Complexes of Charged-Neutral Block Copolymers and Surfactants: Process-Dependent Features and Long-Term Stability of Their Aqueous Dispersions.

Aqueous dispersions of charged-neutral block copolymers (poly(acrylamide)-b-poly(acrylate)) complexed with an oppositely charged surfactant (dodecyltrimethylammonium) have been prepared by different approaches: the simple mixing of two solutions (MS approach) containing the block copolymer and surfactant, with their respective simple counterions, and dispersion of a freeze-dried complex salt prepared in the absence of simple counterions (CS approach). The CS particles were investigated under different conditions: dispersion of a CS in salt-free water and dispersion of a CS in a dilute salt solution, the latter condition yielding dispersions with the same composition as the MS process. Additionally, aged dispersions (up to 6 months) and dispersed complexes of the polyacrylate homopolymer and dodecyltrimethylammonium surfactant were evaluated. By employing different characterization techniques, it was seen that dispersions prepared by the MS approach display nanometric spherical particles with disordered cores, and poor colloidal stability, partially caused by the absence of surface charge (ζ-potential close to zero). Oppositely, anisometric particles were formed in CS dispersions and were large enough to sustain micellar cubic cores. The CS particles presented long-time colloidal stability, partially due to a net negative surface charge, but the stability varied with the length of the neutral block composing the corona. Our results demonstrate that all dispersed particles are metastable structures, with physicochemical properties strongly dependent on the preparation procedure, thus making these particles suitable for fundamental studies and potential applications where accurate control of their properties, including size, shape, internal structure, and stability, is desired.

Versatile Diblock Polyampholytes Can Form Two Types of Charged and Internally Structured Core-Shell Particles by Complexation with Cationic or Anionic Surfactants.

We used diblock poly(acrylic acid)-b-poly(2-dimethylamino ethyl methacrylate) (PAA-b-PDMAEMA) polyampholytes to prepare core-shell complexes with ionic surfactants. The dispersions have been characterized by means of small-angle X-ray scattering (SAXS), cryogenic transmission electron microscopy (Cryo-TEM), dynamic light-scattering, and zeta potential methods. Using cationic or anionic surfactants it is possible to produce particles with either positively or negatively charged shells, both having an internal liquid-crystalline core structure. For the different systems, different preparation protocols were found to be successful to produce stable and reproducible particles. The particle morphologies depend on the surfactant used. Complexes with the cationic surfactant hexadecyltrimethylammonium (CTA+) form oblate particles, while complexes with dodecyl sulfate (DS-) form cylindrical rods. In both complexes, the smallest dimension of the core does not exceed twice the block length of the core-forming polymer block. For the particles with CTA+, nonelectrostatic attractive interactions among the PDMAEMA chains in the shells seem to be present, affecting the particle shape. In both types of particles, the surfactant in the core forms rod-like aggregates, arranged in a two-dimensional hexagonal structure with the surfactant rods aligned with the axis of rotational symmetry in the particle. With charged polymer chains in the shell, the aggregates present a striking stability over time, displaying no change in particle size over the time scale investigated (10 months). Nevertheless, the aggregates are highly dynamic in nature, and their shapes and structures can be changed dramatically in dispersion, without intermediate precipitation, by changes in the composition of the medium. Specifically, a transition from aggregates with cationic surfactant to aggregates with anionic surfactant can be achieved.

Molecular Assembly in Block Copolymer-Surfactant Nanoparticle Dispersions: Information on Molecular Exchange and Apparent Solubility from High-Resolution and PFG NMR.

