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The assembly of oppositely charged block copolymers, containing small thermoresponsive moieties, was investigated as a function of salt concentration and temperature. Aqueous solutions of poly-[N-isopropylacrylamide]-b-poly[dimethylaminoethyl methacrylate] (NIPAM44-b-DMAEMA216) and PNIPAM-b-poly[acrylic acid]-b-PNIPAM (NIPAM35-b-AA200-b-NIPAM35) were mixed in equal charge stoichiometry, and analysed by light scattering (LS), NMR spectroscopy and small angle X-ray scattering (SAXS). At room temperature, two different micelle morphologies were found at different salt concentrations. At NaCl concentrations below 0.75 M, complex coacervate core micelles (C3M) with a PNIPAM corona were formed as a result of interpolyelectrolyte complexation. At NaCl concentrations exceeding 0.75 M, the C3M micelles inverted into PNIPAM cored micelles (PCM), containing a water soluble polyelectrolyte corona. This behavior is ascribed to the salt concentration dependence of both the lower critical solution temperature (LCST) of PNIPAM, and the complex coacervation. Above 0.75 M NaCl, the PNIPAM blocks are insoluble in water at room temperature, while complexation between the polyelectrolytes is prevented because of charge screening by the salt. Upon increasing the temperature, both types of micelles display a cloud point temperature (Tcp), despite the small thermoresponsive blocks, and aggregate into hydrogels. These hydrogels consist of a complexed polyelectrolyte matrix with microphase separated PNIPAM domains. Controlling the morphology and aggregation of temperature sensitive polyelectrolytes can be an important tool for drug delivery systems, or the application and hardening of underwater glues.

Delivery of lipid fractions in the lower small intestine can induce feelings of satiety, but is only possible when lipids escape the highly efficient lipolysis and adsorption in the upper gastrointestinal (GI) tract. Our objective was to gain insight in the stability of multilayered interfaces in simulated GI conditions, and their suitability for intestinal delivery of undigested lipids. Oil-in-water emulsions (d32 ∼ 5–30 μm; one- to five-layered interfaces) were produced by sequentially adsorbing biopolymers with opposite charges at pH 3.0: whey protein isolate (WPI) (cationic), pectin (anionic), chitosan (cationic). Corresponding multilayered structures were characterized using reflectometry. Influence of layer composition and thickness on its protectiveness against lipolysis of emulsions was studied in simulated GI conditions. Multilayered WPI/pectin emulsions had an improved physical stability compared to WPI-stabilized emulsions, during both storage and in vitro gastric incubation, whereas chitosan-containing emulsions were physically unstable. Reflectometry and CLSM results showed that a greater number of layers increased the adsorbed amount, forming a mesoscopically heterogeneous structure. Under simulated intestinal conditions, however, outer layers instantaneously destabilized. Accordingly, similar initial lipolysis rates were recorded for all emulsions. Yet, compared to only WPI the final extent of lipolysis was lowered by addition of a second and a third layer under mild in vitro conditions. This moderate protective effect disappeared when harsher digestive conditions were applied. From this work, it became clear why multilayered interfaces (initially built under acidic pH) can improve gastric stability of emulsions, but are prone to disintegration under intestinal conditions. This knowledge is important for designing food systems that control release of lipolytic products in targeted locations of the GI tract; the emulsions reported her

To obtain insight in translocation of nanoparticles across the placental barrier, translocation was studied for one positively and two negatively charged polystyrene nanoparticles (PS-NPs) of similar size in an in vitro model. The model consisted of BeWo b30 cells, derived from a human choriocarcinoma grown on a transwell insert forming a cell layer that separates an apical from a basolateral compartment. PS-NPs were characterized with respect to size, surface charge, morphology and protein corona. Translocation of PS-NPs was not related to PS-NP charge. Two PS-NPs were translocated across the BeWo transwell model to a lower extent than amoxicillin, a model compound known to be translocated over the placental barrier to only a limited extent, whereas one PS-NP showed a slightly higher translocation. Studies on the effect of transporter inhibitors on the translocation of the PS-NPs indicated that their translocation was not mediated by known transporters and mainly dependent on passive diffusion. It is concluded that the BeWo b30 model can be used as an efficient method to get an initial qualitative impression about the capacity of NPs to translocate across the placental barrier and set priorities in further in vivo studies on translocation of NPs to the fetus.

