Concentrated Solutions Of Poly Research Articles

In Situ Forming Injectable Thermoresponsive Hydrogels for Controlled Delivery of Biomacromolecules.

Due to their relatively large molecular sizes and delicate nature, biologic drugs such as peptides, proteins, and antibodies often require high and repeated dosing, which can cause undesired side effects and physical discomfort in patients and render many therapies inordinately expensive. To enhance the efficacy of biologic drugs, they could be encapsulated into polymeric hydrogel formulations to preserve their stability and help tune their release in the body to their most favorable profile of action for a given therapy. In this study, a series of injectable, thermoresponsive hydrogel formulations were evaluated as controlled delivery systems for various peptides and proteins, including insulin, Merck proprietary peptides (glucagon-like peptide analogue and modified insulin analogue), bovine serum albumin, and immunoglobulin G. These hydrogels were prepared using concentrated solutions of poly(lactide-co-glycolide)–block-poly(ethylene glycol)–block-poly(lactide-co-glycolide) (PLGA–PEG–PLGA), which can undergo temperature-induced sol–gel transitions and spontaneously solidify into hydrogels near the body temperature, serving as an in situ depot for sustained drug release. The thermoresponsiveness and gelation properties of these triblock copolymers were characterized by dynamic light scattering (DLS) and oscillatory rheology, respectively. The impact of different hydrogel-forming polymers on release kinetics was systematically investigated based on their hydrophobicity (LA/GA ratios), polymer concentrations (20, 25, and 30%), and phase stability. These hydrogels were able to release active peptides and proteins in a controlled manner from 4 to 35 days, depending on the polymer concentration, solubility nature, and molecular sizes of the cargoes. Biophysical studies via size exclusion chromatography (SEC) and circular dichroism (CD) indicated that the encapsulation and release did not adversely affect the protein conformation and stability. Finally, a selected PLGA–PEG–PLGA hydrogel system was further investigated by the encapsulation of a therapeutic glucagon-like peptide analogue and a modified insulin peptide analogue in diabetic mouse and minipig models for studies of glucose-lowering efficacy and pharmacokinetics, where superior sustained peptide release profiles and long-lasting glucose-lowering effects were observed in vivo without any significant tolerability issues compared to peptide solution controls. These results suggest the promise of developing injectable thermoresponsive hydrogel formulations for the tunable release of protein therapeutics to improve patient’s comfort, convenience, and compliance.

Co-nonsolvency in concentrated aqueous solutions of PNIPAM: effect of methanol on the collective and the chain dynamics.

The polymer dynamics in concentrated solutions of poly(N-isopropyl acrylamide) (PNIPAM) in D2O/CD3OD mixtures is investigated in the one-phase region. Two polymer concentrations (9 and 25 wt%) and CD3OD contents in the solvent mixture of 0, 10 and 15 vol% are chosen. Temperature-resolved dynamic light scattering (DLS) reveals the collective dynamics. Two modes are observed, namely the fast relaxation of polymer segments within the blobs and the slow collective relaxation of the blobs. As the cloud point is approached, the correlation length related to the fast mode increases with CD3OD content. It features critical scaling behavior, which is consistent with mean-field behavior for the 9 wt% PNIPAM solution in pure D2O and with 3D Ising behavior for all other solutions. While the slow mode is not very strong in the 9 wt% PNIPAM solution in pure D2O, it is significantly more prominent as CD3OD is added and at all CD3OD contents in the 25 wt% solution, which may be attributed to enhanced interaction between the polymers. Neutron spin-echo spectroscopy (NSE) reveals a decay in the intermediate structure factor which indicates a diffusive process. For the polymer concentration of 9 wt%, the diffusion coefficients from NSE are similar to the ones from the fast relaxation observed in DLS. In contrast, they are significantly lower for the solutions having a polymer concentration of 25 wt%, which is attributed to the influence of the dominant large-scale dynamic heterogeneities. To summarize, addition of cosolvent leads to enhanced large-scale heterogeneities, which are reflected in the dynamic behavior at small length scales.

Use of partial molar volume for determining conformations of macromolecules in a solution

A formula was derived for determining the partial molar volume (PMO) of solute at various concentrations and on this basis a method was developed for determining the PMO at infinite dilution. The partial molar volumes of the homologous series of poly(ethylene glycol) with molecular masses 400, 1000, 1500, 2000, 4000, 20000 in aqueous solutions at infinite dilution were determined. Analysis of the calculated and experimental PMO showed that poly(ethylene glycol) molecules exist in dilute solutions in the conformations of elongated helices. In addition, the high-molecular polyethylene glycol molecules include the areas of statistical chaos, which leads to sites unavailable for the solvent molecules. Based on literature data were revealed the values of PMO for highly concentrated solutions of poly(ethylene glycol) PEG 400, PEG 4000, and PEG 6000. Effect of concentration on the structure of PEG solutions was demonstrated. We found that in the temperature range 25–40°C the conformational transitions were not observed.

