Synthesis and Characterization of a Thermoresponsive Copolymer with an LCST-UCST-like Behavior and Exhibiting Crystallization.

In this work, the diblock copolymer methoxy-poly(ethylene glycol)-block-poly(ε-caprolactone) (MPEG-b-PCL) was synthesized with a block composition that allows this polymer in aqueous media to possess both an upper critical solution temperature (UCST) and a lower critical solution temperature (LCST) over a limited temperature interval. The value of the UCST, associated with crystallization of the PCL-block, depended on heating (H) or cooling (C) of the sample and was found to be CPUCSTH = 32 °C and CPUCSTC = 23 °C, respectively. The LCST was not affected by the heating or cooling scans; assumed a value of 52 °C (CPLCSTH = CPLCSTC). At intermediate temperatures (e.g., 45 °C), dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM) showed that the solution consisted of a large population of spherical core-shell particles and some self-assembled rodlike objects. At low temperatures (below 32 °C), differential scanning calorimetry (DSC) and wide-angle X-ray scattering (WAXS) in combination with SAXS disclosed the formation of crystals with a cylindrical core-shell structure. Cryo-TEM supported a thread-like appearance of the self-assembled polymer chains. At temperatures above 52 °C, incipient phase separation took place and large aggregation complexes of amorphous morphology were formed. This work provides insight into the intricate interplay between UCST and LCST and the type of structures formed at these conditions in aqueous solutions of MPEG-b-PCL diblock copolymers.

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.

Interactions in Aqueous Mixtures of Cationic Hydroxyethyl Cellulose and Different Anionic Bile Salts.

It is known that the reduction of blood cholesterol can be accomplished through foods containing a large number of dietary fibers; this process is partially related to the binding of bile salt to fibers. To gain new insights into the interactions between dietary fibers and bile salts, this study investigates the interactions between cationic hydroxyethyl cellulose (catHEC) and sodium deoxycholate (NaDC) or sodium cholate (NaC), which have a similar structure. Turbidity measurements reveal strong interactions between catHEC and NaDC, and under some conditions, macroscopic phase separation occurs. In contrast, the interactions with NaC are weak. At a catHEC concentration of 2 wt %, incipient phase separation is approached at concentrations of NaC and NaDC of 32.5 and 19.3 mM, respectively. The rheological results show strong interactions and a prominent viscosification effect for the catHEC/NaDC system but only moderate interactions for the catHEC/NaC system. Both cryogenic transmission electron microscopy and small-angle X-ray scattering results display fundamental structural differences between the two systems, which may explain the stronger interactions in the presence of NaDC. The surmise is that the extended structures formed in the presence of NaDC can easily form connections and entanglements in the network.

Noncovalent Bile Acid Oligomers as Facial Amphiphilic Antimicrobials.

New antimicrobial agents are needed to address the ever-growing risk of bacterial resistance, particularly for methicillin- and vancomycin-resistant Staphylococcus aureus (S. aureus). Here, we report a class of bile acid oligomers as facial amphiphilic antimicrobials, which are noncovalently fabricated by cholic acid (CA) and deoxycholic acid (DCA) with polyamines (e.g., diamines, diethylenetriamine, spermidine, and spermine). The antibacterial activities of these bile acid oligomers (CA/polyamines and DCA/polyamines) against S. aureus become stronger with increasing the amine group numbers of polyamines without obviously enhanced cytotoxicity and skin irritation. DCA/spermine, entirely composed of natural products, exhibits the best antibacterial activity but the lowest cytotoxicity and the weakest skin irritation. All CA/polyamines and DCA/polyamines form well-ordered ribbon-like aggregates, collecting numerous facial amphiphilic structures to significantly enhance the interactions with bacterial membranes. In particular, the biogenic polyamines with more than two amine groups provide extra positively charged sites, hence facilitating the binding of bile acid oligomers to the negatively charged outer membrane of the bacteria via electrostatic interaction. This in turn promotes more oligomeric bile acid units that can be inserted into the membrane through hydrophobic interaction between bile acids and lipid domains. The noncovalently constructed and separable amphiphilic antimicrobials can avoid the long-term coexistence of microorganisms and antibacterial molecules in different acting modes. Therefore, the noncovalent bile acid oligomers, especially those with higher oligomerization degrees, can be a potential approach to effectively enhance antibacterial activity, improve environmental friendliness, and reduce bacterial drug resistance.

