Bronich, T. K.; Kabanov, A. V.; Kabanov, V. A.; Yu, K.; Eisenberg, A. Macromolecules 1997, 30, 3519.
homopolymers. However, the solubility behavior of the block ionomer complexes is quite different because of the effect of the nonionic segment. Particularly, the soluble stoichiometric complexes of poly(ethylene oxide)-b-polymethacrylate anions (PEO-b-PMA) and various singletail cationic surfactants were described.4,5 The selfassembly behavior of block ionomer complexes is unique for the polymer-surfactant complexes. It has been shown that the complexes formed by PEO-b-PMA anions spontaneously arrange into small vesicles with a wall formed by the surfactant-neutralized polyion surrounded by the hydrophilic ethylene oxide shell.5 Such vesicles are very stable and efficiently encapsulate and retain hydrophilic molecules in the internal aqueous volume. The complexes formed between the cationic graft copolymer of poly(ethylene oxide) and poly(ethyleneimine) (PEO-g-PEI) and alkyl sulfate surfactants were studied, and the results are reported in this paper. These complexes are water-soluble over the whole range of compositions including electroneutral complexes. However, they have a different morphology compared to previously described block ionomer complexes of PEOb-PMA with cationic surfactants. The PEO-g-PEI complexes represent micelle-like aggregates with a core from surfactant-neutralized polyions and a corona from ethylene oxide chains. The observed difference in the morphology is attributed to the difference in the copolymer architecture. Experimental Section Materials. PEO-g-PEI copolymer was synthesized by conjugation of poly(ethylene oxide) (PEO), Mn ≈ 8000, with randomly branched polyethyleneimine (PEI), Mw ≈ 2000, following the (5) Kabanov, A.; Bronich, T.; Kabanov, V.; Yu, K.; Eisenberg, A. Polym. Prepr. 1997, 38, 648.
S0743-7463(98)00530-7 CCC: $15.00 © 1998 American Chemical Society Published on Web 09/19/1998
6102 Langmuir, Vol. 14, No. 21, 1998 previously described method.6 Both polymers used for the synthesis were purchased from Aldrich Co. The molecular weight of PEO-g-PEI is Mw)16 600, as determined by static light scattering. The concentration of the total nitrogen in the PEOg-PEI sample determined by the element analysis was 2.16 µmol/ mg. The data on the molecular weight and concentration of total nitrogen corresponded to ca. 1.8 and 2.4 PEO segments per PEI chain, respectively. This was in reasonable agreement with an average PEO/PEI ratio of 1.7, as determined by NMR.6 The anionic surfactants sodium dodecyl sulfate (SDS), sodium tetradecyl sulfate (TDS), and bis(2-ethylhexyl)sulfosuccinate (AOT) were obtained from Sigma and were used without further purification. Fluorescence Measurements. Steady-state fluorescence spectra were recorded on a Shimadzu RF5000U spectrofluorophotometer between 360 and 420 nm. Pyrene was used as the fluorescent probe (excitation wavelength at 333 nm). The sample solutions were prepared by adding known amounts of pyrene in acetone to empty vials. After acetone evaporation, measured amounts of surfactant solution or copolymer/surfactant mixture were added to the vials. The pyrene concentration in the final solution was 5 × 10-7 M (slightly below the solubility of pyrene in water). The sample solutions were stirred overnight at room temperature. All measurements with AOT and SDS were performed at 25 °C, while TDS-containing samples were studied at 37 °C to maintain the solution transparency. Turbidity Measurements. The turbidity measurements were carried out using a Shimadzu UV160 spectrophotometer at 420 nm after equilibration of the sample solutions for at least 3 min. The data are reported as (100 - T)/100, where T is transmittance (%). ζ-Potential and Sizing Measurements. The electrophoretic mobility (EPM) measurements were performed at 25 °C by using a “ZetaPlus” Zeta Potential Analyzer (Brookhaven Instrument Co.) with a 15 mV solid-state laser operated at a laser wavelength of 635 nm. The ζ-potential of the particles was calculated from the EPM values using the Smoluchowski equation. The effective hydrodynamic diameter was measured by photon correlation spectroscopy using the same instrument equipped with the Multi Angle Option. All solutions were prepared using double-distilled water and were filtered repeatedly through a Millipore membrane with a pore size of 0.22 µM. The sizing measurements were performed at 25 °C at an angle of 90°. Electron Microscopy. The negative staining technique was used for the transmission electron microscopy (TEM) studies. A drop of the sample solution was allowed to settle on a Formvar precoated grid for 1 min. Excess sample was wicked away with filter paper and a drop of 1% uranyl acetate solution was allowed to contact the sample for 1 min. The samples were studied using a Hitachi H-7000 microscope.
