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Soft nanoparticles are interesting materials due to their size, deformability, and ability to host guest molecules. Surface properties play an essential role in determining the fate of the particles in biological medium, and coating of the nanoparticles (and polymers) with carbohydrates has been found to be an efficient strategy for increasing their biocompatibility and fine-tuning other important properties such as aqueous solubility. In this work, soft nanogels of poly( N -vinylcaprolactam), PNVCL, were surface-functionalized with different glucose and maltose ligands, and the colloidal properties of the gels were analyzed. The PNVCL nanogels were first prepared via semibatch precipitation polymerization, where a comonomer, propargyl acrylate (PA), was added after preparticle formation. The aim was to synthesize "clickable" nanogels with alkyne groups on their surfaces. The nanogels were then functionalized with two separate azido-glucosides and azido-maltosides (containing different linkers) through a copper-catalyzed azide-alkyne cycloaddition (CuAAc) click reaction. The glucose and maltose bearing nanogels were thermoresponsive and shrank upon heating. Compared to the PNVCL-PA nanogel, the carbohydrate bearing ones were larger, more hydrophilic, had volume phase transitions at higher temperatures, and were more stable against salt-induced precipitation. In addition to investigating the colloidal properties of the nanogels, the carbohydrate recognition was addressed by studying the interactions with a model lectin, concanavalin A (Con A). The binding efficiency was not affected by the temperature, which indicates that the carbohydrate moieties are located on the gel surfaces, and are capable of interacting with other biomolecules independent of temperature. Thus, the synthesis produces nanogels, which have surface functions capable of biorelevant interactions and a thermoresponsive structure. These types of particles can be used for drug delivery.

Treatment of retinal diseases currently demands frequent intravitreal injections due to rapid clearance of the therapeutics. The use of high molecular weight polymers can extend the residence time in the vitreous and prolong the injection intervals. This study reports a water soluble graft copolymer as a potential vehicle for sustained intravitreal drug delivery. The copolymer features a high molecular weight hyaluronic acid (HA) backbone and poly(glyceryl glycerol) (PGG) side chains attached via hydrolysable ester linkers. PGG, a polyether with 1,2-diol groups in every repeating unit available for conjugation, serves as a detachable carrier. The influence of synthesis conditions and incubation in physiological media on the molecular weight of HA is studied. The cleavage of the PGG grafts from the HA backbone is quantified and polymer-from-polymer release kinetics are determined. The biocompatibility of the materials is tested in different cell cultures., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Details of the phase separation of the poly(N-vinylcaprolactam) (PVCL) homopolymers and block copolymers of PVCL and poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) were studied in aqueous buffer solutions. Phase separation occurred at either one or two temperatures depending on pH. The lower critical solution temperature of PVCL can be fine-tuned by varying the molecular weight of the block, whereas the phase separation temperature of the PDMAEMA block is strongly dependent on pH. The enthalpies of the collapse of the PVCL homopolymer and PVCL-b-PDMAEMA block copolymers were measured and show that the blocks phase separate independently upon heating. PVCL is known to bind amphiphilic cations, and correspondingly, according to light scattering, the block copolymers dissolve as single molecules but also form aggregates at room temperature. At temperatures above the cloud points of both blocks, only homogeneous large aggregates were observed. Zeta potential measurements confirmed that, upon heating, PDMAEMA blocks turn out from the collapsed PVCL globule toward the aqueous phase.

Aqueous solution and water-air interfacial properties of associative thermally responsive A-B-A stereoblock poly(N-isopropylacryl amide), PNIPAM, polymers were studied and compared to atactic PNIPAM. The A-B-A polymers consist of atactic PNIPAM as a hydrophilic block (either A or B) and a water-insoluble block of isotactic PNIPAM. The surface tensions of aqueous PNIPAM solutions were measured as a function of both temperature and concentration. The isotactic blocks did not have an effect on the surface activity of the solutions. Rheological measurements on the water-air interface showed that the aggregated PNIPAMs containing isotactic blocks increased the elasticity of the surface significantly as compared to the atactic reference upon heating. Two fluorescence probes, pyrene and (4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran (4HP), added to the aqueous polymer solutions were concluded to reside in surroundings with lower polarity and increased microviscosity in cases when the polymers contained isotactic blocks, as compared to ordinary atactic polymers.

