Mixed Block Copolymer Solutions: Self-Assembly and Interactions

This thesis incorporates studies on the aqueous systems of two types of thermoresponsive amphiphilic block copolymers; a series of nonionic triblock copolymers comprising blocks of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) denoted as PEO-PPO-PEO block copolymers, and a series of ionic diblock copolymers consisting of one charged block and one block of poly(N-isopropylacrylamide) (PNIPAAM). Various techniques, such as dynamic and static light scattering (DLS and SLS), small angle X-ray and neutron scattering (SAXS and SANS), high sensitivity differential scanning calorimetry (HSDSC), turbidimetry, electrophoretic mobility measurements, and two-dimensional proton NMR nuclear Overhauser effect spectroscopy (2D 1H NMR NOESY), were applied to study these block copolymer systems.In the first part of the thesis, the influence of a bile salt, sodium glycodeoxycholate (NaGDC), on the self-assembly of the three PEO-PPO-PEO block copolymers, P123, F127 and P65, was studied. Apart from the fundamental physio-chemical point of view, the overall aim of this study was to investigate if these types of block copolymers are potential candidates to be used as bile acid sequestrants in the treatment of bile acid diarrhea and hypercholesterolemia diseases. It was found that the NaGDC does influence the self-assembly of these block copolymers in a similar way, but not as effectively as the classical ionic surfactants. At low bile salt concentrations and above the CMT of the pure aqueous solutions of these polymers, charged PEO-PPO-PEO micelle-NaGDC complexes are formed. The SAXS results indicated that the NaGDC molecules are located mostly in the corona of the block copolymer micelles, close to the core-corona interface. However, at higher bile salt concentrations, during their disintegration, these complexes are generally in coexistence with small NaGDC-rich complexes. The latter complexes resemble the NaGDC micelles in terms of size and structure. Among the three studied block copolymers, P65 micelles are the easiest to disintegrate by NaGDC. The F127 and P123 micelles show almost the same stability when interacting with NaGDC.The second part in this thesis primarily describes the investigation of the effects of temperature, salt, PNIPAAM block length, and polymer concentration on the association behavior of a series of the three diblock copolymers, poly(N-isopropylacrylamide)-b-poly((3-acrylamidopropyl) trimethylammonium chloride) (PNIPAAMn-b-PAMPTMA(+)20), where n=24, 48, and 65. It was shown that the cloud point (CP) of the polymer solutions decreases upon an increase in PNIPAAM block length, and polymer and salt concentrations. At temperatures below CP of the polymer solutions, unimers and micellar/intermicellar clusters coexist. However, at temperatures above the CP, the dominant particles in the solutions are the large aggregates, which generally retain stable sizes in the presence of salt and upon increasing the temperature.Finally the aqueous mixed solutions of PNIPAAM26-b-PAMPTMA(+)15 and poly(N-isopropylacrylamide)-b-poly(sodium 2-acrylamido-2-methyl-1-propanesulfonate) (PNIPAAM27-b-PAMPS(−)15) with an equimolar charge condition were studied. Mixed micelles were observed at total concentrations ranging from 0.2 to 0.5 wt % in all studied temperatures (10– 30 oC). The mixed micelles have a cylindrical structure, and are formed via an attractive electrostatic interaction between the oppositely charged PAMPTMA(+) and PAMPS(−) blocks. However, in addition to the charged blocks interaction, there is evidence of interaction between the PNIPAAM and the charged blocks, as demonstrated by 2D 1H NMR NOESY experiments

Complexes of PEO-PPO-PEO triblock copolymer P123 and bile salt sodium glycodeoxycholate in aqueous solution : A small angle X-ray and neutron scattering investigation

Small angle X-ray (SAXS) and neutron scattering techniques were combined to study mixed complexes formed between micelles of the nonionic amphiphilic PEO-PPO-PEO copolymer (P123) and the anionic bile salt (NaGDC) in aqueous solution. The purpose was to investigate the structural parameters of the charged complexes, such as size and internal structure, as well as their interparticle interactions in aqueous solution. The overall aim of this work was to gain understanding of how thermoresponsive PEO-PPO-PEO block copolymers interact with bile salts in order to make predictions as to whether they can be put forward as a new class of bile salt sequestrants in the treatment of bile-salt related diseases. The system was investigated at a constant P123 concentration of 1.74 mM and bile salt concentrations were varied up to a molar ratio [Formula presented] (MR) = 5.7. It was found that the NaGDC molecules preferentially associated to the PEO corona of the P123 micelle and due to their amphiphilic nature, close to the core/corona interface. Because of this association the micelles became charged causing their reciprocal interparticle repulsions in solution to increase. In parallel, the association caused a decrease in the core radius accompanied by dehydration, which in turn led to a decrease in total radius of the “P123 micelle-NaGDC” complexes. To elucidate the effect of the interactions on their diffusive motion, an interaction model based on a spherical particle with a hard-core interaction shell was employed using the fitted SAXS data. At higher molar ratios, the interparticle interaction was increasingly screened because of nonadsorbed bile salt in the surrounding solution. Meanwhile, a further decrease in total radial size of the P123 micelle-NaGDC complexes occurred due to a decrease in the aggregation number of P123 as the bile salt finally disintegrated the complexes. However, the micelles were found to be more stable and less prone to disintegration in D2O. This investigation demonstrated the importance of using small angle scattering techniques for studying intermolecular interactions in order to gain understanding of how natural surfactants influence the aggregation behavior of amphiphilic polymers

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 nNaGDC/nP123 = 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

Nanoparticles with a Bicontinuous Cubic Internal Structure Formed by Cationic and Non-ionic Surfactants and an Anionic Polyelectrolyte.