Results and Discussion Binding Equilibrium. The interaction between PEOg-PEI and various alkyl sulfate surfactants (SDS, TDS, AOT) was characterized by steady-state fluorescence using pyrene as a probe. Pyrene is one of the few condensed aromatic hydrocarbons, which shows significant fine structure in the monomer fluorescence spectra in solution.7,8 The intensity ratio between the first and third highest energy emission peaks in the pyrene spectrum (known as the I1/I3 ratio) correlates with the polarity of the immediate environment of the pyrene molecule. In aqueous solution, the I1/I3 value is about 1.7-1.9, while in a nonpolar solvent such as hexane, it is about 0.6.8 In a typical surfactant solution below the critical micelle concentration (cmc) the I1/I3 value is the same as that in (6) Vinogradov, S. V.; Bronich, T. K.; Kabanov, A. V. Bioconjugate Chem., in press. (7) Becker, R. S.; Singh, I. S.; Jackson, E. A. J. Chem. Phys. 1963, 38, 2144. (8) Kalyanasundaram, K.; Thomas, J. K. J. Am. Chem. Soc. 1977, 99, 2039.
Bronich et al.
Figure 1. Variation of the I1/I3 ratio for the (1) TDS and (2) TDS/PEO-g-PEI mixture as a function of surfactant concentration. Vertical arrows indicate cmc and cac values. The concentration of PEO-g-PEI was 5 × 10-4 base-mol/L, 25 °C, pH 6.0. Table 1. Micellar Characteristics of Various Anionic Surfactants withouta and in the Presenceb of PEO-g-PEI SDS (M)a
cmc cac (M)b
10-2
1.04 × 2.1 × 10-5
TDS 10-3
2.14 × 2.65 × 10-5
AOT 6.39 × 10-4 2.55 × 10-6
water. When the concentration of surfactant exceeds the cmc, the I1/I3 ratio drops significantly, indicating the incorporation of pyrene into the nonpolar interior of the micelle. The interaction between polyions and oppositely charged surfactants is a cooperative process in which the ionic headgroups of the surfactant bind to the polyion units while the surfactant alkyl tails segregate into a hydrophobic microphase.2 This process is characterized by a “critical association concentration” (cac), indicating the onset of surfactant binding to the polymer. Above the cac pyrene incorporates into the nonpolar microphase formed by the surfactant alkyl groups. The I1/I3 ratio of pyrene in aqueous mixtures of PEO-g-PEI with various anionic surfactants was measured as a function of the surfactant concentration. Figure 1 presents typical I1/I3 ratio dependencies for the TDS and PEO-g-PEI mixtures. The I1/I3 values remained fairly constant or changed only slightly below the cac. Above this concentration the I1/I3 values decreased significantly, reflecting pyrene partitioning between the aqueous and micellar phases once the latter was formed. The dependencies of the I1/I3 ratio on the TDS concentration are also shown in Figure 1 for the polymer free system for comparison. The cac value (2.65 × 10-5 M) is about 2 orders of magnitude lower than the corresponding cmc (2.14 × 10-3 M), suggesting that PEO-g-PEI copolymer promoted the surfactant aggregation. The same trend is also observed with other surfactants studied (Table 1). The cac values determined in the presence of PEO-g-PEI copolymer were practically the same as those determined for the PEI homopolymersurfactant systems (data not shown). This behavior is very similar to that reported for the interaction of the N-alkylpyridinium salts and PEO-b-PMA, as well as for regular polyelectrolyte-surfactant systems.2 The shift in cac to lower concentrations compared to the corresponding cmc is explained by the cooperative stabilization of the surfactant aggregates as a result of interaction between the surfactant and polyion chains.2
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Figure 2. Dependencies of the degree of conversion (θ) in the polyion coupling reactions (0, b) and degree of ionization (R) of polybase samples (9, O) for the following systems: AOT/ PEO-g-PEI (curve 1, b); AOT/PEI (curve 2, 0); PEO-g-PEI (curve 3, O); PEI (curve 4, 9). The pH shift, ∆pH, between the θ-pH and R-pH dependencies is shown for the PEO-g-PEI complex as an example.