Internally structured block copolymer-surfactant particles are formed when the complex salts of ionic-neutral block copolymers neutralized by surfactant counterions are dispersed in aqueous media. Here, we report the 1H NMR signal intensities and self-diffusion coefficients (D, from pulsed field gradient nuclear magnetic resonance, PFG NMR) of trimethyl alkylammonium surfactant ions and the poly(acrylamide)-block-poly(acrylate) (PAAm-b-PA) polyions forming such particles. The results reveal the presence of an "NMR-invisible" (slowly exchanging) fraction of aggregated surfactant ions in the particle core and an "NMR-visible" fraction consisting of surface surfactant ions in rapid exchange with the surfactant ions dissociated into the aqueous domain. They also confirm that the neutral PAAm blocks are exposed to water at the particle surface, while the PA blocks are buried in the particle core. The self-diffusion of the polyions closely agree with the self-diffusion of a hydrophobic probe molecule solubilized in the particles, showing that essentially all copolymer chains are incorporated in the aggregates. Through centrifugation, we prepared macroscopically phase-separated systems with a phase concentrated in particles separated from a clear dilute phase. D values for the surfactant and block copolymer indicated that the dilute phase contained small aggregates (ca. 5 nm) of surfactant ions and a few anionic-neutral block copolymer chains. Regardless of the overall concentration of the sample, the fraction of block copolymer found in the dilute phase was nearly constant. This indicates that the dilute fraction represented a tail of small particles created by the dispersion process rather than a true thermodynamic solubility of the complex salts.

Co-elution phenomena in polymer mixtures studied by asymmetric flow field-flow fractionation.

Most polymers generally have complex characteristics. Analysis and understanding of these characteristics is crucial as they, for instance, influence functionality. Separation and analysis of samples of polymers, biopolymers in particular, is challenging since they often display broad distributions in size, structure and molar mass (M) and/or a tendency to form aggregates. Only few analytical techniques are suitable for the task. AF4-MALS-dRI is highly suited for the task, but the analysis can nevertheless be especially challenging for heterogeneous mixtures of polymers that exhibit wide size distributions or aggregation. For such systems, systematic and thorough method development is clearly a requirement. This is the purpose of the present work, where we approach the problem of heterogeneous polymer samples systematically by analyzing mixtures of two different polymers which are also characterized individually. An often observed phenomenon in AF4 of samples with a high polydispersity is a downturn in M vs. elution time, especially common at high retention. This result is often dismissed as an artifact attributed to various errors in detection and data processing. In this work, we utilize AF4-MALS-dRI to separate and analyze binary mixtures of the well-known polysaccharides pullulan and glycogen, or pullulan and poly(ethylene oxide), respectively, in solution. The results show that an observed downturn - or even an upturn - in M can be a correct result, caused by inherent properties of the analyzed polymers.

Isotherms and Kinetics of Water Vapor Sorption/Desorption for Surface Films of Polyion-Surfactant Ion Complex Salts.

Thin films of "complex salts" (CS = ionic surfactants with polymeric counterions) have recently been shown to respond to humidity changes in ambient air by changing their liquid crystalline structure. We here report isotherms and kinetics of water sorption/desorption for ∼10-100 µm films of alkyltrimethylammonium polyacrylate CS, measured in a dynamic gravimetric vapor sorption instrument over a 0-95% relative humidity (RH) range. The sorption per ion pair was similar to that observed for common ionomers. A kinetic model for the water exchange is presented, assuming that the "external" transport between the vapor reservoir and the film surface is rate-determining. The model predicts that the water content, after a small stepwise change of the reservoir RH, should vary exponentially with time, with a time constant proportional to both the slope of the sorption isotherm and the film thickness. These predictions were confirmed for our films over large RH ranges, and the external mass transfer coefficient in our setup was calculated from the experimental data. Expressions derived for the Biot number (ratio of characteristic times for internal and external water transport) for the considered limiting case strongly indicate that external water transport should quite generally affect, or even dominate, the measured kinetics for similarly thin hydrated films.

Time- and Space-Resolved SAXS Experiments Inform on Phase Transition Kinetics in Hydrated, Liquid-Crystalline Films of Polyion-Surfactant Ion "Complex Salts".