Nanoparticles with an internal structure have been prepared by dispersing under dilute conditions poly(acrylic acid) with a polymerization degree n = 6000 (PAA6000) together with a cationic surfactant hexadecyltrimethylammonium hydroxide (C16TAOH) and the non-ionic surfactant penta(ethylene glycol) monododecyl ether (C12E5) in water. The nanoparticles are formed at different mixing ratios in the corresponding two-phase regions (liquid crystalline phase/dilute isotropic phase) of the C16TAPA6000 complex salt/ C12E5/water ternary phase diagram. The particles consist of polyacrylate PA6000 − polyions, C16TA+ surfactant ions, and C12E5. Their internal ordering was identified by small-angle Xray scattering (SAXS) to be either bicontinuous cubic with the Ia3d crystallographic space group or normal hexagonal depending upon the amount of C12E5. The bicontinuous cubic phase, to our knowledge never observed before in polyelectrolyte−surfactant particle systems, was inferred by SAXS experiments. The data also showed that this structure is thermoresponsive in a reversible manner. The bicontinuous cubic space group transforms from Ia3d to Im3m as the temperature decreases from 25 to 15 °C. According to dynamic light scattering and electrophoretic mobility measurements, the particles have a well-defined size (apparent hydrodynamic radii RH in the range of 88−140 nm) and carry a positive net charge. The size of the nanoparticles is stable up to 1 month. The faceted nanoparticles are visualized by cryogenic transmission electron microscopy that also reveals their coexistence with thread-like C12E5 micelles

Interaction between Bile Salt Sodium Glycodeoxycholate and PEO-PPO-PEO Triblock Copolymers in Aqueous Solution

The interactions of the anionic bile salt NaGDC with three triblock copolymers based on poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), denoted P65, P123 and F127, were investigated using high-sensitive differential scanning calorimetry (DSC), turbidimetry, dynamic and static light scattering and small angle X-ray scattering (SAXS). P65 and P123 had the same hydrophilic PEO block lengths, whereas F127 and P123 had the same hydrophobic PPO block length. In water, the block copolymers self-assembled and formed spherical micelles at a critical micelle temperature, which depended on both the PPO/PEO composition ratio and the molecular weight of the copolymer. The mixed systems were studied at a constant P65, P123 or F127 concentration (i.e., 1.0 wt% or 5.0 wt%) with varying nNaGDC/npolymer molar ratio (MR) from 0 to 12. The DSC measurements presented endothermic enthalpy values (correlated to the amount of PPO that dehydrates in the aggregation process) that were suppressed at high MR. At 50 °C, the NaGDC molecules associated to the PPO core – PEO corona interface of the copolymer micelle forming a negatively charged block copolymer micelle–NaGDC complex. The complexes began to disintegrate upon NaGDC addition. Their resistance to disruption followed the stability order as inferred from the CMT values. At 20 °C, the unassociated block copolymer chains interacted with the NaGDC micelles and formed small NaGDC-rich complexes with a radius of ∼2 nm as determined by SAXS

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

Mixed micelles of oppositely charged poly(N-isopropylacrylamide) diblock copolymers

Mixed micelle formation between two oppositely charged diblock copolymers that have a common thermosensitive nonionic block of poly(N-isopropylacrylamide) (PNIPAAM) has been studied. The block copolymer mixed solutions were investigated under equimolar charge conditions as a function of both temperature and total polymer concentrations by turbidimetry, differential scanning calorimetry, two-dimensional proton nuclear magnetic nuclear Overhauser effect spectroscopy (2D 1H NMR NOESY), dynamic light scattering, and small angle X-ray scattering measurements. Well-defined and electroneutral cylindrical micelles were formed with a radius and a length of about 3 nm and 35 nm, respectively. In the micelles, the charged blocks built up a core, which was surrounded by a corona of PNIPAAM chains. The 2D 1H NMR NOESY experiments showed that a minor block mixing occurred between the core blocks and the PNIPAAM blocks. By approaching the lower critical solution temperature of PNIPAAM, the PNIPAAM chains collapsed, which induced aggregation of the micelles

On the self-assembly of a tryptophan labeled deoxycholic acid

Self-assembly of peptides and bile acids has been widely investigated because of their biological role and their potential as a tool for the preparation of nanostructured biomaterials. We herein report both the synthesis and the self-association behavior of a compound that combines the aggregation properties of bile acid- and amino acid-based molecules. The derivative has been prepared by introducing a L-tryptophan residue into the C-3 position of the deoxycholic acid skeleton and resulted in an amphoteric fluorescent labeled bile acid that shows a pH-dependent self-assembly. Under alkaline conditions it assembles into 28 nm diameter tubules, thus showing a completely different behavior compared to the precursor bile acid, which forms micelles under similar conditions. Upon heating the tubules break and turn into micelles, leading to an increase in the exposure to water of the tryptophan residue. On the other hand, in acidic solutions it aggregates into elongated micelles that further self-assemble forming a gel network, when an electrolyte is added