The use of additives in crystallization of pharmaceuticals is known to influence the particulate properties critically affecting downstream processing and the final product performance. Desired functionality can be build into these materials, e.g. via optimized synthesis of a polymeric additive. One such additive is the thermosensitive polymer poly(N-isopropyl acrylamide) (PNIPAM). The use of PNIPAM as a crystallization additive provides a possibility to affect viscosity at separation temperatures and nucleation and growth rates at higher temperatures. In this study, novel PNIPAM derivatives consisting of both isotactic-rich and atactic blocks were used as additives in evaporative crystallization of a model compound, nitrofurantoin (NF). Special attention was paid to possible interactions between NF and PNIPAM and the aggregation state of PNIPAM as a function of temperature and solvent composition. Optical light microscopy and Raman and FTIR spectroscopy were used to investigate the structure of the NF crystals and possible interaction with PNIPAM. A drastic change in the growth mechanism of nitrofurantoin crystals as monohydrate form II (NFMH-II) was observed in the presence of PNIPAM; the morphology of crystals changed from needle to dendritic shape. Additionally, the amphiphilic nature of PNIPAM increased the solubility of nitrofurantoin in water. PNIPAMs with varying molecular weights and stereoregularities resulted in similar changes in the crystal habit of the drug regardless of whether the polymer was aggregated or not. However, with increased additive concentration slower nucleation and growth rates of the crystals were observed. Heating of the crystallization medium resulted in phase separation of the PNIPAM. The phase separation had an influence on the achieved crystal morphology resulting in fewer, visually larger and more irregular dendritic crystals. No proof of hydrogen bond formation between PNIPAM and NF was observed, and the suggested mechanism for the observed dendritic morphology is related to the steric hindrance phenomenon. PNIPAM can be used as a crystallization additive with an obvious effect on the growth of NF crystals.

Highly elastic and robust nanocomposite hydrogels based on N-isopropylacrylamide (NIPAM) and cationic (3-acrylamidopropyl) trimethylammonium chloride (AMPTMA) were synthesized by photopolymerization. Nanoscopic clay, laponite XLS, was added in the gels during the synthesis. The effect of a hydrophobic salt, lithium bis(trifluoromethane) sulfonimide (LiNTf2), and clay content on the viscoelastic properties, swelling ratio, and stiffness of the nanocomposite hydrogels were investigated as a function of temperature. Synthetic clay served as a multifunctional cross-linker, producing hydrogels with enhanced elastic properties. Anionic NTf2 binds to the cationic comonomer units and significantly affected the viscoelasticity and thermal properties. DSC measurements showed that the volume phase transition temperature and its enthalpy changed with the clay content and with introducing the cationic comonomer (AMPTMA) in the PNIPAM network. With the addition of either laponite XLS or the comonomer and 5 mM solution of LiNTf2, a fourfold and fivefold increase in elastic modulus was obtained, respectively, compared to that of the homopolymer PNIPAM hydrogel. With increasing the temperature from 20 to 45°C for the copolymer gel with 10% AMPTMA in 5 mM LiNTf2, the elastic modulus grew 15 times larger. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the usability of poly( N-isopropyl acrylamide) (PNIPAM) as an additive for crystallization of a model drug, nitrofurantoin (NF), and utilizing the thermoresponsivity of the polymer to enable control of the viscosity during the crystallization process. Crystallization of NF in the presence of PNIPAM resulted in dendritic crystal growth and the originally observed growth of needle-shaped crystals was prohibited. The effect of acetone, a cosolvent used for the crystallization, on thermosensitivity of PNIPAM was studied and the properties of atactic PNIPAM and triblock PNIPAM polymers containing atactic and isotactic rich blocks were compared. The investigated PNIPAMs were all soluble in the acetone-water mixtures leading to phase separation at lower temperatures with increasing acetone content, up to approximately 50 vol% (0.20 mol fraction). At higher acetone contents no phase separation was observed on heating. The presence of acetone altered the viscosity of the solutions prior to the phase separation depending on the polymer architecture. The PNIPAM polymers induced smaller and potentially more easily processable crystals, however, the viscosity increase in the presence of acetone occurred only 1-3 °C prior to phase separation complicating the practical use of this approach. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to investigate the rheological properties, molecular mobility and crystallization tendency of pure citric acid and paracetamol or blends of them. Amorphous samples were produced by ethanol-evaporation or by melt-quenching. Enthalpy recovery, glass fragility and heat capacity were determined by differential scanning calorimetry (DSC). Other physical characterization methods were rheology and the crystallization tendency using X-ray powder diffraction (XRPD) and DSC. All the samples behaved as Newtonian liquids and they were fragile glasses. The 50/50 (w/w,%) blend had good physical stability upon consecutive shearing regardless of the preparation method. All the samples were stable for at least one year in dry conditions at −20°C. The melt-produced blends containing 25% or 50% paracetamol were stable at least two years in dry ambient conditions. The good physical stability at ambient temperature cannot be explained by molecular mobility because molecular mobility of the model material is less than 100s in ambient conditions. Thus other factors, such as the thermodynamic and crystallization driving forces or formation of degradation products, must determine the physical stability of the blends. The composition and processing method have an impact on the physical stability of the sample. [Copyright &y& Elsevier]

