Proper Determination of Phase Diagrams while Nanoprecipitating Oils.

The Ouzo effect is a generic process to generate colloidal dispersions from a variety of solutes. Whereas phase diagrams have been quite easily established when nanoprecipitating polymers, the case of oils is less straightforward. Indeed, the short-term stability of generated nanodroplets in water/solvent mixtures complexifies the identification of the diagram boundaries. This article proposes two complementary methods, namely, fluorescence microscopy and dynamic light scattering, to determine with fair accuracy Ouzo limits in ternary systems oil/solvent/nonsolvent, without and with a surfactant, respectively. This accuracy in PD determination opens the way to a better understanding and control of the aggregation events during the nanoprecipitation process.

Poly(vinyl alcohol)s and Their Glycoderivatives as Efficient Shell-Builders of Nanocapsules by Nanoprecipitation.

Poly(vinyl alcohol)s (PVAs) are very popular dispersants for the construction of colloids and common shell-constituents of microcapsules but remain mostly unexplored as building blocks for the design of nanocapsules through nanoprecipitation or other processes. Herein, we first show that model commercial PVAs and oils can be concomitantly engaged in solvent-shifting procedures to give rise to oil-filled nanocapsules in one step. Next, we report the synthesis of precisely defined water-soluble glyco-PVAs by reversible addition-fragmentation chain transfer (RAFT) copolymerization of 6-O-vinyladipoyl-d-glucopyranose and vinyl chloroacetate and selective alcoholysis reactions. We finally demonstrate that these glycopolymers are excellent candidates for the straightforward conception of oil- and drug-filled, surface- and/or core-tagged, stealth, and degradable nanocapsules by nanoprecipitation.

Modulation of Oil/Polymer Nanocapsule Size via Phase Diagram-Guided Microfluidic Coprecipitation.

Flow-based nanoprecipitation of different solutes via rapid mixing of two miscible liquids is a scalable strategy for manufacturing nanoparticles with various shapes and morphologies. Controlling the size of nanoparticles in flow-based nanoprecipitation, however, is often left to empirical variations in the flow rate ratios or the total flow rate of the two streams. In this work, we investigate the coprecipitations of oil and polymer to form nanocapsules via the Ouzo effect using glass capillary microfluidics across a range of mixing conditions. In the range of flow rates studied, the two streams mix convectively in micro-vortices formed at the junction of the two stream inlets. Using computational fluid dynamics simulations and glass capillary microfluidic nanoprecipitation, we establish a relationship between the precipitation conditions occurring experimentally in situ and the location on the ternary Ouzo phase diagram where precipitation is taking place. We find that a key variable in the resulting average diameter of the fabricated capsules is the degree of supersaturation experienced by both the oil and the polymer in the vortex zone of the device, showing a strong correlation between the two values. The control over the nanocapsule size by varying the extent of supersaturation of both precipitants is demonstrated by using two oils having distinct phase diagrams. This work provides a systematic approach to controlling the size of nanoparticles fabricated via continuous nanoprecipitation by linking the in situ flow conditions to ternary phase diagram behavior, enabling accurate control over nanocapsule size.

Zwitterionic Silicone Materials Derived from Aza-Michael Reaction of Amino-Functional PDMS with Acrylic Acid.

Supramolecular zwitterionic silicones are synthesized by aza-Michael reaction between acrylic acid and amine-functional polydimethylsiloxanes. The in-depth characterization of this chemistry, applied for the first time to silicones, is investigated first with model alkylamines (hexylamine, 2-ethylhexylamine and N-propylethylenediamine), a model oligosiloxane (3-aminopropylmethyl bis(trimethylsiloxy)silane), and finally various amino-polysiloxanes. It is shown that after a first acid-base reaction resulting in ionic pairing, aza-Michael addition proceeds smoothly in mild conditions (50 °C, 1-week reaction). Both monoadducts and di-adducts, together with residual amine, are observed by NMR. The supramolecular assembly of the thus-created zwitterionic moieties is highlighted by a concomitant increase in viscosity and phase separation, as observed by transmission electron microscopy, bringing an additional glass transition at -40 °C assigned to highly polar ionic clusters. Below the stoichiometry in acrylic acid, all zwitterionic silicones follow the same classical behavior of nonentangled polymers according to the Rouse model, whereas upon introducing an excess of acrylic acid to amino groups, an enhancement of the elasticity is observed. Finally, silicone elastomers with solid-like behavior and elastomeric mechanical properties are obtained using a high molar mass polymer bearing bifunctional N-(2-aminoethyl)-3-aminopropyl units that favor a high degree of physical crosslinking.