Bioderived, chiral and stable 1-dimensional light-responsive nanostructures: Interconversion between tubules and twisted ribbons.

HYPOTHESIS: Self-assembling molecular structures responding to light stimulus are appealing for applications as sensing and drug delivery. Supramolecular nanotubes have a relevant potential in nanotechnology as they can be used to encapsulate different loads like drugs, biological macromolecules, and nanomaterials. In addition, they are suitable elements for novel supracolloidal materials. Structural responses of supramolecular nanotubes to non-invasive stimuli are very much desired to enable controlled release of the encapsulated guests and to provide these recently developed new materials with an external trigger. Here, we describe the formation of well-defined, single wall tubules that interconvert into twisted ribbons upon UV-light exposure in aqueous environment. The structures are provided by self-assembly of an azobenzene substituted cholic acid, a biological surfactant belonging to the family of bile acids. The azobenzene group allows for the light responsiveness of the molecular packing. Concurrently the steroidal moieties assure both chiral features and extensive hydrophobic interactions for time and temperature resistant aggregates. EXPERIMENTS: The molecular packing interconversion was followed by circular dichroism. Microscopy, small angle X-ray scattering and light scattering measurements demonstrated the drastic morphological variation upon irradiation. A model of the molecular arrangement within the tubular walls was suggested based on the circular dichroism spectra simulation. FINDINGS: Innovatively, the molecular design reported in our work allows for encoding in the same light responsive system multiple desirable features (e.g. bio-origin, temperature resistance and chirality of the aggregates). Such combination of properties, never reported before for a single molecule, might be relevant for the realization of robust, stimuli-responsive bio-vectors.

Condensed Supramolecular Helices: The Twisted Sisters of DNA.

Condensation of DNA helices into hexagonally packed bundles and toroids represents an intriguing example of functional organization of biological macromolecules at the nanoscale. The condensation models are based on the unique polyelectrolyte features of DNA, however here we could reproduce a DNA-like condensation with supramolecular helices of small chiral molecules, thereby demonstrating that it is a more general phenomenon. We show that the bile salt sodium deoxycholate can form supramolecular helices upon interaction with oppositely charged polyelectrolytes of homopolymer or block copolymers. At higher order, a controlled hexagonal packing of the helices into DNA-like bundles and toroids could be accomplished. The results disclose unknown similarities between covalent and supramolecular non-covalent helical polyelectrolytes, which inspire visionary ideas of constructing supramolecular versions of biological macromolecules. As drug nanocarriers the polymer-bile salt superstructures would get advantage of a complex chirality at molecular and supramolecular levels, whose effect on the nanocarrier assisted drug efficiency is a still unexplored fascinating issue.

Tuning lipid structure by bile salts: Hexosomes for topical administration of catechin.

The delivery of bio-active molecules through the skin is challenging given the complex structure of its outer layer, the stratum corneum. Here we explore the possibility to encapsulate natural compounds into nanocarriers containing permeation enhancers that can affect the fluidity of the stratum corneum lipids. This approach is expected to facilitate dermal or transdermal release. For this purpose, the application of bile salts, which are natural surfactants involved in vivo in lipid digestion, was exploited. Bile salts were added to lipid liquid crystalline nanoparticles (NPs) made of monoolein for antioxidant topical delivery. Monoolein self-assembly behaviour in water was affected by the presence of bile salts molecules, giving a transition from a bicontinuous cubic to unilamellar vesicles dispersion. By adding oleic acid (OA), the change of curvature in the system led to a reverse hexagonal phase. The morphology, structure and size of the nanocarriers was investigated before the nanoparticles were loaded with catechin, a natural antioxidant occurring in plants and food. The encapsulation did not affect significantly the formulation phase behaviour. The formulation loaded with bile salts and catechin was thereafter tested in vitro on the skin from new-born pig. The results for two different lipid formulations without bile salts were compared under the same experimental conditions and with the same antioxidant. The formulation with bile salts showed the best performance, allowing a superior permeation of catechin in the different skin layers in comparison with formulations without bile salt.