The binding equilibrium in the PEO-g-PEI and surfactant mixtures was further studied by the potentiometric titration.9 The interaction between an anionic surfactant (S-) and a polybase represents an ion exchange reaction resulting in the release of the hydroxyl ions in accordance with the following scheme:
(|-N(R)H)n + nS- + nH2O S [|-N(R)H2+S-]n + nOH- (I) where R is the -H or -CH2- group of PEI. The acid titration curves were obtained for the mixtures of the surfactants with (1) PEO-g-PEI and (2) PEI homopolymer. In all cases the total concentration of the surfactant was equal to the concentration of the charged amino groups of the polycation.10 The degrees of conversion, θ, in the ion exchange reactions (I) were determined for each studied surfactant from the original titration curves using the following expression:9
θ ) (ma/V + [OH-] - xKbCo)/Co
(1)
where ma is the number of moles of the added acid, V is the current volume of the reaction system, Kb is the characteristic dissociation constant, and Co is the basemolar concentration of the polybase. Figure 2 presents typical θ-pH curves for AOT/PEOg-PEI (curve 1) and AOT/ PEI mixtures (curve 2). The (9) Kabanov, V. A. Polym. Sci. Russ. 1994, 36, 143 (translated from Vysokomol. Soedin. 1994, 36, 183). (10) The branched poly(ethyleneimine) used in this work contained primary, secondary, and tertiary amino groups. The content of primary amino groups (31%) was determined by the fluorescamine titration method with 1,6-diaminohexane as a standard [De Bernardo, S.; Weigele, M.; Toome, V.; Manhart, K.; Leimgruber, W.; Bohlen, P.; Stein, S.; Udenfriend, S. Arch. Biochem. Biophys. 1974, 163, 390]. It was confirmed also by the 1H NMR data that the ratio of primary, secondary, and tertiary amino groups is 1:1:1. It was determined from potentiometric titration curves that only primary and secondary amino groups (i.e., ca. 60% of the total amount) can be protonated. It appears that the tertiary amino groups do not participate in the ion-exchange reactions with anionic surfactant molecules.
Figure 3. Turbidity in the AOT/PEO-g-PEI (curve 1) and AOT/ PEI (curve 2) systems as a function of the charge ratio in the mixture, Z-/+. Ci ) 2.4 × 10-3 base-mol/L, 25 °C, pH 6.0.
ionization degrees, R, for the PEO-g-PEI and the PEI homopolymer in the absence of the surfactant are also presented in this figure (curves 3 and 4). As is seen from Figure 2, the θ values increase sharply over a narrow interval of pH for both PEO-g-PEI and PEI systems. This demonstrates that the interaction between the anionic surfactant and the polycations has a distinct cooperative character and results in the formation of the complexes. The θ-pH curves observed with PEO-g-PEI (curve 1) and PEI (curve 2) were shifted to higher pH compared to the R-pH curves of the corresponding polybases (curves 3 and 4). The pH difference, ∆pH(R), between θ-pH and R-pH curves at each θ ) R provides a differential measure of the free energy of cooperative stabilization of the complex.9,11 Greater shifts of the θ-pH curves to the alkali pH compared to the corresponding R-pH curves indicates a higher stability of the complex. Comparison of the θ-pH and R-pH curves for the PEI (curves 2 and 4) and PEOg-PEI (curves 1 and 3) suggests that the homopolymer complexes are more stable than those of the copolymer. The difference in behavior of the homopolymer and copolymer complexes is probably attributed, by some steric difficulties, to complex formation on the part of two relatively long PEO chains grafted to the PEI segment in the PEO-g-PEI molecule. The results of the potentiometric titration studies using SDS and TDS (data not shown) were very similar to those described above for the AOT-based systems. Overall, these studies suggest that binding equilibrium in the mixtures of anionic surfactants and cationic graft copolymer was similar to that observed with regular polyelectrolytesurfactant complexes. However, the solution behavior of the studied complexes is quite different. Solubility of PEO-g-PEI Complexes. Figure 3 presents data on the turbidity of the AOT/PEO-g-PEI and AOT/PEI mixtures as a function of the charge ratio in the mixture, Z-/+. The charge ratio is expressed as a ratio of the surfactant concentration, Ct, to the concentration of the charged amino groups of the polycation at a given pH, C i:
Z-/+ ) Ct/Ci
(2)
Since the turbidity measurements were performed at pH 6.0, where the ionization of the PEI chains was practically (11) Kabanov, A. V.; Bronich, T. K.; Kabanov, V. A.; Yu, K.; Eisenberg, A. Macromolecules 1996, 29, 6797.
