Hyaluronic Acid Graft Copolymers with Cleavable Arms as Potential Intravitreal Drug Delivery Vehicles.

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.

Optimized triazine-mediated amidation for efficient and controlled functionalization of hyaluronic acid.

Triazine-based coupling agents have the potential to replace carbodiimides in the functionalization of hyaluronic acid (HA) giving derivatives with high degrees of substitution (DS) under mild conditions with excellent efficiency. Kinetics of the triazine-mediated amidation of HA in aqueous solution were investigated to understand the reaction mechanism and the role of the amine reagent. The DS decreased with increasing basicity of the amine. The water soluble coupling agent was stable under the reaction conditions (t1/2=10 days) in the absence of amines. The activation of HA proceeded quantitatively. The stoichiometry of amine was the limiting factor in the substitution. Functional HA derivatives with DS up to 55% were obtained by the triazine-mediated amidation. They were used successfully to prepare well-defined HA conjugates via the maleimide-thiol and the azide-alkyne "click" reactions.

ε-Decalactone: a thermoresilient and toughening comonomer to poly(L-lactide).

The renewable monomer ε-decalactone is an excellent partner to L-lactide, where their copolymers overcome inherent drawbacks of polylactide, such as low thermal stability and brittleness. ε-Decalactone is a seven-membered lactone that was successfully polymerized with Sn(Oct)(2) and 1,5,7-triazabicyclo[4.4.0]dec-5-ene into both an amorphous homopolymer and copolymers with high molecular weight, low dispersity, and predicted macromolecular architecture. The thermoresilient nature of ε-decalactone is reflected in a high polymerization ceiling temperature and increased thermal stability for the prepared copolymers. The high ceiling temperature enables easy modulation of the polymerization rate via temperature while maintaining architectural control. The apparent rate constant was increased 15-fold when the temperature was increased from 110 to 150 °C. Copolymers of L-lactide and ε-decalactone, either with the latter as a central block in triblock polymers or with randomly positioned monomers, exhibited exceptionally tough material characteristics. The triblock copolymer had an elongation-at-break 250 times greater than that of pure poly(L-lactide). The toughness of the copolymers is attributed to the flexible nature of the polymer derived from the monomer ε-decalactone and to the segment immiscibility. These properties result in phase separation to soft and hard domains, which provides the basis for the elastomeric behavior.

Cavitation engineered 3D sponge networks and their application in active surface construction.

The design of the 3D architecture surfaces with both space- and time-dependent functionality (cell attraction, pH-trigged self-cleaning, antiseptic/disinfection) is in the focus. The innovative story includes: sonochemical surface activation, formation of feedback surface component (pH-responsible micelles), proof of responsive activity (time resolved cell adhesion and bacteria deactivation) and space adhesion selectivity (surface patterning).

Silver coated aluminium microrods as highly colloidal stable SERS platforms.

We report on the fabrication of a novel material with the ability to remain in solution even under the very demanding conditions required for structural and dynamic characterization of biomacromolecule assays. This stability is provided by the increase in surface area of a low density material (aluminium) natively coated with a very hydrophilic surface composed of aluminium oxide (Al(2)O(3)) and metallic silver nanoparticles. Additionally, due to the dense collection of active hot spots on their surface, this material offers higher levels of SERS intensity as compared with the same free and aggregated silver nanoparticles.