Surface-modified nanoerythrosomes for potential optical imaging diagnostics.

Nanoerythrosomes (NERs), vesicle-like nanoparticles derived from red blood cells, represent a new and interesting vector for therapeutic molecules and imaging probes, mainly thanks to their high stability and excellent biocompatibility. Aiming to present a proof-of-concept of the use of NERs as diagnostic tools for in vitro/in vivo imaging purposes, we report here several functionalization routes to decorate the surfaces of NERs derived from bovine blood with two different fluorophores: 7-amino-4-methylcumarin and dibenzocyclooctinecyanine5.5. Notably, the fluorophores were cross-linked to the NERs surface with glutaraldehyde and, in the case of dibenzocyclooctinecyanine5.5, also using a click-chemistry route, termed strain-promoted azide-alkyne cycloaddition. The physicochemical characterization highlighted the high stability of the NERs derivatives in physiological conditions. Furthermore, the loading efficiency of the fluorophores on the NERs surface was evaluated using both UV-Vis spectroscopy and fluorescence microscopy.

Supracolloidal Atomium.

Nature suggests that complex materials result from a hierarchical organization of matter at different length scales. At the nano- and micrometer scale, macromolecules and supramolecular aggregates spontaneously assemble into supracolloidal structures whose complexity is given by the coexistence of various colloidal entities and the specific interactions between them. Here, we demonstrate how such control can be implemented by engineering specially customized bile salt derivative-based supramolecular tubules that exhibit a highly specific interaction with polymeric microgel spheres at their extremities thanks to their scroll-like structure. This design allows for hierarchical supracolloidal self-assembly of microgels and supramolecular scrolls into a regular framework of "nodes" and "linkers". The supramolecular assembly into scrolls can be triggered by pH and temperature, thereby providing the whole supracolloidal system with interesting stimuli-responsive properties. A colloidal smart assembly is embodied with features of center-linker frameworks as those found in molecular metal-organic frameworks and in structures engineered at human scale, masterfully represented by the Atomium in Bruxelles.

Poloxamer/sodium cholate co-formulation for micellar encapsulation of doxorubicin with high efficiency for intracellular delivery: An in-vitro bioavailability study.

HYPOTHESIS: Doxorubicin hydrochloride (DX) is widely used as a chemotherapeutic agent, though its severe side-effects limit its clinical use. A way to overcome these limitations is to increase DX latency through encapsulation in suitable carriers. However, DX has a high solubility in water, hindering encapsulation. The formulation of DX with sodium cholate (NaC) will reduce aqueous solubility through charge neutralization and hydrophobic interactions thus facilitating DX encapsulation into poloxamer (F127) micelles, increasing drug latency. EXPERIMENTS: DX/NaC/PEO-PPO-PEO triblock copolymer (F127) formulations with high DX content (DX-PMs) have been prepared and characterized by scattering techniques, transmission electron microscopy and fluorescence spectroscopy. Cell proliferation has been evaluated after DX-PMs uptake in three cell lines (A549, Hela, 4T1). Cell uptake of DX has been studied by means of confocal laser scanning microscopy and flow cytometry. FINDINGS: DX-PMs formulations result in small and stable pluronic micelles, with the drug located in the apolar core of the polymeric micelles. Cell proliferation assays show a delayed cell toxicity for the encapsulated DX compared with the free drug. Data show a good correlation between cytotoxic response and slow DX delivery to nuclei. DX-PMs offer the means to restrict DX delivery to the cell interior in a highly stable and biocompatible formulation, suitable for cancer therapy.

