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Amorphous solid dispersions (ASD) are known to enhance the absorption of poorly water-soluble drugs. In this work we synthesise well-defined Polyvinylpyrrolidone (PVP) to establish the impact of dispersity and chain-end functionality on the physical properties of Curcumin (CUR)/PVP ASD. Thermodynamic characterisation of synthesised PVP emphasises a strong effect of the dispersity on the glass transition temperature (Tg), 50 °C higher for synthesised PVP than for commercial PVP K12 of same molar mass. This increase of Tg affects the thermodynamic properties of CUR/PVP ASD successfully formulated up to 70 wt% of CUR by milling or solvent evaporation. The evolution of both the Tg and CUR solubility values versus CUR content points out the development of fairly strong CUR-PVP interactions that strengthen the antiplasticising effect of PVP on the Tg of ASD. However, for ASD formulated with commercial PVP this effect is counterbalanced at low CUR content by a plasticising effect due to the shortest PVP chains. Moreover, the overlay of the phase and state diagrams highlights the strong impact of the polymer dispersity on the stability of CUR/PVP ASD. ASD formulated with low dispersity PVP are stable on larger temperature and concentration ranges than those formulated with PVP K12.

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Compartmentalization and binding-triggered conformational change regulate many metabolic processes in living matter. Here, we have synergistically combined these two biorelevant processes to tune the Diels-Alder (DA) reactivity of a synthetic self-complexing host-guest molecular switch CBPQT4+ -Fu, consisting of an electron-rich furan unit covalently attached to the electron-deficient cyclobis(paraquat-p-phenylene) tetrachloride (CBPQT4+ , 4Cl- ) host. This design allows CBPQT4+ -Fu to efficiently compartmentalize the furan ring inside its host cavity in water, thereby protecting it from the DA reaction with maleimide. Remarkably, the self-complexed CBPQT4+ -Fu can undergo a conformational change through intramolecular decomplexation upon the addition of a stronger binding molecular naphthalene derivative as a competitive guest, triggering the DA reaction upon addition of a chemical regulator. Remarkably, connecting the guest to a thermoresponsive lower critical solution temperature (LCST) copolymer regulator controls the DA reaction on command upon heating and cooling the reaction media beyond and below the cloud point temperature of the copolymer, representing a rare example of decreased reactivity upon increasing temperature. Altogether, this work opens up new avenues towards combined topological and supramolecular control over reactivity in synthetic constructs, enabling control over reactivity through molecular regulators or even mild temperature variations.

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Despite many efforts devoted toward the design of covalent organic frameworks (COFs) at the framework level by selecting the building blocks, their organization in the nano to meso regimes is often neglected. Moreover, the importance of processability for their applications has recently emerged and the synthesis of COF nanostructures without agglomeration is still a challenge. Herein, the first example of hybrid COF-polymer particles for which polymers are used to manipulate the 2D COF growth along a specific direction is reported. The study examines how the nature, chain-end functionality, and molar mass of the polymer influence the shaping of hybrid 2D boronate ester-linked COF-polymer particles. Catechol-poly(N-butyl acrylate) leads to the self-assembly of crystallites into quasi-spherical structures while catechol-poly(N-isopropylacrylamide) mediates the synthesis of raspberry-like COF-polymer particles with radial grain orientation. Scanning and transmission electron microscopies (SEM and TEM) and 4D-STEM-ACOM (automated crystal orientation mapping) highlight the single-crystal character of these domains with one plane family throughout the particles. Interestingly, the presence of PNIPAm on the particle surface allows their drying without co-crystallization and enables their resuspension. Kinetic investigations show that catechol-PnBuA acts as a modulator and catechol-PNIPAm induces a template effect, introducing supramolecular self-assembly properties into particles to create new morphologies with higher structural complexity, beyond the framework level.

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3D/4D printing is enabling transformative advances in device manufacturing and medicine but remains limited by the lack of printable resorbable materials with advanced properties and functions. Herein, we report the rapid and precise 4D printing of shape-memory scaffolds based on poly(propylene fumarate) (PPF) star polymers. Scaffolds with tunable and distinguishable properties can be produced with identical polymer formulation and stoichiometry. The resulting scaffold glass transition temperatures and Young's moduli increase with the postcuring time. Significantly, both the extent and rate of shape recovery following compression can be tuned by varying the strut design, the postcuring step duration, and/or the temperature applied for the recovery step. Finally, accelerated degradation studies confirmed the resorbability of the PPF star polymer gyroid scaffolds.

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Complex three-dimensional (3D) pore geometries, useful for tissue engineering scaffolds, can be fabricated via photo-crosslinking of resorbable poly(propylene fumarate) (PPF) resins using stereolithography (SLA) and/or continuous digital light processing (cDLP) methods. Physico-chemical parameters inherent to 3D printable resin design, include viscosity, polymer concentration, degree of polymerization, and resin printing temperature. We report here on our study of these parameters and their influence the cDLP 3D printing process and the resulting mechanical properties. A series of PPF oligomers were synthesized by the ring-opening copolymerization (ROCOP) of maleic anhydride and propylene oxide followed by a base-catalyzed isomerization. The resin viscosities were measured as a function of number-average molecular mass ([Formula: see text]) of the PPF oligomers (1.1, 1.7 and 2.0 kDa), concentrations of PPF in the reactive diluent diethyl fumarate (DEF) (50 and 75 wt %) and resin temperature (25 to 55 °C). The zero-shear viscosity (η0) of the resins was found to be temperature-dependent and follow a linear Arrhenius relationship. Tensile tests demonstrated mechanical properties within the range of trabecular bone, with the ultimate strength at break above 15 MPa and elastic moduli between 178 and 199 MPa.

