Imperfect dissolution in nonionic block copolymer and surfactant mixtures.

Self-assembled copolymer micelles have been widely explored for numerous applications including cosmetic formulations and detergency, drug delivery, and agriculture. In many of these technologies at least trace amounts of surfactants and detergents are present, yet little is known regarding their effect on the copolymer micelle structure. In this paper we examine the influence of a nonionic micelle-forming surfactant, Triton X-100, on spherical, nonionic polymeric micelles composed of poly(butadiene)-co-poly(polyethylene oxide). Using cryo-TEM we find that relatively small surfactant concentrations (less than 1:1 molar ratio) are sufficient to disrupt the copolymer assemblies, and to yield, via dimerization, mixed polymer-surfactant micelles with characteristic diameters. Saturation of the polymeric micelles is reached with approximately 3 mM surfactant (1:8 mol ratio). Upon saturation, and in high surfactant excess, coexistence of two homogeneous micellar populations is found: saturated polymer-surfactant micelles, and much smaller micelles of pure surfactant. The lack of complete demicellization of the polymeric micelles is explained by packing constraints of the polymer hydrophobic chains by the added surfactant. This behavior is found to be characteristic of polymeric molecules with hydrophobic-to-hydrophilic molecular weight ratio close to, or exceeding, 0.75. We further found that structural transitions in polymer-surfactant mixtures are fast, and the systems reach equilibrium at time scales characteristic to the small molecule, in contrast with the slow equilibration in polymer-polymer mixtures.

Effect of mixing on the morphology of cylindrical micelles.

Increasing the spontaneous curvature of an amphiphile can lead to a first-order morphology transition from threadlike micelles to a branched network. The two morphologies were linked to entropy-driven topological defects; networks are dominated by Y-junctions, while linear threadlike structures are dominated by spherical end-caps. In this paper we investigate the effect of mixing on the morphological transitions in nonionic amphiphilic systems. We find that mixed equilibrium structures are obtained within seconds; these mixed cylindrical structures display comparable numbers of end-caps and branch points, resulting in a novel 'short armed' branched (SAB) morphology. Quite surprisingly, the probability of either defect (end-caps or branch points) is independent of composition, so that neither a first-order nor a second-order morphological transition is observed. A possible explanation may be local demixing of the two amphiphilic components, which adds a degree of freedom and thus enables the formation of a unique morphology that cannot be obtained in single-component systems. We further find that within a relatively large composition range phase equilibrium exists between vesicles, SAB micelles, and spherical micelles.

Micellization of bovine beta-casein studied by isothermal titration microcalorimetry and cryogenic transmission electron microscopy.

The association behavior, critical micellization concentration (CMC), and enthalpy of demicellization (DeltaHdemic) of bovine beta-casein were studied, for the first time by isothermal titration calorimetry, in a pH 7.0 phosphate buffer with 0.1 ionic strength and in pure water. In the buffer solutions, the CMC decreased asymptotically from 0.15 to 0.006 mM as the temperature was raised from 16 to 45 degrees C. DeltaHdemic decreased with increasing temperature between 16 and 28 degrees C but increased from 28 to 45 degrees C. Thermodynamic analysis below 30 degrees C is consistent with the Kegeles shell model, which suggests a stepwise association process. At higher temperatures, this model exhibits limitations, and the micellization becomes much more cooperative. The CMC values in water, measured between 17 and 28 degrees C, decreased with increasing temperature and, expectedly, were higher than those found in the buffer solutions. beta-Casein micelles were visualized and characterized, for the first time in their hydrated state, using advanced digital-imaging cryogenic transmission electron microscopy. The images revealed small, oblate micelles, about approximately 13 nm in diameter. The micelles shape and dimensions remained nearly constant in the temperature range of 24-35 degrees C.

Synthesis and characterization of mPEG-PLA prodrug micelles.

Polymeric prodrugs of mPEG-PLA-haloperidol (methoxypoly(ethylene glycol)-b-poly(lactic acid)) can self-assemble into nanoscale micelle-like structures in aqueous solutions. mPEG-PLA-haloperidol was prepared and characterized using 1H and 13C NMR. The conjugation efficiency was found to be 64.8 +/- 21%. Micelles that form spontaneously upon solubilization of the mPEG-PLA and the polymeric prodrugs in water were characterized using a variety of techniques. The mPEG-PLA and prodrug micelles were found to have diameters of 28.73 +/- 1.45 and 49.67 +/- 4.29 nm, respectively, using dynamic light scattering (DLS). The micelle size and polydispersity were also evaluated with cryogenic transmission electron microscopy (cryo-TEM) and were consistent with the DLS results. Cryo-TEM and proton NMR confirmed that the micelles were spherical in shape. DLS was also used to determine the aggregation numbers of the micelles. The aggregation numbers ranged from 351 to 603. The change in aggregation number was dependent on the total drug incorporation into the micelle core. Critical micelle concentrations were determined for the various micelle/drug formulations and found to range from 3 to 14 microg/mL. Finally, drug was incorporated into the micelle core using the conjugate, free drug with a saturated aqueous phase during production, or a combination of both techniques. Drug incorporation could be increased from 3% to 20% (w/w) using the different formulations.