Role of Polymer Segment–Particle Surface Interactions in Controlling Nanoparticle Dispersions in Concentrated Polymer Solutions

The microstructure of particles suspended in concentrated polymer solutions is examined with small-angle X-ray scattering and small-angle neutron scattering. Of interest are changes to long wavelength particle density fluctuations in ternary mixtures of silica nanoparticles suspended in concentrated solutions of poly(ethylene glycol). The results are understood in terms of application of the pseudo-two-component polymer reference interaction site model (PRISM) theory modified to account for solvent addition via effective contact strength of interfacial attraction, ε(pc), in an implicit manner. The combined experimental-theoretical study emphasizes the complex interactions between solvent, polymer, and particle surface that control particle miscibility but also demonstrate that these factors can all be understood in terms of variations of ε(pc).

Tuning Size and Sensing Properties in Colloidal Gold Nanostars

Gold nanostars are multibranched nanoparticles with sharp tips, which display extremely interesting plasmonic properties but require optimization. We present a systematic investigation of the influence of different parameters on the size, morphology, and monodispersity of Au nanostars obtained via seeded growth in concentrated solutions of poly(vinylpyrrolidone) in N,N-dimethylformamide. Controlled prereduction of Au(3+) to Au(+) was found to influence monodispersity (narrower plasmon bands), while the [HAuCl(4)]/[seed] molar ratio significantly affects the morphology and tip plasmon resonance frequency. We also varied the size of the seeds (2-30 nm) and found a clear influence on the final nanostar dimensions as well as on the number of spikes, while synthesis temperature notably affects the morphology of the particles, with more rounded morphologies formed above 60 °C. This rounding effect allowed us to confirm the importance of sharp tips on the optical enhancing behavior of these nanoparticles in surface-enhanced raman scattering (SERS). Additionally, the sensitivity toward changes in the local refractive index was found to increase for larger nanostars, though lower figure of merit (FOM) values were obtained because of the larger polydispersity.

High-yield synthesis and optical response of gold nanostars

Multipod Au nanoparticles (nanostars) with single crystalline tipswere synthesized in extremely high yield through the reduction ofHAuCl4 in a concentrated solution of poly(vinylpyrrolidone) (PVP) inN,N-dimethylformamide (DMF), in the presence of preformed Au nanoparticle seeds, but withno need for external energy sources. Nanostar dispersions display a well-definedoptical response, which was found (through theoretical modeling) to comprise amain mode confined within the tips and a secondary mode confined in the centralbody. Calculations of the surface enhanced Raman scattering (SERS) responseadditionally show that this morphology will be relevant for sensing applications.

Dielectric study of concentration fluctuations in concentrated polymer solutions

Dielectric relaxation of the segmental mode in concentrated solutions of poly(vinyl acetate) (PVAc) in toluene (Tol) and in 1-methylnaphthalene (MN) and those of poly(vinyl octanoate) (PVOc) in Tol were studied. It was found that the distributions of relaxation times in concentrated solutions were much broader than those in dilute solution and in the undiluted bulk polymer. The broad spectra were ascribed to local heterogeneities. The half width Λ increased with decreasing temperature and this behavior was explained by assuming that Λ is proportional to the amplitude of the local concentration fluctuation Δφ times the slope of the φ dependence curve of the average relaxation time τ. This assumption leads to a linear relationship between Λ and Δφ/( T− T 0) 2 where T 0 is the Vogel critical temperature. Using this relation, we attempted to estimate Δφ.

Characterization of Polyaniline and Poly(m-toluidine)-based Nanoparticles of Ultranarrow Particle Size Distribution

The oxidative polymerization of aniline or m-toluidine, carried out in concentrated solutions of poly(vinyl alcohol-co-acetate) (PVA), was used to prepare colloidal composite particles of polyaniline-PVA or poly(m-toluidine)-PVA of ultranarrow particle size distribution and of controlled average particle size. The particle size distributions were measured by quasi-elastic light scattering in diluted polymerization products. Such a measurement can be influenced by undestroyed PVA aggregates formed in the initial solution. The aim of this work was to determine conditions under which the true particle size distribution of the composite particles can be measured or, at least, estimate the degree such a determination is influenced by PVA aggregates not incorporated into the composite particles. Quasi-elastic light scattering measurements of the diluted polymerization products were carried out under various experimental conditions. The composite particles were separated from the PVA solution by centrifugation and redispersed in water. The size of the redispersed composite particles and of the PVA aggregates in the supernatant solution was measured again by quasi-elastic light scattering. Scanning electron microscopy showed the spherical shape of the synthesized composite particles and confirmed their ultranǎrrow size distribution.