Detailed time- and space-resolved SAXS experiments show the variation with hydration of liquid crystalline structures in ethanol-cast 5-80 µm thick films of polyion-surfactant ion "complex salts" (CS). The CS were dodecyl- (C12) or hexadecyl- (C16) trimethylammonium surfactants with polyacrylate (DP 25 or 6000) counter-polyions. The experiments were carried out on vertical films in humid air above a movable water bath, so that gradients of hydration were generated, which could rapidly be altered. Scans over different positions along a film, kept fixed relative to the bath, showed that the surfactant aggregates of the various liquid-crystalline CS structures grow in cross-sectional area with decreasing hydration. This behavior is attributed to the low water content. Studies of films undergoing rapid dehydration, made possible by the original experimental setup, gave strong evidence that some of the investigated systems remain kinetically trapped for minutes in a nonequilibrium Pm3n micellar cubic phase before switching to the equilibrium P6mm 2D hexagonal phase. Both the length of the polyion and the length of the surfactant hydrocarbon "tail" affect the kinetics of the phase transition. The slowness of the cubic-to-hexagonal structural transition is attributed to the fact that it requires major rearrangements of the polyions and surfactant ions relative to each other. By contrast, other structure changes, such as between the hexagonal and rectangular phases, were observed to occur much more rapidly.

Depletion controlled surface deposition of uncharged colloidal spheres from stable bulk dispersions.

The competition between surface adsorption and bulk aggregation was investigated for silica colloids dispersed in cyclohexane in contact with hydrophobized silica substrates. Central to this study is that the colloids and surfaces have the same material and surface properties. Colloid-colloid and colloid-surface interactions were controlled by addition of polymers providing depletion interaction. Bulk instability was determined by turbidity and viscosity measurements and surface adsorption by ellipsometry measurements. At increasing polymer concentration, strong surface adsorption occurred at polymer concentrations below that required for bulk phase separation. Complementary Monte Carlo simulations with the use of a new weak depletion theory support quantitatively the experimental observation of the existence of an interval of interaction strength at which aggregation in bulk is negligible while surface adsorption is substantial.

Selective co-deposition of anionic silica particles at hydrophobic surfaces from formulations of oppositely charged polymers and surfactants.

The surface-selective surface deposition of anionic hydrophilic silica particles from aqueous polymer-surfactant formulations was investigated by in-situ null-ellipsometry. The formulations, with or without silica particles, contained anionic sodium dodecylsulfate (SDS) and a cationic polymer, cationic hydroxyethyl cellulose (cat-HEC) or a copolymer of acrylamide and methacrylamidopropyl trimethylammonium chloride (AAm/MAPTAC). Surface deposition from the formulations onto model surfaces of either anionic hydrophilic, or hydrophobized, silica was induced by controlled dilution of the formulations into the coacervation region, and was monitored with time by ellipsometry. The dilution simulated a rinsing process in a typical application. In all cases a steady-state surface layer remained after extensive dilution. An enhanced deposition from the silica-containing formulations was found on the hydrophobized silica surface, indicating a substantial co-deposition of silica particles. Much less co-deposition, or none at all, was found on hydrophilic silica. The opposite trend, enhanced co-deposition on hydrophilic silica, was previously found in similar experiments with hydrophobic silicone oil droplets as co-deposants (Clauzel et al., 2011). The amphiphilic cationic polymers evidently favor a "mismatched" co-deposition of anionic particles to hydrophobic surfaces, or vice versa. The findings suggest a strategy for surface-specific delivery of particles to surfaces.

Addition of n-Alcohols Induces a Variety of Liquid-Crystalline Structures in Surfactant-Rich Cores of Dispersed Block Copolymer/Surfactant Nanoparticles.

