Association behavior of binary polymer mixtures under elongational flow

The influence of elongational flow on the association behavior of binary mixtures of functionalized polymers capable of forming single reversible orientationally dependent bonds, such as hydrogen bonds, is studied analytically. Applying a mean-field approach with an external potential representing the effect of the elongational flow, the orientation distribution functions for the dumbbell model and the freely jointed model of a polymer chain were obtained. Two opposite factors determine the association of “linear” diblock copolymerlike chains: the unfavorable extra stretching under flow of associated polymer chains and the favorable orientation of the chains (segments) along the flow direction. The former dominates and the fraction of associated “linear” chains decreases with increasing flow rate. For mixtures of polymers which are capable of forming associated T-chains, the association also decreases, however, more slowly, and this time due to unfavorable orientational effects. If the formation of associated linear and T-polymers as well as complex linear/T-polymers is possible, a strong preference for the formation of associated T-chains is found. At high flow rates any type of association becomes unfavorable

On the Adsorption of Two-State Polymers

Monte Carlo(MC) simulations produce evidence that annealed copolymers incorporating two interconverting monomers, P and H, adsorb as homopolymers with an effective adsorption energy per monomer, $\epsilon_{eff}$, that depends on the PH equilibrium constants in the bulk and at the surface. The cross-over exponent, $\Phi,$ is unmodified. The MC results on the overall PH ratio, the PH ratio at the surface and in the bulk as well as the number of adsorbed monomers are in quantitative agreement with this hypothesis and the theoretically derived $\epsilon_{eff}$. The evidence suggests that the form of surface potential does not affect $\Phi$ but does influence the PH equilibrium.Comment: 22 pages, 10 figure

RAFT aqueous dispersion polymerization yields poly(ethylene glycol)-based diblock copolymer nano-objects with predictable single phase morphologies

A poly(ethylene glycol) (PEG) macromolecular chain transfer agent (macro-CTA) is prepared in high yield (>95%) with 97% dithiobenzoate chain-end functionality in a three-step synthesis starting from a monohydroxy PEG113 precursor. This PEG113-dithiobenzoate is then used for the reversible addition-fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA). Polymerizations conducted under optimized conditions at 50 °C led to high conversions as judged by 1H NMR spectroscopy and relatively low diblock copolymer polydispersities (Mw/Mn < 1.25) as judged by GPC. The latter technique also indicated good blocking efficiencies, since there was minimal PEG113 macro-CTA contamination. Systematic variation of the mean degree of polymerization of the core-forming PHPMA block allowed PEG113-PHPMAx diblock copolymer spheres, worms, or vesicles to be prepared at up to 17.5% w/w solids, as judged by dynamic light scattering and transmission electron microscopy studies. Small-angle X-ray scattering (SAXS) analysis revealed that more exotic oligolamellar vesicles were observed at 20% w/w solids when targeting highly asymmetric diblock compositions. Detailed analysis of SAXS curves indicated that the mean number of membranes per oligolamellar vesicle is approximately three. A PEG 113-PHPMAx phase diagram was constructed to enable the reproducible targeting of pure phases, as opposed to mixed morphologies (e.g., spheres plus worms or worms plus vesicles). This new RAFT PISA formulation is expected to be important for the rational and efficient synthesis of a wide range of biocompatible, thermo-responsive PEGylated diblock copolymer nano-objects for various biomedical applications

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Equilibrium Chain Exchange Kinetics of Diblock Copolymer Micelles: Tuning and Logarithmic Relaxation

A systematic study of the equilibrium chain exchange kinetics of a tunable model system for starlike polymeric micelles is presented. The micelles are formed by well-defined highly asymmetrical poly( ethylene-propylene)-poly( ethylene oxide) (PEP-PEO) diblock copolymers. Mixtures of N,N-dimethylformamide (DMF) and water are used as selective solvents for PEO. With respect to PEP this solvent mixture allows the interfacial tension, gamma, to be tuned over a wide range. The equilibrium chain exchange between these micelles has been investigated using a novel time-resolved small-angle neutron scattering (TR-SANS) technique. The results show that the exchange kinetics is effectively frozen for large interfacial tensions but can be readily tuned to accessible time scales ( minutes to hours) by lowering gamma. Independent of temperature and concentration, the corresponding relaxation functions show an extremely broad and heterogeneous logarithmical decay over several decades in time. We explicitly show that such broad relaxation cannot be explained by polydispersity or a classical distribution of activation energies. Instead, the logarithmic time dependence points toward a complex relaxation picture where the chains are slowed down due to mutual topological and geometrical interactions. We propose that the behavior stems from constrained core dynamics and correlations between the expulsion probability of a chain and its conformation