Simultaneous optical observation of anisotropic texture for a concentrated solution of poly(γ-benzyl- l -glutamate) under transient stress response in shear flow

Simultaneous optical observation of anisotropic texture was performed under transient stress response in shear flow for a concentrated solution of poly(γ-benzyl-l-glutamate) (PBLG). Transient stress of the PBLG solution immediately after the onset of the shear flow showed a remarkable stress overshoot and damping oscillation behavior, followed by a steady state. On the other hand, simultaneous observation of the polarized optical microscopy showed the remarkable distortion of the banded texture immediately after the onset of the shear flow and the periodical changes in the retardation followed by a steady texture of the PBLG solution. The remarkable stress overshoot and the damping oscillation are closely related to the distortion of the banded texture and to the changes in the orientation of the rod-like molecules of the PBLG, respectively.

Perspective: Comments on “Rheology of concentrated solutions of poly(γ-benzyl-glutamate),” by Gabor Kiss and Roger S. Porter,J. Polym. Sci., Polym. Symp., 65, 193 (1978)

Perspective: Comments on “Rheology of concentrated solutions of poly(γ-benzyl-glutamate),” by Gabor Kiss and Roger S. Porter,J. Polym. Sci., Polym. Symp., 65, 193 (1978)

Local and global motions in concentrated solutions of poly(methyl methacrylate)/bis(2-ethylhexyl phthalate)

Photon correlation spectra (PCS) of the polarized and depolarized component of the scattered light have been recorded in concentrated solutions of low molecular weight poly(methylmethacrylate) (PMMA) in bis(2 ethylhexyl phthalate) (DOP), in the temperature range 250–360 K. At high temperatures, T, above, the glass transition temperature, T ng, PCS probes the concentration fluctuations, whereas at lower T the faster density fluctuations also appear in the same time window. Near T g, the PCS in the depolarized mode detects orientation fluctuations in the mixture that exhibit very broad distributions of relaxation times ( β KWW ≈ 0.2). The results are described in terms of the Kohlrausch-Williams-Watts (KWW) relaxation function and discussed in terms of the coupling scheme of relaxation.

Dynamics in Concentrated Solutions of Poly(methyl methacrylate)/Bis(2-ethylhexyl phthalate)

Photon correlation spectroscopy (PCS) and dielectric spectroscopy (DS) are employed to study the dynamics of density fluctuations at temperatures above and below the T g and the dynamics of concentration fluctuations above T g in concentrated solutions of poly(methylmethacrylate)/bis(2-ethylhexyl phthalate) (PMMA/DOP). The PCS measurements covered the temperature range between 252 and 313 K, and the DS measurements were made between 200 and 398 K and in the frequency range between 10 -2 and 10 5 Hz. Above T g the polarized PCS correlation functions contain contributions from both density and concentration fluctuations for a range of temperatures

RDF investigations on concentrated solutions of poly( p-phenylene-1,3,4-oxadiazole) in sulphuric acid

Reduced radial distribution functions (RDFs) for non-crystalline solutions of poly( p-phenylene-1,3,4-oxadiazole) (POD) in H 2SO 4 have been determined and discussed for the first time. In solutions of up to 14 wt% POD in H 2SO 4 the POD monomeric units act as simple perturbations of the correlation lattice of the pure solvent. Between 14 and 15 wt% POD content a phase transition from isotropic solution to crystal solvates and H 2SO 4 occurs. The short range interactions of POD molecules with the correlation lattice of a 96.2 wt% aqueous H 2SO 4 solvent are considerably stronger than for the same POD content in a 100% H 2SO 4 solvent.

Late stages of phase separation/gelation of isotropic solutions of rod-like polymers by video microscopy

The late stages of phase separation/gelation in concentrated solutions of poly(γ-benzyl-α, L-glutamate) in N,N-dimethylformamide containing 2% added water have been observed by video optical microscopy. Microscopic phase separation is directly evident on cooling homogeneous, isotropic solutions. Within the phase separating mixture, diffuse structural features are separated from one another by a characteristic distance. Fourier transforms of the real space images, equivalent to scattering patterns, show a radially symmetric ring, which collapses to lower wave number as gelation proceeds. The wave number associated with the maximum intensity, qm, obeys a scaling relationship consistent with the Lifshitz–Slyozov evaporation/condensation model, also consistent with the Binder–Stauffer cluster dynamics model: qm=t−1/3, where t is time. A more general scaling relationship proposed by Furukawa is obeyed very well if the dimensionality of the growth of the new phases is 3. The advantages of video microscopy for such studies and possible implications for the role of spinodal decomposition in rod-like polymer solutions are discussed.