Poly(acrylamide)-b-complex salts made from a symmetric poly(acrylate-b-acrylamide) block copolymer, where the acrylate charges are neutralized by cationic surfactant counterions, form kinetically stable aqueous dispersions of hierarchical aggregates with a liquid-crystalline complex salt core and a diffuse hydrated shell. By the addition of suitable amounts of long-chain alcohols, such as octanol or decanol, the structure of the internal phase can be varied, producing micellar cubic, hexagonal, lamellar, or reverse hexagonal liquid-crystalline phases. In addition, a disordered reverse micellar phase forms at the highest content of octanol. These core structures are the same as those previously obtained for macroscopic homopolymer poly(acrylate) complex salt/water/n-alcohol systems at the corresponding compositions. The poly(acrylamide)-b-complex salt dispersions are kinetically stable for several weeks, with their colloidal properties and internal structures remaining unchanged. The methodology described here establishes an easy and robust protocol for the preparation of colloidal nanoparticles with variable but controlled internal structures.

Water-Insoluble Surface Coatings of Polyion-Surfactant Ion Complex Salts Respond to Additives in a Surrounding Aqueous Solution.

Hydrated, but water-insoluble, "complex salts" (CS) composed of alkyltrimethylammonium surfactant ions with polyacrylate counterions are known to exhibit a rich phase behavior in bulk mixtures with water and have recently been shown to act as water-responsive surface coatings. Here it is shown, by SAXS measurements, that surface coatings of CS also respond to various added solutes in a surrounding aqueous solution, by altering their liquid crystalline structure. The obtained results provide new information on the phase behavior of CS in contact with water and aqueous solutions. Solutes such as acids, salts, excess ionic surfactant, or water-soluble polymers act on the CS by altering the polyion charge density, screening the electrostatic interaction, changing the curvature of the surfactant aggregate, or increasing the osmotic pressuring in the surrounding solution, all of which may result in a phase transition in the film. In water, all studied CS surface coatings had a micellar cubic structure, which could change to 2D hexagonal, HCP, or disordered micellar structure, depending on the identity of the CS and the identity and concentration of the added solute. For some systems, even dissolved CO2 from the ambient air was sufficient to induce a structural change in the film. Especially the films containing the long polyions remained intact even for large concentrations of solutes in the contacting solutions, and extensive washing in water resulted, in most cases, in films with the "original" structure found in water.

Water-responsive internally structured polymer-surfactant films on solid surfaces.

Water-insoluble films of oppositely charged polyion-surfactant ion "complex salts" (CS) are readily cast on solid surfaces from ethanolic solutions. The methodology introduces new possibilities to study and utilize more or less hydrated CS. Direct SAXS measurements show that the surface films are water-responsive and change their liquid crystalline structure in response to changes in the water activity of the environment. In addition to the classical micellar cubic and hexagonal phases, a rectangular ribbon phase and a hexagonal close-packed structure have now been detected for CS composed of cationic alkyltrimethylammonium surfactants with polyacrylate counterions. Added cosurfactants, decanol or the nonionic surfactant C12E5, yield additional lamellar and bicontinuous cubic structures. Images of the surfaces by optical and atomic force microscopy show that the films cover the surfaces well but have a more or less irregular surface topology, including "craters" of sizes ranging from a few to hundreds of micrometers. The results indicate possibilities to create a wealth of water-responsive structured CS films on solid surfaces.

Effects of added surfactant on swelling and molecular transport in drug-loaded tablets based on hydrophobically modified poly(acrylic acid).

A combination of NMR chemical shift imaging and self-diffusion experiments is shown to give a detailed molecular picture of the events that occur when tablets of hydrophobically modified poly(acrylic acid) loaded with a drug (griseofulvin) swell in water in the presence or absence of surfactant (sodium octylbenzenesulfonate). The hydrophobic substituents on the polymer bind and trap the surfactant molecules in mixed micelles, leading to a slow effective surfactant transport that occurs via a small fraction of individually dissolved surfactant molecules in the water domain. Because of the efficient binding of surfactant, the penetrating water is found to diffuse past the penetrating surfactant into the polymer matrix, pushing the surfactant front outward as the matrix swells. The added surfactant has little effect on the transport of drug because both undissolved solid drug and surfactant-solubilized drug function as reservoirs that essentially follow the polymer as it swells. However, the added surfactant nevertheless has a strong indirect effect on the release of griseofulvin, through the effect of the surfactant on the solubility and erosion of the polymer matrix. The surfactant effectively solubilizes the hydrophobically modified polymer, making it fully miscible with water, leading to a more pronounced swelling and a slower erosion of the polymer matrix.

