Paschalis Alexandridis

Poly(ethylene oxide)-poly(propylene oxide )-poly (ethylene oxide) block copolymer surfactants in aqueous solutions and at interfaces: thermodynamics, structure, dynamics, and modeling

Abstract The association properties of poly(ethylene oxide)-block-poly(propyleneoxide)-block-poly(ethylene oxide) (PEOPPOPEO) copolymers (commercially available as Poloxamers and Pluronics) in aqueous solutions, and the adsorption of these copolymers at interfaces are reviewed. At low temperatures and/or concentrations the PEOPPOPEO copolymers exist in solution as individual coils (unimers). Thermodynamically stable micelles are formed with increasing copolymer concentration and/or solution temperature, as revealed by surface tension, light scattering, and dye solubilization experiments. The unimer-to-micelle transition is not sharp, but spans a concentration decade or 10 K. The critical micellization concentration (CMC) and temperature (CMT) decrease with an increase in the copolymer PPO content or molecular weight. The dependence of CMC on temperature, together with differential scanning calorimetry experiments, indicates that the micellization process of PEOPPOPEO copolymers in water is endothermic and driven by a decrease in the polarity of ethylene oxide (EO) and propylene oxide (PO) segments as the temperature increases, and by the entropy gain in water when unimers aggregate to form micelles (hydrophobic effect). The free energy and enthalpy of micellization can be correlated to the total number of EO and PO segments in the copolymer and its molecular weight. The micelles have hydrodynamic radii of approximately 10 nm and aggregation numbers in the order of 50. The aggregation number is thought to be independent of the copolymer concentration and to increase with temperature. Phenomenological and mean-field lattice models for the formation of micelles can describe qualitatively the trends observed experimentally. In addition, the lattice models can provide information on the distribution of the EO and PO segments in the micelle. The PEOPPOPEO copolymers adsorb on both airwater and solidwater interfaces; the PPO block is located at the interface while the PEO block extends into the solution, when copolymers are adsorbed at hydrophobic interfaces. Gels are formed by certain PEOPPOPEO block copolymers at high concentrations, with the micelles remaining apparently intact in the form of a “crystal”. The gelation onset temperature and the thermal stability range of the gel increase with increasing PEO block length. A comparison of PEOPPO copolymers with PEOPBO and PEO PS block copolymers and CiEj surfactants is made, and selected applications of PEOPPOPEO block copolymer solutions (such as solubilization of organics, protection of microorganisms, and biomedical uses of micelles and gels) are presented.

Poly(ethylene oxide)/poly(propylene oxide) block copolymer surfactants

Block copolymers consisting of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) can self-assemble in water and water/oil mixtures (where water is a selective solvent for PEO and oil a selective solvent for PPO) to form thermodynamically stable spherical micelles as well as an array of lyotropic liquid crystalline mesophases of varying morphology. Significant advances have been made over the past year on the identification of different morphologies, the delineation of the composition-temperature ranges where they occur, and the structural characterization of the morphologies using primarily small angle scattering techniques. Important new findings on the copolymer micellization in water as affected by cosolutes, and on the time-dependency of the surface activity have also been reported.

Amphiphilic copolymers and their applications

Recently there have been advances in the fundamental understanding of the self-organization of amphiphilic copolymers at interfaces and in solutions and in the presence of solvents. Research has recently extended to amphiphilic polymers that have been used a great deal in the past, but have not been studied in any great detail. Also, applications that take advantage of self-assembly have also advanced and this has resulted in products with novel macroscopic properties which are used by the medical, pharmaceutical, cosmetic, agricultural and other industries.