Cationic Polymerization of Hexamethylcyclotrisiloxane in Excess Water.

Ring-opening ionic polymerization of cyclosiloxanes in dispersed media has long been discovered, and is nowadays both fundamentally studied and practically used. In this short communication, we show some preliminary results on the cationic ring-opening polymerization of hexamethylcyclotrisiloxane (D3), a crystalline strained cycle, in water. Depending on the catalyst or/and surfactants used, polymers of various molar masses are prepared in a straightforward way. Emphasis is given here on experiments conducted with tris(pentafluorophenyl)borane (BCF), where high-molar polymers were generated at room temperature. In surfactant-free conditions, µm-sized droplets are stabilized by silanol end-groups of thus generated amphiphilic polymers, the latter of which precipitate in the course of reaction through chain extension. Introducing various surfactants in the recipe allows generating smaller emulsions in size with close polymerization ability, but better final colloidal stability, at the expense of low small cycles' content. A tentative mechanism is finally proposed.

Functional Hybrid Glyconanocapsules by a One-Pot Nanoprecipitation Process.

Herein, we report on one-pot fabrication of oil-filled nanocapsules wrapped with both RAFT-made glycopolymers and neutral polysaccharides (dextran and pullulan). We have made use of the nanoprecipitation technique, relying on coprecipitation of both oil and polymers in conditions thoroughly established from phase diagrams' interpretation. Mixed mono- or multilayered nanocapsules were obtained through simultaneous or sequential nanoprecipitations, respectively. Incorporation of synthetic glycopolymer chains allows for precisely tailoring the dimensions of the nanocapsules (size and membrane thickness of the polymeric shell), whereas the insertion of polysaccharides enables to tune the (bio)degradability of the nanocapsules. Shell-functionalized and/or core-loaded capsules could also be achieved in a similar one-pot process, by introducing a drug and/or biotin in the organic and aqueous phase, respectively.

Programmable Hierarchical Construction of Mixed/Multilayered Polysaccharide Nanocapsules through Simultaneous/Sequential Nanoprecipitation Steps.

We report here on a one-pot construction of oil-filled hierarchical capsular assemblies using the nanoprecipitation technique. Relying on multicomponent phase diagrams, we show that simultaneous and/or sequential nanoprecipitations involving polymer combinations can be precisely programmed to design a new class of mixed/multilayered multicomponent nanocapsules, with a precise control of the dimensions, shell thickness/composition, and spatial distribution of the building blocks. The simplicity and tunability of this approach are exemplified here with a library of neutral and ionic polysaccharides giving access to a range of functional multilayered nanocarriers of interest for biomedical applications.

A Catalyst Platform for Unique Cationic (Co)Polymerization in Aqueous Emulsion.

Sodium dodecyl benzene sulfonate (DBSNa) surfactants, with a polydisperse and hyperbranched structure, combined with different rare earth metal salts generate highly water-dispersible Lewis acid surfactant combined catalysts (LASCs). This platform of new complexes promotes fast, efficient cationic polymerization of industrially relevant monomers in direct emulsion at moderate temperature. The process described here does not require high shearing, long polymerization time, or large catalyst content. It allows the reproducible generation of high-molar-mass homopolymers of pMOS, styrene, and isoprene, as well as random or multiblock copolymers of the latter two, in a simple and straightforward one-pot reaction.

Simple but precise engineering of functional nanocapsules through nanoprecipitation.

A general, rapid, and undemanding method to generate at will functional oil-filled nanocapsules through nanoprecipitation is reported. On the basis of polymer and hexadecane/water/acetone phase diagrams, the composition can be set so that polymer chains preferentially stick at the interface of the oil droplets to create nanocapsules. The nanocapsules can be decorated with biorelevant molecules (biotin, fluorescent tags, metal nanoparticles) within the shell and loaded with hydrophobic molecules in a simple one-pot procedure.

Cationic polymerization of vinyl monomers in aqueous media: from monofunctional oligomers to long-lived polymer chains.