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Bronich et al. Table 2. Effective Diameters of the Electroneutral Complexes Formed between PEO-g-PEI and Various Anionic Surfactants
Figure 4. ζ-Potential of particles formed in SDS/PEO-g-PEI (0), TDS/PEO-g-PEI (2), and AOT/PEO-g-PEI (b) systems at various Z-/+. Ci ) 2.4 × 10-3 base-mol/L, 25 °C, pH 6.0.
complete, Ci approximates the total amount of ionizable groups in the polycation (i.e. ca. 60% of the total amino groups). As seen from Figure 3, the AOT/PEO-g-PEI mixture is practically transparent or slightly opalescent for all values of Z-/+ (curve 1). In contrast, the AOT/PEI system phase separated (curve 2). The same difference in the solution behavior of the copolymer and homopolymer complexes was observed with the TDS- and SDS-based systems (data not shown): PEO-g-PEI complexes remained soluble, while PEI complexes precipitated. It is known that in the cases of relatively short regular polyions, such as PEI studied in this work (polymerization degree ca. 46), the binding of surfactant always results in formation of insoluble stoichiometric complexes.12,13 When the polyion is in excess, the precipitate of the stoichiometric complex coexists in equilibrium with the free polyion in the solution. At the equal concentration of the surfactant and charged units of the polyion all polyion chains become entrapped in the stoichiometric complex, which remains the only product of the reaction. Therefore, the formation of the soluble complexes of PEO-g-PEI over the whole range of the composition of the mixture is a major difference compared to regular polymer surfactant complexes. ζ-Potential and Size of the Complexes. Soluble complexes of PEO-g-PEI were characterized using the laser microelectrophoresis technique and photon correlation spectroscopy. The ζ-potential of the complex particles is presented in Figure 4 as a function of Z-/+. The increase in the amount of the anionic surfactant added to the block ionomer at 0 < Z-/+ e 1 results in the decrease of ζ, indicating a decrease in the net positive charge of the particles. This provides evidence of the progressive neutralization of the polycation fragments of PEO-g-PEI by the surfactant anions incorporated in the complex. Importantly, at Z-/+ ) 1 ζ-potential values are approximately 0, suggesting that the charges of the PEI segments are neutralized completely. This result is consistent with the assumption that at Z-/+ ) 1 all (12) Gilany, T.; Wolfram, E. J. Colloid Surf. 1981, 3, 181. (13) Kasaikin, V. A.; Efremov, V. A.; Zakharova, Yu. A.; Zezin, A. B.; Kabanov, V. A. Dokl. Chem. (Russia) 1997, 354, 126 (translated from Dokl. Akad. Nauk 1997, 354, 498).
anionic surfactant
SDS
TDS
AOT
Deff, nm
36.4
43.6
42.0
surfactant anions added to the system form salt bonds with the protonated amino groups of the PEO-g-PEI. The particles of the electroneutral complexes are about 40-50 nm in diameter and their size practically does not depend on the length of surfactant alkyl groups (Table 2). Consequent measurements with these samples showed no change in ζ-potential and size of stoichiometric complexes for at least several weeks. Since these systems are quite stable in solution and their sizes are close to those of the block copolymer micelles,14-17 it is reasonable to assume that they represent micelle-like aggregates. It was noted that “much of the block copolymer literature refers to the nonequilibrium block copolymer micelle-like aggregates as micelles in recognition of the structural similarity to equilibrium micellar associates”.18 In the case of PEO-g-PEI and surfactant complexes described in this work, we are dealing with a special class of associates. These associates such as regular polymer-surfactant complexes are in equilibrium with the unbound surfactant in solution (cac), which enhances their similarity to the micelles. Furthermore, we found that the size and ζ-potential of the complex particles does not depend of the way of preparation of the system (either surfactant added to PEO-g-PEI or vice versa). Still until more detailed structure and composition studies are conducted to prove the thermodynamic stability of PEO-g-PEI complexes, we prefer to term them the micelle-like aggregates. Apparently, in such aggregates a hydrophobic core from the surfactant-neutralized PEI segments is surrounded by the hydrophilic corona of PEO chains stabilizing the particles in aqueous