C-12 vs C-3 substituted bile salts: An example of the effects of substituent position and orientation on the self-assembly of steroid surfactant isomers.

Biomolecule derivatives are transversally used in nanotechnology. Deciphering their aggregation behavior is a crucial issue for the rational design of functional materials. To this end, it is necessary to build libraries of selectively functionalized analogues and infer general rules. In this work we enrich the highly applicative oriented collection of steroid derivatives, by reporting a rare example of C-12 selectively modified bile salt. While nature often exploits such position to encode functions, it is unusual and not trivial to prepare similar analogues in the laboratory. The introduction of a tert-butyl phenyl residue at C-12 provided a molecule with a self-assembly that remarkably switched from rigid pole-like structures to twisted ribbons at a biologically relevant critical temperature (∼25 °C). The system was characterized by microscopy and spectroscopy techniques and compared with the C-3 functionalized analogue. The twisted ribbons generate samples with a gel texture and a viscoelastic response. The parallel analysis of the two systems suggested that the observed thermoresponsive self-assemblies occur at similar critical temperatures and are probably dictated by the nature of the substituent, but involve aggregates with different structures depending on position and orientation of the substituent. This study highlights the self-assembly properties of two appealing thermoresponsive systems. Moreover, it adds fundamental insights hereto missing in the investigations of the relation between self-assembly and structure of synthetic steroids, which are valuable for the rational design of steroidal amphiphiles.

Block copolymers as bile salt sequestrants: intriguing structures formed in a mixture of an oppositely charged amphiphilic block copolymer and bile salt.

To study the formation and characterize the structure of mixed complexes of oppositely charged block copolymers and surfactants are of great significance for practical applications, e.g., in drug carrier formulations that are based on electrostatically assisted assembly. In this context, biocompatible block copolymers and biosurfactants (like bile salts) are particularly interesting. In this work, we report on the co-assembly in dilute aqueous solution between a cationic poly(N-isopropyl acryl amide) (PNIPAM) diblock copolymer and the oppositely charged bile salt surfactant sodium deoxycholate at ambient temperature. The cryogenic transmission electron microscopy (cryo-TEM) experiments revealed the co-existence of two types of co-assembled complexes of radically different morphology and inner structure. They are formed mainly as a result of the electrostatic attraction between the positively charged copolymer blocks and bile salt anions and highlight the potential of using linear amphiphilic block copolymers as bile salt sequestrants in the treatment of bile acid malabsorption and hypercholesterolemia. The first complex of globular morphology has a coacervate core of deoxycholate anions and charged copolymer blocks surrounded by a PNIPAM corona. The second complex has an intriguing tape-like supramolecular morphology of several micrometer in length that is striped in the direction of the long axis. A model is presented in which the stretched cationic blocks of several block copolymers interact electrostatically with the bile salt molecules that are associated to form a zipper-like structure. The tape is covered on both sides by the PNIPAM chains that stabilize the overall complex in solution. In addition to cryo-TEM, the mixed system was investigated in a range of molar charge fractions at a constant copolymer concentration by static light scattering, small angle X-ray scattering, and electrophoretic mobility measurements.

A fluorescence study of the loading and time stability of doxorubicin in sodium cholate/PEO-PPO-PEO triblock copolymer mixed micelles.

HYPOTHESIS: Doxorubicin hydrochloride (DX) is one of the most powerful anticancer agents though its clinical use is impaired by severe undesired side effects. DX encapsulation in nanocarrier systems has been introduced as a mean to reduce its toxicity. Micelles of the nonionic triblock copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) (PEO-PPO-PEO), are very promising carrier systems. The positive charge of DX confines the drug to the hydrophilic corona region of the micelles. The use of mixed micelles of PEO-PPO-PEO copolymers and a negatively charged bile salt should favour the solubilization of DX in the apolar core region of the micelles. EXPERIMENTS: We studied the DX uptake in the micellar systems formed by sodium cholate (NaC) and the PEO100PPO65PEO100 (F127) copolymer, prepared with different mole ratios (MR = nNaC/nF127) in the range 0 ÷ 1. The systems were characterized by small angle X-ray scattering (SAXS) and dynamic light scattering (DLS); DX encapsulation was followed by steady-state and time-resolved fluorescence spectroscopy. FINDINGS: The successful solubilization of DX in the host micellar systems did not affect their structure, as evidenced by both SAXS and DLS data. In the presence of NaC, DX experiences a more apolar environment as indicated by its characteristic fluorescent behaviour. The almost complete uptake of the drug occurred shortly after the sample preparation; however, time resolved fluorescence revealed a slow partition of DX between corona and core regions of the micelles. DX degradation in the mixed micellar systems was markedly reduced relative to aqueous DX solutions.

