With the discovery of important biological roles of carbon monoxide (CO), the use of this gas as a therapeutic agent has attracted attention. However, the medical application of this gas has been hampered by the complexity of the administration method. To overcome this problem, several transition-metal carbonyl complexes, such as Ru(CO)(3)Cl(glycinate), [Ru(CO)(3)Cl(2)](2), and Fe(η(4)-2-pyrone)(CO)(3), have been used as CO-releasing molecules both in vitro and in vivo. We sought to develop micellar forms of metal carbonyl complexes that would display slowed diffusion in tissues and thus better ability to target distal tissue drainage sites. Specifically, we aimed to develop a new CO-delivery system using a polymeric micelle having a Ru(CO)(3)Cl(amino acidate) structure as a CO-releasing segment. The CO-releasing micelles were prepared from triblock copolymers composed of a hydrophilic poly(ethylene glycol) block, a poly(ornithine acrylamide) block bearing Ru(CO)(3)Cl(ornithinate) moieties, and a hydrophobic poly(n-butylacrylamide) block. The polymers formed spherical micelles in the range of 30-40 nm in hydrodynamic diameter. Further characterization revealed the high CO-loading capacity of the micelles. CO-release studies showed that the micelles were stable in physiological buffer and serum and released CO in response to thiol-containing compounds such as cysteine. The CO release of the micelles was slower than that of Ru(CO)(3)Cl(glycinate). In addition, the CO-releasing micelles efficiently attenuated the lipopolysaccharide-induced NF-κB activation of human monocytes, while Ru(CO)(3)Cl(glycinate) did not show any beneficial effects. Moreover, cell viability assays revealed that the micelles significantly reduced the cytotoxicity of the Ru(CO)(3)Cl(amino acidate) moiety. This novel CO-delivery system based on CO-releasing micelles may be useful for therapeutic applications of CO.

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The natural turnover of free hyaluronic acid (HA) is predominantly based on its CD44-mediated internalisation in leukocytes. In a phagocytic cell model (RAW 264.7 murine macrophages) we here provide conclusive evidence that this receptor-mediated mechanism endocytosis is responsible also of the uptake of materials where HA is used as a coating agent, in this case chitosan/triphosphate nanoparticles on whose surface HA is electrostatically adsorbed. Alginate-coated nanoparticles were used as a control and they appeared to undergo a qualitatively similar endocytic process, which was mediated by a different scavenging receptor yet to be identified. In this general picture, an important, modulating role appears to be played by how receptors can cluster around individual nanoparticles. The CD44 slow representation (24-48 h) enforces a limit in the amount of available HA internalisation receptors; therefore a higher affinity, and hence a higher degree of clustering, would yield a lower number of internalised nanoparticles. HA presentation can be varied by acting on nanoparticle structure/morphology, and our data suggest that a better presentation may be linked to both higher affinity and lower capacity/uptake rate. Paradoxically, this result would suggest that particles with a lower affinity for CD44 may allow a more efficient HA-mediated delivery of payloads.

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Pegylation using heterotelechelic poly(ethylene glycol) (PEG) offers many possibilities to create high-performance molecules and materials. A versatile route is proposed to synthesize heterobifunctional PEG containing diverse combinations of azide, amine, thioacetate, thiol, pyridyl disulfide, as well as activated hydroxyl end groups. Asymmetric activation of one hydroxyl end group enables the heterobifunctionalization while applying selective monotosylation of linear, symmetrical PEG as a key step. The azide function is introduced by reacting monotosyl PEG with sodium azide. A thiol end group is obtained by reaction with sodium hydrosulfide. The activation of the hydroxyl end group and subsequent reaction with potassium carbonate/thioacetic acid yields a thioacetate end group. The hydrolysis of the thioester end group by ammonia in presence of 2,2′-dipyridyl disulfide provides PEG pyridyl disulfide. Amine terminated PEG is prepared either by reduction of the azide or by nucleophilic substitution of mesylate terminated PEG using ammonia. In all cases, >95% functionalization of the PEG end groups is achieved. The PEG derivatives particularly support the development of materials for biomedical applications. For example, grafting up to 13% of the Na-alg monomer units with α-amine-ω-thiol PEG maintains the gelling capacity in presence of calcium ions but simultaneous, spontaneous disulfide bond formation reinforces the initial physical hydrogel. OPEN ACCESSPolymers 2012, 4 562