media. In comparison, PEO-poly(propylene oxide)-PEO copolymer Pluronic F108 having a molecular weight of ca. 16 000 forms micelles with an average diameter of 35 nm (hydrophobic core diameter, 5 nm; PEO corona thickness, 15 nm).15 When Z-/+ exceeds 1, the ζ-potential becomes negative (Figure 4) and the sizes of the particles slightly increase (data not shown). Still, the systems are practically transparent, and no aggregation is observed over several days. The change in the sign of the ζ-potential at Z-/+ > 1 indicates incorporation of the excess of the anionic surfactant into the complex. Similar behavior was previously described for the complexes of the anionic block copolymer and cationic surfactants.4 It was attributed to the incorporation of the surfactant aliphatic groups into the hydrophobic part of the complexes. It is likely that hydrophobic interactions contribute to the surfactant binding in the case of the PEO-g-PEI systems described in this work. The ζ-potential measurements suggest that the least hydrophobic surfactant, SDS, reveals reduced ability for incorporation in the complex at Z-/+ > 1. This is consistent with the hydrophobic binding of the surfactant excess with the complex species. (14) Wilhelm, M.; Zhao, C.-L.; Wang, Y.; Xu, R.; Winnik, M. A.; Mura, J.-L.; Riess, G.; Groucher, M. D. Macromolecules 1991, 24, 1033. (15) Kabanov, A. V.; Nazarova, I. R.; Astafieva, I. V.; Batrakova, E. V.; Alakhov, V. Yu.; Yaroslavov, A. A.; Kabanov, V. A. Macromolecules 1995, 28, 2303-2314. (16) Khougaz, K.; Astafieva, I.; Eisenberg, A. Macromolecules 1995, 28, 7135. (17) Mortensen, K.; Brown, W.; Almdal, K.; Alami, E.; Jada, A. Langmuir 1997, 13, 3635. (18) Zhang, L.; Eisenberg, A. Science 1995, 268, 1728.
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Figure 6. TEM micrograph of stoichiometric TDS/PEO-g-PEI complex obtained using negative staining (uranyl acetate).
Figure 5. Dependence of ζ-potential of particles formed in TDS/PEO-g-PEI system on pH. Ci ) 2.4 × 10-3 base-mol/L, 25 °C.
One additional possible contribution to the binding of the surfactant excess cannot be excluded on the basis of the available data. That is, the anionic surfactant molecules can also interact with the PEO shell. The association reactions in the systems containing uncharged water-soluble polymers (e.g., PEO, poly(vinylpyrrolidone)) and ionic surfactants have been extensively studied.2,19 It was shown that this phenomenon is much more common for the surfactant anions than for the cations. Therefore, both mechanisms can simultaneously realize with the PEO-g-PEI systems providing for the recharging of the complex particles. The net charge of the particles of the complex can be also changed as a result of pH variation at the constant concentrations of the surfactant and PEO-g-PEI. As is seen in Figure 5, the particles, which are electoneutral at pH 6.0, acquire a negative charge when the pH is increased from 6.0 to 10.0. This is obviously due to the decrease in ionization degree of PEI segments, which is accompanied by a change of the number of salt bonds in the complex between the surfactant and the polycation. The recharging of the stoichiometric complexes at elevated pH has the same nature as the formation of the negatively charged particles at the surfactant excess at pH 6.0. Electron Microscopy Characterization. The morphology of the complexes of PEO-g-PEI and various anionic surfactants was investigated by electron microscopy. The images obtained are very similar for all PEO-g-PEI and surfactant pairs. The complex particles are close to spherical over the whole range of Z-/+, as is seen in typical micrographs presented in Figure 6. Also, in some cases, agglomerates of spheres are observed, which probably form during evaporation of the solvent. This morphology is very similar to that reported for spherical micelles formed by diblock ionomers.17,18 Importantly, the micelle-like morphology of PEO-g-PEI complexes is completely different from that of the complexes formed between cationic surfactants and PEO-b-PMA anions.4 It has been shown that the latter complexes spontaneously arrange in small vesicles with the wall from the surfactant-neutralized (19) Brackman, J. C.; Engeberts, J. B. F. N. Chem. Soc. Rev. 1993, 22, 85. (20) Kenworthy, A.; Simon, S. A.; McIntosh, T. J. Biophys. J. 1995, 68, 1903. (21) Hristova, K.; Kenworthy, A.; McIntosh, T. J. Macromolecules 1995, 28, 7693.
