Interfacial rheology of linearly growing polyelectrolyte multilayers at the water-air interface: from liquid to solid viscoelasticity.

Despite the long history of investigations of polyelectrolyte multilayer formation on solid or liquid surfaces, important questions remain open concerning the construction of the first set of layers. These are generally deposited on a first anchoring layer of different chemistry, influencing their construction and properties. We propose here an in-depth investigation of the formation of NaPSS/PAH multilayers at the air/water interface in the absence of a chemically different anchoring layer, profiting from the surface activity of NaPSS. To analyse the mechanical properties of the different layers, we combine recently established analysis techniques of an inflating/deflating bubble exploiting simultaneous shape and pressure measurement: bubble shape elastometry, general stress decomposition and capillary meniscus dynanometry. We complement these measurements by interfacial shear rheology. The obtained results allow us to confirm, first of all, the strength of the aforementioned techniques to characterize complex interfaces with non-linear viscoelastic properties. Furthermore, their sensitivity allows us to show that the multilayer properties are highly sensitive to the temporal and mechanical conditions under which they are constructed and manipulated. We nevertheless identify a robust trend showing a clear transition from a liquid-like viscoelastic membrane to a solid-like viscoelastic membrane after the deposition of 5 layers. We interpret this as the number of layers required to create a fully connected multilayer, which is consistent with previous results obtained on solid or liquid interfaces.

PEG-in-PDMS drops stabilised by soft silicone skins as a model system for elastocapillary emulsions with explicit morphology control.

HYPOTHESIS: The morphology of ordinary macro-emulsions is controlled by their high interfacial energies, i.e., by capillarity, leading to well-known structural features which can be tuned only over a narrow range. We claim here that a more explicit control over a much wider range of morphologies can be obtained by producing "elastocapillary emulsions" in which interfacial elasticity acts simultaneously with interfacial tension. EXPERIMENTS: We develop a model-system composed of PEG-in-PDMS emulsions, in which a catalyst diffuses from the PEG drops into the silicone matrix containing two reactive silicone polymers, which are cross-linked in a non-reactive silicone matrix to form a silicone gel of controlled thickness and mechanical properties on the drop surface. We characterise the cross-linking process of the gel in bulk and at the interface, and we analyse the skin growth kinetics. We then use the obtained understanding to produce emulsions with controlled elastocapillary interfaces using in-flow-chemistry in a purpose-designed millifluidic circuit. FINDINGS: We show that this approach allows to create interfaces over the full range of elastocapillary properties, and that very different emulsion morphologies can be generated depending on whether capillarity or elasticity dominates. These findings advance our fundamental understanding of the morphology of emulsions with complex interfaces, and they are of importance for the design of polymerised High Internal Phase Emulsions (polyHIPEs) with original structure/property relations. They will also be useful for the design of silicone capsules with fine-tuned mechanical properties.

Fast and efficient shear-force assisted production of covalently functionalized oxide nanosheets.

HYPOTHESIS: While controlled and efficient exfoliation of layered oxides often remains a time consuming challenge, the surface modification of inorganic nanosheets is of outmost importance for future applications. The functionalization of the bulk material prior to exfoliation should allow the application of tools developped for Van der Waals materials to directly produce functionalized oxide nanosheets. EXPERIMENTS: The Aurivillius phase Bi2SrTa2O9 is functionalized by a linear aliphatic phosphonic acid via microwave-assisted reactions. The structure of the hybrid material and the coordination of the phosphonate group is scrutinized, notably by Pair Distribution Function. This functionalized layered oxide is then exfoliated in one hour in organic solvent, using high shear force dispersion. The obtained nanosheets are characterized in suspension and as deposits to check their chemical integrity. FINDINGS: The covalent functionalization decreases the electrostatic cohesion between the inorganic layers leading to an efficient exfoliation in short time under shearing. The functionalization of the bulk material is preserved on the nanosheets upon exfoliation and plays a major role to enable liquid-phase exfoliation and in the stability of the resulting suspensions. This strategy is very promising for the straighforward preparation of functionalized nanosheets, paving the way for versatile design of new (multi)functional hybrid nanosheets for various potential applications.

Towards a rational morphology control of frozen copolymer aggregates.