Soluble aggregates in aqueous solutions of polyion-surfactant ion complex salts and a nonionic surfactant.

Water-soluble aggregates based on two polyion-surfactant ion "complex salts", consisting of hexadecyltrimethylammonium (C16TA(+)) and polyacrylate (PA(-)) with either 25 or 6000 repeating units, with added nonionic surfactant octaethylene glycol monododecyl ether (C12E8) have been investigated. A previous phase study has shown that added C12E5 or C12E8 can solubilize complex salts in aqueous systems, and that increasing the poly(ethylene oxide) chain length of the nonionic surfactant and/or decreasing the polyion length favors dissolution. In this work we report on dynamic light scattering, NMR diffusometry, small-angle X-ray scattering, and isothermal titration calorimetry measurements performed to characterize the solubilized composite aggregates in dilute aqueous solution in terms of size and stoichiometry. It was found that mixed aggregates of polyacrylate, C16TA(+) ions, and C12E8, with almost constant stoichiometry, coexist with free micelles of C12E8 at all investigated mixing ratios. The length of the polyion only weakly affects the stoichiometry of the mixed aggregates while strongly affecting their size and water solubility.

Quantifying the release of lactose from polymer matrix tablets with an amperometric biosensor utilizing cellobiose dehydrogenase.

The release of lactose (hydrophilic) from polymer tablets made with hydrophobically modified poly(acrylic acid) (HMPAA) have been studied and compared to the release of ibuprofen, a hydrophobic active substance. Lactose is one of the most used excipients for tablets, but lactose release has not been widely studied. One reason could be a lack of good analytical tools. A novel biosensor with cellobiose dehydrogenase (CDH) was used to detect the lactose release, which has a polydiallyldimethylammonium chloride (PDADMAC) layer that increases the response. A sample treatment using polyethylenimine (PEI) was developed to eliminate possible denaturants. The developed methodology provided a good approach to detect and quantify the released lactose. The release was studied with or without the presence of a model amphiphilic substance, sodium dodecyl sulphate (SDS), in the release medium. Ibuprofen showed very different release rates in the different media, which was attributed to hydrophobic interactions between the drug, the HMPAA and the SDS in the release medium. The release of hydrophilic lactose, which did not associate to any of the other components, was rapid and showed only minor differences. The new methodology provides a useful tool to further evaluate tablet formulations by a relatively simple set of experiments.

Using NMR chemical shift imaging to monitor swelling and molecular transport in drug-loaded tablets of hydrophobically modified poly(acrylic acid): methodology and effects of polymer (in)solubility.

A new technique has been developed using NMR chemical shift imaging (CSI) to monitor water penetration and molecular transport in initially dry polymer tablets that also contain small low-molecular weight compounds to be released from the tablets. Concentration profiles of components contained in the swelling tablets could be extracted via the intensities and chemical shift changes of peaks corresponding to protons of the components. The studied tablets contained hydrophobically modified poly(acrylic acid) (HMPAA) as the polymer component and griseofulvin and ethanol as hydrophobic and hydrophilic, respectively, low-molecular weight model compounds. The water solubility of HMPAA could be altered by titration with NaOH. In the pure acid form, HMPAA tablets only underwent a finite swelling until the maximum water content of the polymer-rich phase, as confirmed by independent phase studies, had been reached. By contrast, after partial neutralization with NaOH, the polyacid became fully miscible with water. The solubility of the polymer affected the water penetration, the polymer release, and the releases of both ethanol and griseofulvin. The detailed NMR CSI concentration profiles obtained highlighted the clear differences in the disintegration/dissolution/release behavior for the two types of tablet and provided insights into their molecular origin. The study illustrates the potential of the NMR CSI technique to give information of importance for the development of pharmaceutical tablets and, more broadly, for the general understanding of any operation that involves the immersion and ultimate disintegration of a dry polymer matrix in a solvent.