Polymer latexes are easily prepared on a multimillion ton scale in industry using free radical initiated emulsion and suspension polymerizations in water, a cheap, nonviscous, heat-controlling, and environmentally benign solvent. Until recently, researchers had done little investigation into ionic polymerization because even a small amount of water would easily deactivate the conventional catalysts used in these processes. In the last decade, however, cationic polymerization in aqueous media has emerged as a new and attractive method for controlling the polymerization reactions using mild experimental conditions. This Account reviews the current science of and future outlook for cationic polymerization of vinyl monomers in aqueous media. We particularly emphasize the design and evolution of catalytic systems and the precision synthesis of functional polymers. Early work to tailor the suspension and emulsion cationic polymerizations of reactive monomers such as p-methoxystyrene and vinyl ethers used long-chain strong acids, called INISURF for their dual roles as initiators and surfactants, and lanthanide triflates. These polymerization processes shared two main features: (i) all reactions (initiation, propagation, and termination) occurred at the particle interface; (ii) synthesized polymers have limits on their molecular weight, attributed to the "critical DP" effect, related to the entry of oligomers inside the particles as they become increasingly hydrophobic. The next generation of catalysts, named "Lewis acid-surfactant combined catalysts" (LASC), shifted the polymerization locus from the interface to the inside of the monomer droplets, allowing for the production of long polymer chains. Recently, catalytic systems based on boranes, (BF(3)OEt(2), B(C(6)F(5))(3), (C(6)F(4)-1,2-[B(C(6)F(5))(2)]), and (C(6)F(4)-1,2-[B(C(12)F(8))](2))), have shown great potential in controlling the cationic polymerization in "wet" solution, containing an excess of water relative to Lewis acid, or aqueous media of such industrially important monomers as styrene, cyclopentadiene, and even isobutylene.

Tailored covalent grafting of hexafluoropropylene oxide oligomers onto silica nanoparticles: toward thermally stable, hydrophobic, and oleophobic nanocomposites.

The modification of silica nanoparticles with hexafluoropropylene oxide (HFPO) oligomers has been investigated. HFPO oligomers with two different average degrees of polymerization (DPn = 8 and 15) were first prepared by anionic ring-opening polymerization, deactivated by methanol, and in some cases postfunctionalized by aminopropyl(tri)ethoxysilane or allylamine. The "grafting onto" reactions of these oligomers were then carried out either on bare silica (reaction between a silanol surface and ethoxy-silanized HFPO) or on silica functionalized by amino groups (in an amidation reaction with methyl ester-ended HFPO) or mercapto groups (via the radical addition of allyl-functionalized HFPO). Hybrid nanoparticles thus obtained were characterized by solid-state (29)Si NMR and FTIR spectroscopies as well as elemental and thermogravimetric analyses. The results assessed a significant yield of covalent grafting of HFPO oligomers when performing the hydrolysis-condensation of ethoxylated HFPO on the bare silica surface, compared to the other two methods that merely led to physically adsorbed HFPO chains. Chemically grafted nanohybrids showed a high thermal stability (up to 400 °C) as well as a very low surface tension (typically 5 mN/m) compared to physisorbed complexes.

Nanoprecipitation as a simple and straightforward process to create complex polymeric colloidal morphologies.

Polymeric nanoparticles are highly important functional nanomaterials for a large range of applications from therapeutics to energy. Advances in nanotechnology have enabled the engineering of multifunctional polymeric nanoparticles with a variety of shapes and inner morphologies. Thanks to its inherent simplicity, the nanoprecipitation technique has progressively become a popular approach to construct polymeric nanoparticles with precise control of nanostructure. The present review highlights the great capability of this technique in controlling the fabrication of various polymeric nanostructures of interest. In particular, we show here how the nanoprecipitation of either block copolymers or mixtures of homopolymers can afford a myriad of colloids displaying equilibrium (typically onion-like) or out-of-equilibrium (stacked lamellae, porous cores) morphologies, depending whether the system "freezes" while passing the glass transition or crystallization point of starting materials. We also show that core-shell morphologies, either from polymeric or oil/polymer mixtures, are attainable by this one-pot process. A final discussion proposes new directions to enlarge the scope and possible achievements of the process.

Photopatterning of PDMS Films: Challenging the Reaction between Benzophenone and Silicone Functional Groups.