Kinetically frozen copolymer micelles are commonly prepared by confining amphiphilic block copolymers in the evaporating dispersed phase of oil-in-water emulsions. We revisit the mechanisms of this process by examining its successive steps separately: the formation of the solvent/water interface, the emulsification, the solvent evaporation and the formation of aggregates. We bring into evidence that: (i) spontaneous water-in-solvent emulsification, i.e., the formation of a double emulsion, is a necessary step for the subsequent assembly of the copolymers into kinetically frozen aggregates with certain morphologies far from equilibrium. (ii) Equilibration of the copolymer conformation at the solvent-water interfaces is a relatively slow process that can be outpaced, or even quenched before completion, by fast solvent evaporation rates. (iii) Rather than being dictated by the packing parameter at equilibrium, the morphology of the aggregates is determined by the effective copolymer conformation at the solvent-water interface when they form. (iv) Ultra-long worm-like micelles do not form by a direct digitation of the dispersed oil phase into the water continuous phase but through the inversion of the double emulsion. From these findings, we design a simple setup that allows us to control the morphology of the frozen aggregates obtained from a given copolymer composition by simply tuning the solvent evaporation rate.

Intravenous and intratumoral injection of Pluronic P94: The effect of administration route on biodistribution and tumor retention.

Pluronics P94 are block-copolymer showing prolonged circulation time and tumor-cell internalization in vitro, suggesting a potential for tumor accumulation and as a drug carrier. Here we report the results of the radiolabeled-P94 unimers (P94-111In-DTPA) on tumor uptake/retention and biodistribution after intravenous and intratumoral injection to tumor-bearing mice. Intravenous administration results in a high radioactive signal in the liver; while in tumor and other healthy tissues only low levels of radioactivity could be measured. In contrast, the intratumoral injection of P94 resulted in elevated levels of radioactivity in the tumor and low levels in other organs, including the liver. Independently from the injection route, the tumor tissue presented long retention of radioactivity. The minimal involvement of off-target tissues of P94, together with the excellent tracer retention over-time in the tumor designates Pluronic P94 copolymer as a highly promising carrier for anti-tumor drugs.

A facile approach for the fabrication of 2D supermicelle networks.

A novel and facile approach to fabricating well-organized macroscopic 2D networks of cylindrical micelles is reported, based on transfer printing and thermal welding of aligned supramolecular micelles of block copolymers. This versatile approach provides a new strategy for fabricating functional 2D superstructures with a higher level of order.

SPECT/CT Imaging of Pluronic Nanocarriers with Varying Poly(ethylene oxide) Block Length and Aggregation State.

Optimal biodistribution and prolonged circulation of nanocarriers improve diagnostic and therapeutic effects of enhanced permeability and retention-based nanomedicines. Despite extensive use of Pluronics in polymer-based pharmaceuticals, the influence of different poly(ethylene oxide) (PEO) block length and aggregation state on the biodistribution of the carriers is rather unexplored. In this work, we studied these effects by evaluating the biodistribution of Pluronic unimers and cross-linked micelles with different PEO block size. In vivo biodistribution of (111)In-radiolabeled Pluronic nanocarriers was investigated in healthy mice using single photon emission computed tomography. All carriers show fast uptake in the organs from the reticuloendothelial system followed by a steady elimination through the hepatobiliary tract and renal filtration. The PEO block length affects the initial renal clearance of the compounds and the overall liver uptake. The aggregation state influences the long-term accumulation of the nanocarriers in the liver. We showed that the circulation time and elimination pathways can be tuned by varying the physicochemical properties of Pluronic copolymers. Our results can be beneficial for the design of future Pluronic-based nanomedicines.

Interactions of Pluronic nanocarriers with 2D and 3D cell cultures: Effects of PEO block length and aggregation state.