Non-invasive multimodal functional imaging of the intestine with frozen micellar naphthalocyanines

Overview There is a need for safer and improved methods for non-invasive imaging of the gastrointestinal tract. Modalities based on X-ray radiation, magnetic resonance and ultrasound suffer from limitations with respect to safety, accessibility or lack of adequate contrast. Functional intestinal imaging of dynamic gut processes has not been practical using existing approaches. Here, we report the development of a family of nanoparticles that can withstand the harsh conditions of the stomach and intestine, avoid systemic absorption, and give rise to good optical contrast for photoacoustic imaging. The hydrophobicity of naphthalocyanine dyes was exploited to generate purified ~20 nm frozen micelles, which we call nanonaps, with tunable and large near-infrared absorption values (>1000). Unlike conventional chromophores, nanonaps exhibited non-shifting spectra at ultrahigh optical densities and, following oral administration in mice, passed safely through the gastrointestinal tract. Non-invasive, non-ionizing photoacoustic techniques were used to visualize nanonap intestinal distribution with low background and remarkable resolution with 0.5 cm depth, and enabled real-time intestinal functional imaging with ultrasound co-registration. Positron emission tomography following seamless nanonap radiolabelling allowed complementary whole body imaging.

Physicochemical aspects of drug delivery and release from polymer-based colloids

Abstract Recent advances in the preparation/loading, surface properties, and applications of polymer-based colloidal drug delivery and release systems, such as block copolymer micelles, polymer nano- and microparticles, polymer-modified liposomes, and chemical and physical hydrogels are presented. Drug release from polymer-based systems is affected by the drug–polymer interactions as well as the polymer microstructure and dissociation/erosion properties. Surface modification with poly(ethylene oxide) has become common in improving the biocompatibility and biodistribution of drug delivery carriers. Site-specific drug delivery can be achieved by polymer-based colloidal drug carriers when ligands of targeting information are attached on the carrier surface or when a phase transition is induced by an external stimulus. While significant progress in being made, many challenges remain in preserving the biological activity and attaining the desired drug release properties, especially for protein and DNA drugs.

Polyhedral Oligomeric Silsesquioxane (POSS)-Containing Polymer Nanocomposites

Hybrid materials with superior structural and functional properties can be obtained by incorporating nanofillers into polymer matrices. Polyhedral oligomeric silsesquioxane (POSS) nanoparticles have attracted much attention recently due to their nanometer size, the ease of which these particles can be incorporated into polymeric materials and the unique capability to reinforce polymers. We review here the state of POSS-containing polymer nanocomposites. We discuss the influence of the incorporation of POSS into polymer matrices via chemical cross-linking or physical blending on the structure of nanocomposites, as affected by surface functional groups, and the POSS concentration.

Interaction of poloxamer block copolymers with cosolvents and surfactants

Abstract The interactions of poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (PEO–PPO–PEO) block copolymers (Poloxamers) with cosolvents and surfactants are addressed here. Ternary isothermal (25°C) systems of Pluronic F127 (Poloxamer 407) in the presence of water and polar water-miscible solvents (glycerol, propylene glycol or ethanol), a partially water-miscible solvent (glycerol triacetate), a non-ionic surfactant (tetraethylene glycol monooctyl ether, C8(EO)4), an anionic surfactant (sodium dodecyl sulfate, SDS), and a cationic surfactant (cetyltrimethyl ammonium bromide, CTAB) have been investigated by phase behavior studies and small angle x-ray scattering (SAXS). A number of regions with different lyotropic liquid crystalline structure have been identified in each ternary Poloxamer–water–cosolvent/surfactant system. For a given Poloxamer, the composition range over which a given self-assembled structure is stable varies according to the cosolvent/surfactant type (and properties). The effects that the different cosolvents or surfactants exhibit on the Poloxamer phase behavior are interpreted in terms of the preference of the cosolvent/surfactant molecules to locate in different domains of the PEO–PPO–PEO block copolymer self-assembly. Organic solvents, depending on their relative polarities, locate preferably in the PEO-rich or the PPO-rich domains of the microstructure. Some solvents (e.g. ethanol and glycerol triacetate) may show amphiphilic behavior and act as cosurfactants by preferably locating at the interface between the PEO-rich and the PPO-rich domains. The location of the solvents in the block copolymer assemblies is established by an analysis of the trends in the structure lattice spacing (obtained from SAXS) and the interfacial area per block copolymer molecule.