Polyelectrolyte adsorption on solid surfaces: theoretical predictions and experimental measurements.

This work utilizes a combination of theory and experiments to explore the adsorption of two different cationic polyelectrolytes onto oppositely charged silica surfaces at pH 9. Both polymers, poly(diallyldimethylammonium chloride), PDADMAC, and poly(4-vinyl N-methylpyridinium iodide), PVNP, are highly charged and highly soluble in water. Another important aspect is that a silica surface carries a relatively high surface charge density at this pH level. This means that we have specifically chosen to investigate adsorption under conditions where electrostatics can be expected to dominate the interactions. Of specific focus in this work is the response of the adsorption to the addition of simple salt (i.e., a process where electrostatics is gradually screened out). Theoretical predictions from a recently developed correlation-corrected classical density functional theory for polyelectrolytes are evaluated by direct quantitative comparisons with corresponding experimental data, as obtained by ellipsometry measurements. We find that, at low concentrations of simple salt, the adsorption increases with ionic strength, reaching a maximum at intermediate levels (about 200 mM). The adsorption then drops but retains a finite level even at very high salt concentrations, indicating the presence of nonelectrostatic contributions to the adsorption. In the theoretical treatment, the strength of this relatively modest but otherwise largely unknown nonelectrostatic surface affinity was estimated by matching predicted and experimental slopes of adsorption curves at high ionic strength. Given these estimates for the nonelectrostatic part, experimental adsorption data are essentially captured with quantitative accuracy by the classical density functional theory.

Understanding and exploiting the phase behavior of mixtures of oppositely charged polymers and surfactants in water.

Complexes of oppositely charged polymers and surfactants (OCPS) in water come in many varieties, including liquid-crystalline materials, soluble complexes, structured nanoparticles, and water-insoluble surface layers. The range of available structures and properties increases even further with the addition of other amphiphilic substances that may enter, or even dissolve, the complexes, depending on the nature of the additive. Simple operations may change the properties of OCPS systems dramatically. For instance, dilution with water can induce a phase separation in an initially stable OCPS solution. More complicated processes, involving chemical reactions, can be used to either create or disintegrate OCPS particles or surface layers. The richness of their properties has made OCPS mixtures ubiquitous in everyday household products, such as shampoos and laundry detergents, and also attractive ingredients in the design of new types of responsive particles, surfaces, and delivery agents of potential use in future applications. A challenge for the rational design of an OCPS system is, however, to obtain a good fundamental understanding of how to select molecular shapes and sizes and how to tune the hydrophobic and electrostatic interactions such that the desired properties are obtained. Recent studies of OCPS phase equilibria, using a strategy where the minimum number of components is always used to address a particular question, have brought out general rules and trends that can be used for such a rational design. Those fundamental studies are reviewed here, together with more application-oriented studies where fundamental learning has been put to use.

Surfactants modify the release from tablets made of hydrophobically modified poly (acrylic acid).

Many novel pharmaceutically active substances are characterized by a high hydrophobicity and a low water solubility, which present challenges for their delivery as drugs. Tablets made from cross-linked hydrophobically modified poly (acrylic acid) (CLHMPAA), commercially available as Pemulen™, have previously shown promising abilities to control the release of hydrophobic model substances. This study further investigates the possibility to use CLHMPAA in tablet formulations using ibuprofen as a model substance. Furthermore, surfactants were added to the dissolution medium in order to simulate the presence of bile salts in the intestine. The release of ibuprofen is strongly affected by the presence of surfactant and/or buffer in the dissolution medium, which affect both the behaviour of CLHMPAA and the swelling of the gel layer that surrounds the disintegrating tablets. Two mechanisms of tablet disintegration were observed under shear, namely conventional dissolution of a soluble tablet matrix and erosion of swollen insoluble gel particles from the tablet. The effects of surfactant in the surrounding medium can be circumvented by addition of surfactant to the tablet. With added surfactant, tablets that may be insusceptible to the differences in bile salt level between fasted or fed states have been produced, thus addressing a central problem in controlled delivery of hydrophobic drugs. In other words CLHMPAA is a potential candidate to be used in tablet formulations for controlled release with poorly soluble drugs.