Three novel ionic monomers having highly delocalized anions and electrochemically stable mobile cations, namely, 1-butyl-1-methylpyrrolidiniumpropylsulfonyl)]methanide and 1-butyl-1-methylpyrrolidinium 1-cyano-1- [(3-(methacryloyloxy) propylsulfonyl)]imide were synthesized and characterized. The structure of these monomers was designed to be a mimic of the most highly conductive bis(trifluoromethylsulfonyl)imide, tricyanomethanide and dicyanamide anions. By radical polymerization procedure a series of new anionic ''polymeric ionic liquids'' (PILs) were prepared. The solubility of these linear PILs, thermal stability, glass transition temperatures, molar masses and ionic conductivities were estimated. An advantage of the novel PILs was demonstrated by the comparison of their ionic conductivity at 25 C (2.0 Â 10 À8 O 1.6 Â 10 À7 S cm À1 ) with the unmodified poly(1-ethyl-1-methylpyrrolidinium 3-(methacryloyloxy)propane-1-sulfonate) analog. The increase in ionic conductivity is as high as three orders of magnitude and was found to depend on the size of the attached anion. The new ionic monomers were subsequently copolymerized with poly(ethylene glycol) dimethacrylate and poly (ethylene glycol) methyl ether methacrylate. The investigation of the copolymers properties revealed further improvement of the conductivity in approximately two orders of magnitude and the achievement of s ¼ 4.8 O 6.8 Â 10 À6 S cm À1 ) at 40 C.

A general description of the electrolytic conductivity behavior of highly charged strong polyelectrolytes in dilute and semidilute aqueous solutions is presented. For the first time this model considers the influences of the molar mass, charge density (for charge distances less than the Bjerrum length), polyelectrolyte concentration, and the ionic strength adjusted by both the polyelectrolyte concentration (c p in monomol L-1) and added simple salt concentration (c s in mol L-1). Above the overlap concentration (c*) the molar mass influence is weak. Below this overlap concentration the equivalent conductivity (Λ) increases strongly with decreasing c p, as long as c p > c s. Correlations could be established for the maximum of Λ, Λmax ∼ c s -1/5 and Λmax ∼ M -2/5. The conductivity behavior can be qualitatively explained in terms of Manning's theory with an additional change of the interaction parameter f c. On the basis of this fact an empirical dependence of f c on the ratio of the Debye length to the contour length (l D/L) has been found. Three concentration regimes differing in the polyion−counterion interaction could be identified. These are characterized by l D/L located below (4π)-1/2, between (4π)-1/2 and unity, and above unity, respectively. The model description includes polyelectrolyte solutions without added salt as well as solutions with any ratio of polyelectrolyte to salt concentration. This is the first model which is based on sufficient experimental data in the highly diluted concentration regime. Therefore, it should stimulate further theoretical studies.

The radical polymerization of bis‐1,3(N,N,N‐trimethylammonium)‐2‐propylmethacrylate dichloride revealed non‐ideality with 0.59 and 4.4 for the reaction orders of the initiator and monomer concentration, respectively. Further, autoacceleration was observed from less than 10% conversion onwards. Degradative chain transfer to the monomer was concluded to explain the initiator exponent. Monomer association and electrostatic effects are hypothesized to govern the monomer exponent and autoacceleration. The exponential concentration dependent increase of the viscosity of the monomer solution and the relatively low overall activation energy Ea = 31.5 kJ · mol−1 support the hypothesis. Counterion activity measurements confirmed strong counterion condensation as expected for a charge distance of 0.12 nm.magnified image