Modification of the lyotropic liquid crystalline microstructure of amphiphilic block copolymers in the presence of cosolvents

This article reviews the results of recent investigations on the macroscopic (phase behavior) and microscopic (microstructure) aspects of the role of cosolvents on the self-assembly of amphiphilic copolymers. A comprehensive account of the systematic studies performed in ternary isothermal systems consisting of a representative poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymer (Pluronic P105, EO37PO58EO37), water and a polar cosolvent (such as glycerol, propylene glycol or ethanol) is presented. The effect of cosolvents on the copolymer phase behavior is quantified in terms of the highest cosolvent/water ratio able to maintain the liquid crystalline structures. The effect of cosolvents on the microstructure of the lyotropic liquid crystals is quantified in terms of the degree of relative swelling per cosolvent content per copolymer content, a parameter that characterizes the given cosolvent and copolymer. The set of correlations on the cosolvent effects on the phase behavior or microstructure to the cosolvent physicochemical characteristics (such as octanol/water partition coefficient or solubility parameter) have led to the development of a hypothesis that accounts for the cosolvent effects on the self-assembly of PEO-PPO-PEO block copolymers and can be used to predict them. The rich structural diversity and the potential for a precise an convenient modification of the lyotropic liquid crystalline microstructure of the PEO-PPO-PEO block copolymers is discussed in comparison to the phase behavior of the low-molecular nonionic surfactants.

Utilizing temperature-sensitive association of Pluronic F-127 with lipid bilayers to control liposome^cell adhesion

The temperature sensitive properties of Pluronic F-127 (MW approximately 12600, PEO(98)-PPO(67)-PEO(98)), a block co-polymer or poloxamer, was used to control liposome-cell adhesion. When associated with liposomes, the PEO moiety of the block co-polymer is expected to inhibit liposome-cell adhesion. Liposomes were made using egg phosphatidylcholine and different mole% of Pluronic F-127. Size measurement of the liposomes at different temperatures, in the presence and absence of Pluronic F-127, shows significant reduction in the size of multilamellar vesicles, at higher temperatures, by the Pluronic molecules. Negative stain electron microscopy study showed the presence of individual molecules and micelles of Pluronic, respectively at temperatures below and above the critical micellar temperature (CMT). Measurement of the surface associated Pluronics indicated that they associated with liposomes when the sample was heated above the Pluronic CMT, and dissociated from liposomes when cooled below the CMT. Attachment of the Pluronic containing liposomes to CHO cells was inhibited at temperatures above the CMT, but not at temperatures below CMT, indicating that temperature-sensitive control of liposome-cell adhesion is achieved.

Solution Structure of Human von Willebrand Factor Studied Using Small Angle Neutron Scattering

von Willebrand factor (VWF) binding to platelets under high fluid shear is an important step regulating atherothrombosis. We applied light and small angle neutron scattering to study the solution structure of human VWF multimers and protomer. Results suggest that these proteins resemble prolate ellipsoids with radius of gyration (Rg) of ∼75 and ∼30 nm for multimer and protomer, respectively. The ellipsoid dimensions/radii are 175 × 28 nm for multimers and 70 × 9.1 nm for protomers. Substructural repeat domains are evident within multimeric VWF that are indicative of elements of the protomer quarternary structure (16 nm) and individual functional domains (4.5 nm). Amino acids occupy only ∼2% of the multimer and protomer volume, compared with 98% for serum albumin and 35% for fibrinogen. VWF treatment with guanidine·HCl, which increases VWF susceptibility to proteolysis by ADAMTS-13, causes local structural changes at length scales <10 nm without altering protein Rg. Treatment of multimer but not protomer VWF with random homobifunctional linker BS3 prior to reduction of intermonomer disulfide linkages and Western blotting reveals a pattern of dimer and trimer units that indicate the presence of stable intermonomer non-covalent interactions within the multimer. Overall, multimeric VWF appears to be a loosely packed ellipsoidal protein with non-covalent interactions between different monomer units stabilizing its solution structure. Local, and not large scale, changes in multimer conformation are sufficient for ADAMTS-13-mediated proteolysis.