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The synthesis and original thermoresponsive behavior of hybrid diblock copolypeptides composed of synthetic and recombinant polypeptides are herein reported. A thermoresponsive recombinant elastin-like polypeptide was used as a macroinitiator to synthesize a range of poly( l-glutamic acid)- block-elastin-like polypeptide (PGlu- b-ELP) diblock copolypeptides with variable PGlu block lengths. Their temperature-triggered self-assembly in water and in phosphate-buffered saline (PBS) was investigated at the macroscopic scale using complementary techniques such as turbidimetry, dynamic and static light scattering, small-angle neutron scattering, and at the molecular scale by 1H NMR and circular dichroism (CD). In deionized water, PGlu- b-ELP copolypeptides showed one transition from free soluble chains below the transition temperature ( Tt) of the ELP block to macroscopic aggregates above the Tt. In contrast, in PBS, four successive regimes were observed upon increasing temperature: below the Tt, copolypeptides were soluble, above the Tt, large aggregates appeared and fell apart into discrete and defined spherical nanoparticles at a temperature named critical micellization temperature (CMT), before finally reaching an equilibrium. During the last regime, neutron scattering experiments revealed that the micelle-like structures underwent a densification step and expelled water from their core. In addition, 1H NMR and CD experiments revealed, in deionized water, the formation of type II ß-turns into the ELP block upon temperature increase. These ß-turns are known to participate in the intrinsic thermoresponsive behavior of the ELPs. In contrast, in PBS, circular dichroism measurements showed an attenuation of folded structure during the self-assembly phase, leading to less cohesive aggregates able to reorganize into nanoparticles at the CMT.

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The precision synthesis and self-assembly of amphiphilic copolypeptides containing a recombinant elastin-like polypeptide (ELP) block used as a macroinitiator for the ring opening polymerization (ROP) of γ-benzyl-l-glutamate (γ-BLG NCA) are herein presented. The molecular weight of the resulting PBLG-b-ELP block copolypeptides was precisely controlled without the use of complex initiator or demanding experimental setup. Diblock copolypeptides were obtained with an excellent control of the polymerization highlighted by the dispersity below 1.04. These amphiphilic hybrid synthetic/recombinant copolypeptides were self-assembled in water and the nanoparticles obtained were characterized by a combination of dynamic light scattering and electron microscopy. A variety of morphologies, namely polymersomes, inter-connected worm-like micelles and spherical micelles, were evidenced depending on the hydrophilic ratio of the diblocks as well as the self-assembly procedure.

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Stealth nanocarriers are a promising technology for the treatment of diseases. However, the preparation and characterization of well-defined soft nanoparticulate systems remain challenging. Here we describe a platform of amphiphilic graft copolymers leading to nanoparticles with multiple morphologies and the role of the hydrophilic backbone in their interaction with a model protein. The amphiphilic graft copolymers platform was composed of hydrophilic backbone poly(2-methyl-2-oxazoline-co-2-pentyl-2-oxazoline) (P(MeOx-co-PentOx)), prepared via cationic ring-opening polymerization. Hydrophobic poly(d,l-lactide) (PLA) chains were grafted on the backbone via Huisgen 1,3-dipolar cycloaddition. The "click" copper-catalyzed cycloaddition reactions of azides with alkynes (CuAAC) were successfully carried out, and a series of amphiphilic copolymers were prepared containing a backbone with a number-average molecular weight of 14.2 × 103 g mol-1 and different hydrophobic PLA grafts with various molecular weights (2.8 × 103-12.4 × 103 g mol-1). These original architectures of copolymers, when nanoprecipitated in water, the backbone-selective solvent, allowed us to obtain various structures of nanoparticles with a hydrodynamic diameter in the range of 65-99 nm. More interestingly, a plurality of morphologies going from unilamellar, multilamellar, and large compound vesicles to core-shell nanoparticles and depending on the PLA molecular weights were evidenced by combining cryo-transmission electron microscopy (cryo-TEM) and small-angle neutron scattering (SANS) studies. A first evaluation of their stealthiness by studying the stability and the interaction of these nano-objects with a model protein revealed the role played by the P(MeOx-co-PentOx) in these interactions, demonstrating the utility of this amphiphilic graft copolymers platform with well-defined architectures for the design of nanocarriers in drug delivery applications.

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We present a straightforward method to prepare amphiphilic graft copolymers consisting of hydrophobic poly(3-hydroxyalkanoates) (PHAs) backbone and hydrophilic α-amino-ω-methoxy poly(oxyethylene-co-oxypropylene) (Jeffamine®) units. Poly(3-hydroxyoctanoate)-co-(3-hydroxyundecenoate) (PHOU) was first methanolyzed to obtain the desired molar mass. The amino end groups of Jeffamine were converted into thiol by a reaction with N-acetylhomocysteine thiolactone and subsequently photografted. This "one-pot" functionalization prevents from arduous and time-consuming functionalization of the hydrophilic precursor or tedious modifications of PHAs, thus simplifying the process. The amphiphilic nature of modified PHAs leads to water-soluble copolymers exhibiting thermoresponsive behavior.

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