Phase behavior and rheological properties of DNA-cationic polysaccharide mixtures.

Associative aqueous mixtures over a range of concentrations of double- (ds) or single- (ss) stranded DNA with dilute or semidilute solutions of two cationic derivatives of hydroxyethyl cellulose (cat-HEC and cat-HMHEC,(1) the latter carrying grafted hydrophobic groups), were studied. The phase behavior showed an interesting asymmetry: Phase separation occurred immediately when small (sub-stoichiometric) amounts of cationic polyelectrolyte were added to the DNA solution, but redissolution into a single cat-(HM)HEC/DNA/H(2)O phase occurred already with a modest charge excess of the cationic polyelectrolyte, at a charge ratio approximately independent of the overall polyelectrolyte concentration. Cat-HEC/dsDNA/H(2)O and cat-HEC/ssDNA/H(2)O systems presented a considerable difference in the extension of the phase separation region. The one-phase samples with excess cationic polyelectrolyte were studied by rheology. The presence of DNA strengthened the viscoelastic behavior of the solutions of the cationic polyelectrolytes, reflected in an increase in storage modulus and viscosity. Differences in phase behavior and rheology were observed, particularly between systems containing cat-HEC or cat-HMHEC, but also between dsDNA and ssDNA. Thus, these systems allow for the preparation of DNA formulations with widely variable rheology and water uptake.

Polyion-surfactant ion complex salts formed by a random anionic copolyacid at different molar ratios of cationic surfactant: phase behavior with water and n-alcohols.

The presence of acid groups with different pK(a) values in the anionic copolymer poly(4-styrene sulfonic acid-co-maleic acid), P(SS-Ma), allowed the preparation of complex salts with a variable fraction of anionic groups neutralized by cationic surfactant in the copolymer via controlled titration with hexadecyltrimethylammonium hydroxide, C(16)TAOH. Two new complex salts were selected for detailed phase studies, C(16)TA(2)P(SS-Ma) and C(16)TA(3)P(SS-Ma), where both had 100% charged styrene sulfonate groups, but the fraction of charged carboxylate groups on the polyion was 50% or 100%, respectively. These complex salts thus contained both hydrophobic (styrene sulfonate) and hydrophilic (carboxylate) charged groups, and the ratio between the two could be altered by titration. These features were found to have consequences for the phase behavior in water and in ternary mixtures with water and n-alcohols for the two complex salts, which differed compared to complex salts containing homo- or copolyions with only carboxylate or styrene sulfonate charged groups. For both complex salts, binary mixtures with water produced, in the dilute region, two isotropic phases in equilibrium, the bottom (concentrated) one displaying increasing viscosity with increasing concentration. For the complex salt C(16)TA(2)P(SS-Ma), there was evidence of micellar growth to form anisometric aggregates at high concentrations. For the C(16)TA(3)P(SS-Ma) complex salt, this was not observed, and the isotropic phase was followed by a narrow region of cubic phase. In both cases, concentrations above ca. 60 wt % produced a hexagonal phase. For ternary mixtures with n-alcohols, the general trend was that a short-chain alcohol such as n-butanol acted as a cosolvent dissolving the aggregates, whereas with n-decanol, a cosurfactant effect was observed, inducing the formation of lamellar phases. Visual inspection (also between crossed polarizers), small angle X-ray scattering (SAXS) and diffusion nuclear magnetic resonance (NMR) were used in these studies.