Translational diffusion of 12-arm star polystyrenes in dilute and concentrated poly(vinyl methyl ether) solutions

The technique of dynamic light scattering from isorefractive ternary solutions has been used to study the translational diffusion behaviour of 12-arm star polystyrenes (PS) in dilute and concentrated solutions of poly(vinyl methyl ether) (PVME). PS molecular weights ranged from 5.5 × 10 4 to 1.69 × 10 6. The PVME molecular weight was 1.4 × 10 5, and the PVME concentration was varied from 0.001 to 0.30 g ml −1. The concentration dependence of diffusion is well described by the functional form D D 0 = exp(−ac u) , although there is some evidence that the star dimensions decrease with increasing PVME concentration. Comparison with the diffusion behaviour of linear PS in PVME solutions suggests that, for these molecular weights of PS and PVME, the diffusant topology is not important, and thus reptation is not a significant mechanism under these conditions. At the same time, neither the Stokes-Einstein relation nor a simple scaling function, f( R ξ ) , can describe the observed behaviour. These results are interpreted as reflecting substantial PVME mobility, relative to the PS stars.

Effect of the formation of liquid-crystalline order on parameters of helix-coil conformation transition in poly- γ-benzyl- L-glutamate

It was shown by IR spectroscopy that the formation of liquid-crystalline order in concentrated solutions of poly- γ-benzyl- L-glutamate in a mixed solvent does not further stabilize the helix structure of a polypeptide chain but increases the helix-coil cooperative inverted conformation transition.

Dielectric Normal Mode Process in Semidilute and Concentrated Solutions of Poly(2,6-dichloro-1,4-phenylene oxide)

The dielectric normal mode process was investigated on semi-dilute and concentrated solutions of poly(2,6-dichloro-1,4-phenylene oxide)(PDCPO-M) in a good solvent, chlorobenzene, at 300 K. Four linear, short chain samples with molecular weight M less than 20×103, two nearly linear samples of intermediate M, and a high M, randomly branched sample (PDCPO-380) of M=380×103 were used. The dielectric relaxation time τ for 40 wt% solutions of the linear samples was approximately proportional to M2, indicating Rouse behavior of non-entangled chains. The loss curves of the PDCPO-17 solutions were symmetrical in shape, and the half width A increased slightly with increasing concentration C due presumably to the increase in the local friction constant ζ. On the other hand, for the branched, high M PDCPO-380 sample, its loss curve not only became broader with increasing C, but split into two peaks at about C=30 wt%. This is presumably because the relaxation time of longer branches of the sample were retarded more strongly by entanglement. From the relaxation strength, the mean square end-to-end distance ‹r2› was determined as a function of C for PDCPO-17 solutions. The slope of the log‹r2› vs. logC plot was approximately −0.08 in the range of 0.2<C<1.0. This value is much smaller than −0.25 expected from the scaling theory. This discrepancy may be attributed to the weak excluded volume effect for the low molecular weight sample.

Zero-shear viscosity of dilute to moderately concentrated solutions of poly[2-methoxy-4, 6-di-(p, p′-isopropylidene diphenyloxy)-s-triazine

Abstract Zero-shear viscosities of solutions of poly [2-methoxy-4,6-di(p, p′-isopropylidene diphenyloxy)-s-triazine] in chloroform were measured at various temperatures. The viscosity data were analyzed in terms of Martin's and Fedor's relationships. The temperature dependence of viscosities indicates that the apparent activation energy for viscous flow increases and the preexponential factor, related to activation entropy, decreases with concentration of polymer solution. The parameter Cm, related to volume fraction of polymer φm, was found to be linearly dependent on temperature. The viscosity-concentration data were generalized in terms of reduced variables.

Temperature and chainlength dependence of thermodynamic properties of poly(ethylene glycol)s in ethylbenzene

AbstractVapour pressures in concentrated solutions of poly(ethylene glycol)s (M̄n = 300, 400, 600, 1000, 1500, 2000, 4000 and 6000 g/mol) in ethylbenzene have been measured in the temperature range of 303.15 K to 403.15 K and segment‐molar excess Gibbs energies \documentclass{article}\pagestyle{empty}\begin{document}$\overline{\overline G} ^E $\end{document} have been calculated. Results are discussed on the basis of free volume concepts and the UNIFAC‐model.

Pretransitional effects in the isotropic phase of a lyotropic polymer liquid crystal

AbstractConsolidation of chiral orientational ordering in concentrated solutions of poly(benzylglutamates) has been investigated by polarization microscopy, measurements of birefringence and optical rotatory dispersion. A pretransitional region was examined where the temperature and concentration of polymer are held just below critical conditions for phase separation of anisotropic, liquid crystal spherulites. Optical rotations observed in this visually isotropic region are considerably in excess of those found in dilute solution of the polymer and exhibit a strong temperature dependence. This critical enhancement of optical activity is attributable to short‐range chiral ordering of the long axes of macromolecules in the isotropic phase.