Herein, we present a facile strategy to controllably build up dendrimicelles by self-assembly of anionic PAMAM dendrimers with cationic–neutral diblock copolymers. We present a systematic study incorporating a full decade (0–9) of dendrimer generations, tracing the gradual variation from aggregates (G0 and G1) to self-assembled micelles (G2–G8), and an unidendrimer micelle structure (G9) by different scattering techniques (light and X-ray). The formed micelles (G2–G9) are spherical in shape with a hydrodynamic radius of about 25 nm. Interestingly, the micellar size, structure and number of incorporated block copolymers are independent of the dendrimer generation (for G2 to G9), while the aggregation number of the dendrimers decreases from 108 to 1, and the stability of the micelles increases upon an increase in the dendrimer generation. Moreover, the micelles with lower generation dendrimers transform from spherical into worm-like structures upon an increase in the positive charge fraction (excess polymers) or ionic strength, while micelles with higher generation dendrimers do not show such a transition. This differential behavior is in-line with a change from a flexible configuration into rigid globular nanoparticles with increasing dendrimer generation. The reported systematic investigation of dendrimicelles comprising a full decade of dendrimer generations provides the basis for versatile strategies focused on building up new (multi)functional materials, e.g. by packing multiple types of dendrimers with different functional groups or encapsulated cargos controllably within one micelle.

Stress relaxation in crystalline solids is mediated by the formation and diffusion of defects. Although it is well established how externally generated stresses relax, through the proliferation and motion of dislocations in the lattice, it remains relatively unknown how crystals cope with internal stresses. We investigate, both experimentally and in simulations, how highly localized stresses relax in 2D soft colloidal crystals. When a single particle is actively excited, by means of optical tweezing, a rich variety of highly collective stress relaxation mechanisms results. These relaxation processes manifest in the form of open strings of cooperatively moving particles through the motion of dissociated vacancy-interstitial pairs, and closed loops of mobile particles, which either result from cooperative rotations in transiently generated circular grain boundaries or through the closure of an open string by annihilation of a vacancy-interstitial pair. Surprisingly, we find that the same collective events occur in crystals that are excited by thermal fluctuations alone; a large thermal agitation inside the crystal lattice can trigger the irreversible displacements of hundreds of particles. Our results illustrate how local stresses can induce large-scale cooperative dynamics in 2D soft colloidal crystals and shed light on the stabilization mechanisms in ultrasoft crystals.

Item does not contain fulltext, Effective vaccines consist of 2 components: immunodominant antigens and effective adjuvants. Whereas it has been demonstrated that targeted delivery of antigens to dendritic cells (DCs) improves vaccine efficacy, we report here that co-targeting of TLR ligands (TLRLs) to DCs strongly enhances adjuvanticity and immunity. We encapsulated ligands for intracellular TLRs within biodegradable nanoparticles coated with Abs recognizing DC-specific receptors. Targeted delivery of TLRLs to human DCs enhanced the maturation and production of immune stimulatory cytokines and the Ag-specific activation of naive CD8(+) T cells. In vivo studies demonstrated that nanoparticles carrying Ag induced cytotoxic T-lymphocyte responses at 100-fold lower adjuvant dose when TLRLs were co-encapsulated instead of administered in soluble form. Moreover, the efficacy of these targeted TLRLs reduced the serum cytokine storm and related toxicity that is associated with administration of soluble TLRLs. We conclude that the targeted delivery of adjuvants may improve the efficacy and safety of DC-based vaccines.

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