Peculiar Behavior of Methyl Methacrylate Emulsion Polymerization-Induced Self-Assembly Mediated by RAFT Using Poly(Methacrylic Acid) Macromolecular Chain Transfer Agent.

Reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization of methyl methacrylate (MMA) is successfully performed in water in the presence of a poly(methacrylic acid) (PMAA) macromolecular chain transfer agent (macroCTA) leading to the formation of self-stabilized PMAA-b-PMMA amphiphilic block copolymer particles. At pH 3.7, the reactions are well-controlled with narrow molar mass distributions. Increasing the initial pH, particularly above 5.6, results in a partial loss of reactivity of the PMAA macroCTA. The effect of the degree of polymerization (DPn) of the PMMA block, the solids content, the nature of the hydrophobic segment, and the pH on the morphology of the obtained diblock copolymer particles is then investigated. Worm-like micelles are formed for a DPn of PMMA of 20 (PMMA20), while "onion-like" particles and spherical vesicles are obtained for PMMA30 and PMMA50, respectively. In contrast, spherical particles are obtained for the DPns higher than 150. This unusual evolution of particle morphologies upon increasing the DPn of the PMMA block seems to be related to hydrogen bonds between hydrophilic MAA and hydrophobic MMA units.

Spheroplexes: Hybrid PLGA-cationic lipid nanoparticles, for in vitro and oral delivery of siRNA.

Vectorized small interfering RNAs (siRNAs) are widely used to induce gene silencing. Among the delivery systems used, lipid-based particles are the most effective. Our objective was the development of novel lipid-polymer hybrid nanoparticles, from lipoplexes (complexes of cationic lipid and siRNAs), and poly (lactic-co-glycolic acid) (PLGA), using a simple modified nanoprecipitation method. Due to their morphology, we called these hybrid nanoparticles Spheroplexes. We elucidated their structure using several physico-chemical techniques and showed that they are composed of a hydrophobic PLGA matrix, surrounded by a lipid envelope adopting a lamellar structure, in which the siRNA is complexed, and they retain surface characteristics identical to the starting nanoparticles, i.e. lipoplexes siRNA. We analyzed the composition of the particle population and determined the final percentage of spheroplexes within this population, 80 to 85% depending on the preparation conditions, using fluorescent markers and the ability of flow cytometry to detect nanometric particles (approximately 200 nm). Finally, we showed that spheroplexes are very stable particles and more efficient than siRNA lipoplexes for the delivery of siRNA to cultured cells. We administered spheroplexes contain siRNAs targeting TNF-α to mice with ulcerative colitis induced by dextran sulfate and our results indicate a disease regression effect with a response probably mediated by their uptake by macrophages / monocytes at the level of lamina propria of the colon. The efficacy of decreased level of TNF-α in vivo seemed to be an association of spheroplexes polymer-lipid composition and the specific siRNA. These results demonstrate that spheroplexes are a promising hybrid nanoparticle for the oral delivery of siRNA to the colon.

Ethylene-Coordinative Chain-Transfer Polymerization-Induced Self-Assembly (CCTPISA).

Block copolymers based on ethylene (E) and butadiene (B) were prepared using the ansa-bis(fluorenyl) complex {Me2 Si(C13 H8 )2 Nd(BH4 )2 Li(THF)}2 in combination with (n-Bu)(n-Oct)Mg (BOMAG) as a chain-transfer agent. The diblock copolymers incorporating a soft poly(ethylene-co-butadiene) segment, called ethylene butadiene rubber (EBR), and a hard polyethylene (PE) one were obtained by simply adjusting the different feeds of monomers during the polymerization. The soluble EBR block was formed first by feeding the catalytic system dissolved in toluene at 70 °C with a mixture of ethylene and butadiene (E/B molar ratio 80 : 20). Then the feeding was stopped leading to the consumption of a large part of the residual monomers. The reactor was finally fed with ethylene to form the PE block. By varying the molar mass of the latter, it is shown that the resulting soft-b-hard block copolymers can self-assemble simultaneously to the growth of the PE block in agreement with a polymerization-induced self-assembly (PISA) mechanism. The self-assembly is discussed considering the reaction conditions, the crystallization of the PE block, and the polymerization mechanism involved.

Synergetic Effect of Water-Soluble PEG-Based Macromonomers and Cellulose Nanocrystals for the Stabilization of PMMA Latexes by Surfactant-Free Emulsion Polymerization.

The combination of cellulose nanocrystals (CNCs) and poly(ethylene glycol) methyl ether methacrylate (PEGMA) was evaluated to synthesize stable latexes by surfactant-free emulsion polymerization of methyl methacrylate (MMA). Cellulose-particle interaction was provided due to the dual role of PEGMA, acting as water-soluble comonomer with MMA under emulsion polymerization conditions and able to interact with CNCs, recovered from sulfuric acid hydrolysis (H2SO4-CNCs). After preliminary experiments designed to validate the affinity between CNCs and PEG-stabilized PMMA particles obtained by MMA/PEGMA emulsion copolymerization, the effect of the PEGMA content and molar mass and also of the content of CNCs on the kinetics of the polymerization and the stability of the latexes were investigated. The use of PEGMA300 (Mn = 300 g mol-1, 2-10 wt %) allowed the formation of a stable latex, however, with a broad particle size distribution and the presence of both small (ca. 25-50 nm) and large (ca. 425-650 nm) particles (at 10 wt %, Dn = 278 nm and Dw/Dn = 1.34). Increasing the molar mass of PEGMA (PEGMA950 or PEGMA2080) significantly increased the fraction of small particles. This was explained by the nucleation and growth of small polymer particles adsorbed at the CNCs' surface, resulting in a particular organization where the CNCs were covered by several polymer particles. The influence of the initial amount of CNCs in these systems was finally evidenced, the polymerization being faster as the content of CNCs increased, but only the latexes prepared with 2 and 5 wt % of CNCs were stable.