Twisted nanoribbons from a RGD-bearing cholic acid derivative.

In light of the biomedical interest for self-assembling amphiphiles bearing the tripeptide Arg-Gly-Gly (RGD), a cholic acid derivative was synthesized by introducing an aromatic moiety on the steroidal skeleton and the RGD sequence on the carboxylic function of its chain 17-24, thus forming a peptide amphiphile with the unconventional rigid amphiphilic structure of bile salts. In aqueous solution, the compound self-assembled into long twisted ribbons characterized by a very low degree of polydispersity in terms of width (≈25nm), thickness (≈4.5nm) and pitch (≈145nm). It was proposed that in the ribbon the molecules are arranged in a bilayer structure with the aromatic moieties in the interior, strongly involved in the intermolecular interaction, whereas the RGD residues are located at the bilayer-water interface. The nanostructure is significantly different from those generally provided by RGD-containing amphiphiles with the conventional peptide-tail structure, for which fibers with a circular cross-section were observed, and successfully tested as scaffolds for tissue regeneration. From previous work on the use of this kind of nanostructures, it is known that features like morphology, rigidity, epitope spacing and periodicity are important factors that dramatically affect cell adhesion and signaling. Within this context, the reported results demonstrate that bile salt-based peptide surfactants are promising building blocks in the preparation of non-trivial RGD-decorated nanoaggregates with well-defined morphologies and epitope distributions.

On the formation of inclusion complexes at the solid/liquid interface of anchored temperature-responsive PNIPAAM diblock copolymers with γ-cyclodextrin.

The thermal responsive behavior of adsorbed layers of diblock copolymers of poly(N-isopropylacrylamide) (PNIPAAM) and poly((3-acrylamidopropyl)trimethylammonium chloride) (PAMPTMA(+)) with γ-cyclodextrin (γ-CD) at the solid/liquid interface has been investigated using three in situ techniques: null ellipsometry, quartz-crystal microbalance with dissipation monitoring, and neutron reflectometry. The measurements provided information about the adsorbed amounts, the layer thickness, hydration and viscoelastic properties, and the interfacial structure and composition. The copolymers adsorb to silica with the cationic PAMPTMA(+) blocks sitting as anchors in a flat conformation and the PNIPAAM chains extending into the solution. The copolymer system alone exhibits reversible collapse above the lower critical solution temperature of PNIPAAM. The addition of γ-CD to pre-adsorbed copolymer layers results in a highly extended conformation as well as some loss of copolymer from the surface, which we discuss in terms of the formation of surface-invoked lateral steric repulsion of formed inclusion complexes.

Effects of Bile Salt Sodium Glycodeoxycholate on the Self-Assembly of PEO-PPO-PEO Triblock Copolymer P123 in Aqueous Solution.