This work reveals how the physicochemical properties of Pluronic block copolymers influence significantly their interactions with cancer cells, whether in monolayer or spheroid cultures, and how different clinical applications can be foreseen. Two-dimensional (2D) and three-dimensional (3D) cell culture models were used to investigate the interactions of Pluronic carriers with different PEO block length and aggregation state (unimers versus cross-linked micelles) in HeLa and U87 cancer cells. Stabilized micelles of Pluronic P94 or F127 were obtained by polymerization of a crosslinking agent in the micelles hydrophobic core. Nanocarriers were functionalized with a fluorescent probe for visualization, and with a chelator for radiolabeling with Indium-111 and gamma-quantification. The 2D cell models revealed that the internalization pathways and ultimate cellular localization of the Pluronic nanocarriers depended largely on both the PEO block size and aggregation state of the copolymers. The smaller P94 unimers with an average radius of 2.1nm and the shortest PEO block mass (1100gmol(-1)) displayed the highest cellular uptake and retention. 3D tumor spheroids were used to assess the penetration capacity and toxicity potential of the nanocarriers. Results showed that cross-linked F127 micelles were more efficiently delivered across the tumor spheroids, and the penetration depth depends mostly on the transcellular transport of the carriers. The Pluronic P94-based carriers with the shortest PEO block length induced spheroid toxicity, which was significantly influenced by the spheroid cellular type.

Lack of a unique kinetic pathway in the growth and decay of Pluronic micelles.

We report kinetic experiments on dilute brine solutions of P84, P94 and P104 Pluronic copolymer micelles. The growth and the decay of micelles after temperature steps are measured by non-standard time resolved multi-angle photon correlation spectroscopy. Several concurrent mechanisms are at work during the very slow equilibration of solutions, namely insertion/expulsion of unimers, aggregation/dissociation of micellar aggregates, and fusion/budding of micellar aggregates. Their relative rates determine both the kinetic pathways and the morphologies of the micellar assemblies, which depend markedly on modest changes in the copolymer molecular weight. For the typical Pluronic copolymers investigated here, none of these elementary processes can be neglected if the resulting morphology is to be explained. This feature imposes multiple kinetic behaviours where growth and decay of Pluronic micelles become strongly dependent on the thermal history. We point out to some possible shortcomings in the studies of micellar growth kinetics by light scattering techniques. Extensive time-resolved multiangle measurements are a prerequisite for avoiding these pitfalls.

Cytotoxicity and internalization of Pluronic micelles stabilized by core cross-linking.

A UV-cross-linkable agent was incorporated and polymerized in Pluronic micelle core to create an interpenetrating polymer network (IPN) of poly(pentaerythritol tetraacrylate). This stabilization prevented micelle disruption below the critical micelle temperature (CMT) and concentration (CMC), while maintaining the integrity of the PEO corona and the hydrophobic properties of the PPO core. The prepared stabilized spherical micelles of Pluronic P94 and F127 presented hydrodynamic diameters ranging from 40 to 50 nm. The stability of cross-linked Pluronic micelles at 37 °C in the presence of serum proteins was studied and no aggregation of the micelles was observed, revealing the colloidal stability of the system. Cytotoxicity experiments in NIH/3T3 mouse fibroblasts revealed that the presence of the cross-linking agent did not induce any further toxicity in comparison to the respective pure polymer solutions. Furthermore, stabilized micelles of Pluronic P94 were shown to be less toxic than the polymer itself. A hydrophobic fluorescent probe (Nile red) was absorbed in the cross-linked core of pre-stabilized micelles to mimic the incorporation of a poorly water-soluble drug, and the internalization and intracellular localization of Nile red was studied by confocal microscopy at different incubation times. Overall, the results indicate that Pluronic micelles stabilized by core cross-linking are capable of delivering hydrophobic components physically entrapped in the micelles, thus making them a potential candidate as a delivery platform for imaging or therapy of cancer.

Wall slip, shear banding, and instability in the flow of a triblock copolymer micellar solution.

The shear flow of a triblock copolymer micellar solution (PEO-PPO-PEO Pluronic P84 in brine) is investigated using simultaneous rheological and velocity profile measurements in the concentric cylinder geometry. We focus on two different temperatures below and above the transition temperature T{c} which was previously associated with the apparition of a stress plateau in the flow curve. (i) At T=37.0 degrees CT{c}, the stress plateau is shown to correspond to stationary shear-banded states characterized by two high shear rate bands close to the walls and a very weakly sheared central band, together with large slip velocities at the rotor. In both cases, the high shear branch of the flow curve is characterized by flow instability. Interpretations of wall slip, three-band structure, and instability are proposed in light of recent theoretical models and experiments.