Ethylene Polymerization-Induced Self-Assembly (PISA) of Poly(ethylene oxide)-block-polyethylene Copolymers via RAFT.

Poly(ethylene oxide) (PEO) with dithiocarbamate chain ends (PEO-SC(=S)-N(CH3 )Ph and PEO-SC(=S)-NPh2 , named PEO-1 and PEO-2, respectively) were used as macromolecular chain-transfer agents (macro-CTAs) to mediate the reversible addition-fragmentation chain transfer (RAFT) polymerization of ethylene in dimethyl carbonate (DMC) under relatively mild conditions (80 °C, 80 bar). While only a slow consumption of PEO-1 was observed, the rapid consumption of PEO-2 led to a clean chain extension and the formation of a polyethylene (PE) segment. Upon polymerization, the resulting block copolymers PEO-b-PE self-assembled into nanometric objects according to a polymerization-induced self-assembly (PISA).

In-vitro evaluation of solid lipid nanoparticles: Ability to encapsulate, release and ensure effective protection of peptides in the gastrointestinal tract.

Peptides are rarely orally administrated due to rapid degradation in the gastrointestinal tract and low absorption at the epithelial border. The objective of this study was to encapsulate a model water-soluble peptide in biodegradable and biocompatible solid lipid-based nanoparticles, i.e. Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) in order to protect it from metabolic degradation. Leuprolide (LEU) and a LEU-docusate Hydrophobic Ion Pair (HIP) were encapsulated in SLN and NLC by High Pressure Homogenization. The particles were characterized regarding their Encapsulation Efficiency (EE), size, morphology, peptide release in FaSSIF-V2, and protective effect towards proteases. Nanoparticles of 120 nm with platelet structures were obtained. Formation of HIP led to a significant increase in LEU EE. Particle size was moderately affected by the presence of simulated fluids. Nonetheless, an important burst release was observed upon dispersion in FaSSIF-V2. NLC were able to improve LEU-HIP resistance to enzymatic degradation induced by trypsin but presented no advantages in presence of α-chymotrypsin. SLN provided no protection regarding both proteases. Despite an increased amount of encapsulated peptide in solid lipid-based nanoparticles following HIP formation, the important specific surface area linked to their platelet structures resulted in an important peptide release upon dispersion in FaSSIF-V2 and limited protection towards enzymatic degradation.

Pickering emulsions stabilized by charged nanoparticles.

The stabilization of o/w Pickering emulsions in cases of weak adsorption of solid particles at the surface of oil droplets is addressed. Though the adsorption is usually very strong and irreversible when partial wetting conditions are fulfilled, electrostatic repulsions between charged solid particles act against the adsorption. The regime of weak adsorption was reached using charged silica nanoparticles at high pH and low ionic strength. O/w Pickering emulsions of the diisopropyl adipate oil were stabilized by colloidal nanoparticles of Ludox® AS40 consisting of non-aggregated particles of bare silica (hydrophilic). The combination of stability assessment, droplet size and electrokinetic potential measurements at various pH values, adsorption isotherms and cryo-SEM observations of the adsorbed layers disclosed the specificities of the stabilization of Pickering emulsions by adsorption of solid nanoparticles against strong electrostatic repulsions. Not only the long-term stability of emulsions was poor under strong electrostatic repulsions at high pH, but emulsification failed since full dispersion of oil could not be achieved. Emulsion stability was ensured by decreasing electrostatic repulsions by lowering the pH from 9 to 3. Stable emulsions were stabilized by a monolayer of silica particles at 54% coverage of the oil droplet surface at low silica content and an adsorption regime as multilayers was reached at higher concentrations of silica although there was no aggregation of silica in the bulk aqueous phase.

Erratum: Dynamic Stratification in Drying Films of Colloidal Mixtures [Phys. Rev. Lett. 116, 118301 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.116.118301.

Publisher's Note: Dynamic Stratification in Drying Films of Colloidal Mixtures [Phys. Rev. Lett. 116, 118301 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.116.118301.

Temperature Response of Rhodamine B-Doped Latex Particles. From Solution to Single Particles.

Nanoparticle-based temperature imaging is an emerging field of advanced applications. Herein, the sensitivity of the fluorescence of rhodamine B-doped latex nanoparticles toward temperature is described. Submicrometer size latex particles were prepared by a surfactant-free emulsion polymerization method that allowed a simple and inexpensive way to incorporate rhodamine B into the nanoparticles. Also, rhodamine B-coated latex nanoparticles dispersed in water were prepared in order to address the effect of the dye location in the nanoparticles on their temperature dependence. A better linearity of the temperature dependence emission of the rhodamine B-embedded latex particles, as compared to that of free rhodamine B dyes or rhodamine B-coated latex particles, is observed. Temperature-dependent fluorescence measurements by fluorescent confocal microscopy on individual rhodamine B-embedded latex particles were found similar to those obtained for fluorescent latex nanoparticles in solution, indicating that these nanoparticles could be good candidates to probe thermal processes as nanothermometers.

Dynamic Stratification in Drying Films of Colloidal Mixtures.

In simulations and experiments, we study the drying of films containing mixtures of large and small colloidal particles in water. During drying, the mixture stratifies into a layer of the larger particles at the bottom with a layer of the smaller particles on top. We developed a model to show that a gradient in osmotic pressure, which develops dynamically during drying, is responsible for the segregation mechanism behind stratification.