A comprehensive experimental study on the interaction between the PEO-PPO-PEO block copolymer P123 (EO20PO68EO20) and the anionic bile salt sodium glycodeoxycholate (NaGDC) in water has been performed. The work was aimed at investigating the suitability of using P123 as bile salt sequestrant beside the fundamental aspects of PEO-PPO-PEO block copolymer-bile salt interactions. Various experimental techniques including dynamic and static light scattering, small-angle X-ray scattering, and differential scanning calorimetry (DSC) were employed in combination with electrophoretic mobility measurements. The system was investigated at a constant P123 concentration of 1.74 mM and with varying bile salt concentrations up to approximately 250 mM NaGDC (or a molar ratio n(NaGDC)/n(P123) = 144). In the mixed P123-NaGDC solutions, the endothermic process related to the self-assembly of P123 was observed to gradually decrease in enthalpy and shift to higher temperatures upon progressive addition of NaGDC. To explain this effect, the formation of NaGDC micelles carrying partly dehydrated P123 unimers was proposed and translated into a stoichiometric model, which was able to fit the experimental DSC data. In the mixtures at low molar ratios, NaGDC monomers associated with the P123 micelle forming a charged "P123 micelle-NaGDC" complex with a dehydrated PPO core. These complexes disintegrated upon increasing NaGDC concentration to form small "NaGDC-P123" complexes visualized as bile salt micelles including one or a few P123 copolymer chains.

Tailoring supramolecular nanotubes by bile salt based surfactant mixtures.

An approach for tailoring self-assembled tubular structures is described. By controlling the relative composition of a two-component surfactant mixture comprising the natural bile salt lithocholate and its bolamphiphilic derivative, it was possible to finely tune the nanotube cross-section of the mixed tubular aggregates that self-associated spontaneously in aqueous solution at pH 12. The diameter was found to vary up to 50% when the stoichiometric ratio of the two bile salts was changed. The tuning of supramolecular nanochannels with such remarkable precision is of significant interest for technological applications of these materials.

Cubosome formulations stabilized by a dansyl-conjugated block copolymer for possible nanomedicine applications.

We present here an innovative, fluorescent, monoolein-based cubosome dispersion. Rather than embedded within the monoolein palisade, the fluorescent imaging agent, namely dansyl, was conjugated to the terminal ethylene oxide moieties of the block copolymer Pluronic F108. We discuss the physicochemical and photophysical properties of this fluorescent Pluronic and of a cubosome formulation stabilized by a mixture of dansyl-conjugated and non-conjugated Pluronic, also including an anticancer drug (quercetin). Furthermore, we performed biocompatibility tests against HeLa cells to assess internalization and cytotoxicity features of this nanoparticles aqueous dispersion. Cryo-TEM, SAXS, and DLS analysis, proved the bicontinuous cubic inner nanostructure and the morphology of this fluorescent cubosome dispersion, while photophysical measurements and biocompatibility results basically validate their potential use for theranostic nanomedicine applications.

Interactions of small dendrimers with sodium dodecyl sulfate at the air-water interface.

We have determined how the bulk behavior of mixtures of small cationic poly(amidoamine) dendrimers (generation 2, PAMAM-G2) and sodium dodecyl sulfate (SDS) affects the structure and composition of the adsorbed layers at the air-water interface. The aim is to reveal how the size of a well-defined hyperbranched polyelectrolyte affects the interfacial and bulk solution behavior of mixtures with oppositely charged surfactants, when the size of the polyelectrolyte approaches that of the surfactant. A combination of electrophoretic mobility, UV-vis spectroscopy, dynamic light scattering, and small-angle X-ray scattering measurements have been employed to characterize the interactions in the bulk solution. PAMAM-G2 associates strongly with SDS in the bulk, forming large aggregates where the size and the charge depend on the bulk composition. We show that kinetically trapped aggregates can be formed at compositions outside the equilibrium two-phase region, and the positively charged aggregates are larger than the negative ones. Surface tensiometry, neutron reflectometry, and ellipsometry have been used to reveal the properties of the interfacial layers. The interfacial structures formed depend strongly on the bulk composition: structured layers are present for samples inside the two-phase region, whereas intact nanostructured aggregates adsorb for samples just outside the two-phase region. The interfacial behavior of PAMAM-G2/SDS mixtures is compared with that of small amines or multivalent ions and oppositely charged surfactants. The implications of aggregate adsorption, dissociation, and spreading processes are discussed as well as the potential of small dendrimers for applications involving the delivery of functional molecules to interfaces.

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.