Direct photopatterning of PDMS (Polydimethylsiloxane) through benzophenone photo-inhibition has received great interest in recent years. Indeed, the simplicity and versatility of this technique allows for easy processing of micro-canals, or local control of PDMS mechanical properties. Surprisingly, however, the chemical reactions between silicone hydride and/or silicone vinyl groups and benzophenone have only been assessed through qualitative methods (e.g., Attenuated total reflection fourier transform infrared). In this communication, the previously proposed reaction pathways are challenged, using nuclear magnetic resonance (NMR) spectroscopy and size exclusion chromatography (SEC) monitoring. A different mechanism depicting the role of benzophenone irradiation on the polyaddition reaction of silicone formulations is proposed, and a simplified procedure involving aromatic solvent is finally disclosed.

Nanocapsules Produced by Nanoprecipitation of Designed Suckerin-Silk Fusion Proteins.

Herein, we report on the precise design of a modular fusion protein amenable to the construction of nanocapsules by nanoprecipitation. The central squid suckerin-derived peptide block provides structural stability, whereas both termini from spider silk fibroins make the protein highly soluble at physiological pH, a critical requirement for the nanoprecipitation process. With this design, nanocapsules consisting of fusion protein shells and oily cores with sizes in the range of 190-250 nm are built in a straightforward manner.

Oligomerization of electron-deficient vinyl monomers through an ate-complex mechanism: a new role for b(c(6) f(5) )(3) lewis Acid.

The Lewis acid B(C(6) F(5) )(3) in combination with hydrosilanes exhibits remarkable activity in the oligomerization of sulfone- and phosphonate-based monomers. This process opens new routes to high-tech silicone-based materials, i.e., thermoplastic elastomers and heat-resistant polysiloxanes.

Central Role of Bicarbonate Anions in Charging Water/Hydrophobic Interfaces.

Aqueous interfaces are ubiquitous in Nature and play a fundamental role in environmental or biological processes or modern nanotechnologies. These interfaces are negatively charged, and despite several decades of research, the rationale behind this phenomenon is still under debate. Two main controversial schools of thought argue on this issue; the first relies on the adsorption of hydroxide anions on hydrophobic surfaces, whereas the second one supports a self-rearrangement of water molecules at the interface bearing hydronium ions. Here, we report on two series of independent experimental studies (nanoprecipitation and interfacial tension measurements) that demonstrate that in the pH 5-10 range the negative interfacial charge of the colloids mostly stems from bicarbonate ions, whereas at lower and higher pH, protons and hydroxide ions contribute, with bicarbonate ions, to the interfacial charging. This new interpretation complies with previous studies and opens new perspectives to this striking physical chemical issue.

General and Scalable Approach to Bright, Stable, and Functional AIE Fluorogen Colloidal Nanocrystals for in Vivo Imaging.

Fluorescent nanoparticles built from aggregation-induced emission-active organic molecules (AIE-FONs) have emerged as powerful tools in life science research for in vivo bioimaging of organs, biosensing, and therapy. However, the practical use of such biotracers has been hindered owing to the difficulty of designing bright nanoparticles with controlled dimensions (typically below 200 nm), narrow size dispersity and long shelf stability. In this article, we present a very simple yet effective approach to produce monodisperse sub-200 nm AIE fluorescent organic solid dispersions with excellent redispersibility and colloidal stability in aqueous medium by combination of nanoprecipitation and freeze-drying procedures. By selecting polymer additives that simultaneously act as stabilizers, promoters of amorphous-crystalline transition, and functionalization/cross-linking platforms, we demonstrate a straightforward access to stable nanocrystalline FONs that exhibit significantly higher brightness than their amorphous precursors and constitute efficient probes for in vivo imaging of the normal and tumor vasculature. FONs design principles reported here are universal, applicable to a range of fluorophores with different chemical structures and crystallization abilities, and are suitable for high-throughput production and manufacturing of functional imaging probes.

Modular construction of single-component polymer nanocapsules through a one-step surfactant-free microemulsion templated synthesis.

Formation of O/W surfactant-free microemulsions from water/oil/acetone ternary systems is exploited to construct precisely-defined shell-functionalized core-loaded nanocapsules with tunable diameters (ranging from 50 to 190 nm) in one step.