Abstract: Rheological properties of aqueous solutions and hydrogels formed by an amphiphilic star block copolymer, poly(acrylic acid)-block-polystyrene (PAA54-b-PS6)4, were investigated as a function of the polymer concentration (C p), temperature, and added salt concentration. The water-soluble polymer synthesised by atom transfer radical polymerization (ATRP) was found to form hydrogels at room temperature at polymer concentrations, C p, over 22g/L due to the interpolymer hydrophobic association of the PS blocks. Increasing C p leads to stronger elastic networks at room temperature that show a gel-to-solution transition with increasing temperature. Increase of ionic strength decreases the moduli compared with the pure hydrogel but did not affect the gel–sol transition temperature significantly. Small-angle X-ray experiments showed two distinct scattering correlation peaks for samples above the gelling C p, which indicates the aggregates formed due to hydrophobic association. Upon heating the intensity of the scattering correlation peaks was found to decrease indicating the loss of the network structure due to thermal motion. [Copyright &y& Elsevier]

Abstract: Self-assembling properties of an amphiphilic star block copolymer, 4-arm (PMMA-b-PAA)4 with poly(methyl methacrylate) core and poly(acrylic acid) shell, have been investigated in aqueous solutions. The stars have been observed to aggregate in a complex manner in aqueous solutions, depending on the presence or absence of salt. Screening of the electrostatic repulsion between the polyelectrolyte blocks by adding salt triggers the formation of worm-like micelles. The presence of worm-like micelles in saline solutions was revealed by Kratky analysis of the light scattering data. The coexistence of different micellar morphologies was visualized by direct imaging by cryoTEM. Due to the balance between the electrostatic and hydrophobic interactions semidilute solutions show interesting rheological properties. Shear thinning behavior of salt-free solutions and their time-dependent gelation have been observed, thus indicating the strong tendency of the polymers to aggregate. [Copyright &y& Elsevier]

Abstract: The colloidal stability and characteristics of particles formed by homopolymers of poly(N-vinyl caprolactam), poly(N-isopropyl acrylamide) and poly(vinyl methyl ether) in dilute aqueous solutions above the lower critical solution temperature, LCST, was followed by means of dynamic and static light scattering. Depending on the solution concentration, the homopolymers precipitate or form stable dispersions of monodisperse spherical particles. To obtain colloidally stable aggregates, also called mesoglobules, no stabilising agent was added. The stability of the mesoglobules upon time and dilution at temperatures above the LCST suggests that the particle surfaces possess a hydrophilic character. The size of the formed particles depends on the concentration and the heating rate of the solutions. However, internal structure and shape of mesoglobules are affected neither by the way, how the mesoglobules were prepared, nor by molar mass of individual macromolecules. Mesoglobules of PNIPAM obey the M∝R 2.7 scaling law. Origin of stability of the dispersions vs. expected precipitation is discussed. [Copyright &y& Elsevier]