polyion surrounded by the hydrophilic ethylene oxide shell.4,5 The micrographs of PEO-g-PEI complexes did not reveal formation of the vesicles at all. This essential distinction in the self-assembly behavior of PEO-g-PEI and PEO-b-PMA complexes appears to be a result of the different molecular architecture of the copolymers. Indeed, the PEO-g-PEI molecule contains a randomly branched PEI fragment. In contrast, the polyion segment in PEO-b-PMA is linear. Also, the PEO-g-PEI contains two PEO segments grafted to the polycation chain while PEO-b-PMA is a diblock copolymer. It is possible that branching in PEI segment and graft copolymer architecture sterically restrict the formation of the continuous lamella-like structures, which is necessary to form the vesicles. At the same time there might be another reason for the formation of the micelle-like structures instead of vesicles in the PEO-g-PEI system. The PEI segment in PEO-gPEI is considerably shorter (46 units) than the ionic block in PEO-b-PMA (186 units). Consequently, the content of PEO segments counting per one salt bond in the PEOg-PEI complex is significantly higher compared to that in the PEO-b-PMA complex. This obviously results in increased steric repulsion of the PEO chains in the hydrophilic corona, which can be balanced out only by the increase in the curvature of the surface of the hydrophobic core. The highest curvature corresponds to the micellar morphology. The transition from bilayer structure to micelles as a result of the increase in the PEO content was theoretically predicted and experimentally verified for the PEO-grafted lipid suspension.20,21 The range of stability of the spontaneous liposomes in PEO-lipid/lipid/ water mixtures was determined as a function of PEOconjugated lipids and polymer molecular weight.22 It is very likely that this approach can be applied for the block (graft) copolymer-surfactant complexes. Indeed, the content of PEO segment in PEO-g-PEI/surfactant complexes is at least about 43%. In contrast, for the previously studied PEO-b-PMA complexes, this value is about 9-11%. Since the PEO repulsion in PEO-g-PEI/surfactant aggregates is much stronger, the formation of spherical micelles in this system becomes more favorable. Validation of this hypothesis is of considerable interest from both theoretical and experimental points of view. In conclusion, this work strongly suggests that the complexes from graft copolymers and oppositely charged surfactants represent lyophilic colloids that exhibit combined properties of polymer micelles and polyelectrolyte complexes. The opportunities for the control of morphology in these systems appear to be much broader than has (22) Szleifer, I.; Gerasimov, O. V.; Thompson, D. H. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 1032.
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been known so far for polymer-surfactant complexes. Comparison of the results of the current work with our previously reported studies on PEO-b-PMA complexes4,5 indicates that self-assembly in these systems is dependent on the copolymer architecture (branched vs linear, graft vs block copolymer, lengths of chain segments). The detailed study of the effects of the copolymer architectural parameters on the morphology of the complexes with surfactants is underway. The unique self-assembly behavior, the simplicity of the preparation, and the wide variety of available surfactant components make these systems promising in addressing various theoretical and practical problems, particularly, in pharmaceutics, where block copolymers and polyelectrolyte complexes are already intensively investigated as drug and gene delivery systems.23-29 (23) Bader, H.; Ringsdorf, H.; Schmidt, B. Angew. Macromol. Chem. 1984, 123/124, 457.
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Acknowledgment. It is a pleasure to acknowledge the financial support from the Division of Material Sciences of the National Science Foundation (DMR 9502807). We would like also to thank Dr. K. Moore and R. Nessler (Central Microscopy Research Facility, University of Iowa) who carried out the negative staining electron microscopy. LA980530X
(24) Kwon, G. S.; Kataoka, K. Adv. Drug. Delivery Rev. 1995, 16, 295. (25) Behr, J. P. Bioconj. Chem. 1994, 5, 382. (26) Kabanov, A. V.; Kabanov, V. A Bioconjugate Chem. 1995, 6, 7. (27) Kabanov, A. V.; Vinogradov, S. V.; Suzdaltseva, Yu. G.; Alakhov, V. Yu. Bioconj. Chem. 1995, 6, 639. (28) Wolfert, M. A.; Schacht, E. H.; Toncheva, V.; Ulbrich, K.; Nazarova, O.; Seymour, L. W. Human. Gene Ther. 1996, 7, 2123. (29) Kataoka, K.; Togawa, H.; Harada, A.; Yasugi, K.; Matsumoto, T.; Katayose, S. Macromolecules 1996, 29, 8556.
