Model Systems for Evidencing the Mediator Role of Riboflavin in the UVA Cross-Linking Treatment of Keratoconus.

Riboflavin under UVA radiation generates reactive oxygen species (ROS) that can induce various changes in biological systems. Under controlled conditions, these processes can be used in some treatments for ocular or dermal diseases. For instance, corneal cross-linking (CXL) treatment of keratoconus involves UVA irradiation combined with riboflavin aiming to induce the formation of new collagen fibrils in cornea. To reduce the damaging effect of ROS formed in the presence of riboflavin and UVA, the CXL treatment is performed with the addition of polysaccharides (dextran). Hyaluronic acid is a polysaccharide that can be found in the aqueous layer of the tear film. In many cases, keratoconus patients also present dry eye syndrome that can be reduced by the application of topical solutions containing hyaluronic acid. This study presents physico-chemical evidence on the effect of riboflavin on collagen fibril formation revealed by the following methods: differential scanning microcalorimetry, rheology, and STEM images. The collagen used was extracted from calf skin that contains type I collagen similar to that found in the eye. Spin trapping experiments on collagen/hyaluronic acid/riboflavin solutions evidenced the formation of ROS species by electron paramagnetic resonance measurements.

Novel Gemini Surfactant for Binding Eu(III)-Polyoxometalate into Hydrogels and Polymer Latexes.

The incorporation of rare-earth ions into polymer matrices can lead to useful materials in various fields such as biomarkers, lasers, luminescent devices, optical storage materials, and so on. Methods of incorporation are either extremely simple, such as mixing the polymer and the ion of interest in adequate solvents, or more sophisticated such as synthesizing predesigned monomers that contain the rare-earth ion or binding the ion on an already formed polymer chain. Cationic gemini surfactants represent a class of surfactants that can be used to incorporate metal-oxygen cluster compounds by means of strong electrostatic interactions. In this study, first, a novel cationic gemini surfactant having double bonds on both side chains was designed and prepared. After characterization, the surfactant was used to synthesize hydrogels with different degrees of crosslinking and also as a surfmer in emulsion polymerization of methyl methacrylate. The resulted polymer matrices were able to bind europium-polyoxometalate Na9[EuW10O36].32H2O. In case of luminescent lanthanide ions, changing the microenvironment around the metal ion also changes the intensity of some emission peaks as well as other luminescent parameters. Investigation of emission spectra of Eu3+ indicates a decrease in the symmetry of the microenvironment, when the polyanions pass from water to latex, to surfactant solution, and to hydrogel.

3D Porous Collagen Matrices-A Reservoir for In Vitro Simultaneous Release of Tannic Acid and Chlorhexidine.

The treatment of wounds occurring accidentally or as a result of chronic diseases most frequently requires the use of appropriate dressings, mainly to ensure tissue regeneration/healing, at the same time as treating or preventing potential bacterial infections or superinfections. Collagen type I-based scaffolds in tandem with adequate antimicrobials can successfully fulfill these requirements. In this work, starting from the corresponding hydrogels, we prepared a series of freeze-dried atelocollagen type I-based matrices loaded with tannic acid (TA) and chlorhexidine digluconate (CHDG) as active agents with a broad spectrum of antimicrobial activity and also as crosslinkers for the collagen network. The primary aim of this study was to design an original and reliable algorithm to in vitro monitor and kinetically analyze the simultaneous release of TA and CHDG from the porous matrices into an aqueous solution of phosphate-buffered saline (PBS, pH 7.4, 37 °C) containing micellar carriers of a cationic surfactant (hexadecyltrimethylammonium bromide, HTAB) as a release environment that roughly mimics human extracellular fluids in living tissues. Around this central idea, a comprehensive investigation of the lyophilized matrices (morpho-structural characterization through FT-IR spectroscopy, scanning electron microscopy, swelling behavior, resistance against the collagenolytic action of collagenase type I) was carried out. The kinetic treatment of the release data displayed a preponderance of non-Fickian-Case II diffusion behavior, which led to a general anomalous transport mechanism for both TA and CHDG, irrespective of their concentrations. This is equivalent to saying that the release regime is not governed only by the gradient concentration of the releasing components inside and outside the matrix (like in ideal Fickian diffusion), but also, to a large extent, by the relaxation phenomena of the collagen network (determined, in turn, by its crosslinking degree induced by TA and CHDG) and the dynamic capacity of the HTAB micelles to solubilize the two antimicrobials. By controlling the degree of physical crosslinking of collagen with a proper content of TA and CHDG loaded in the matrix, a tunable, sustainable release profile can be obtained.

Interaction between Albumin and Pluronic F127 Block Copolymer Revealed by Global and Local Physicochemical Profiling.

The interaction of human serum albumin (HSA) with amphiphilic block copolymer Pluronic F127 has been investigated by several physical methods. Interest in studying this system stems from a broad range of bioactivities involving both macromolecules. Serum albumins constitute a significant class of proteins in the circulatory system, acting as carriers for a wide spectrum of compounds or assemblies. Pluronic block copolymers have revealed their capacity to ferry a variety of biologically active compounds. Circular dichroism, rheological measurements, and differential scanning microcalorimetry (µDSC) were employed to get insight into the interaction betweeen the two macromolecules. The results reveal that Pluronic F127 induces conformational changes to albumin if it is organized in a micellar form, while albumin influences the self-assembly of Pluronic F127 into micelles or gels. F127 micelles, however, induce smaller conformational changes compared to ionic surfactants. The µDSC thermograms obtained for HSA and/or F127 show that HSA shifts the critical micellar temperature (cmt) to lower values, while concurrently the HSA denaturation behavior is influenced by F127, depending on its concentration. Rheological measurements on solutions of F127 17% have shown that a sol-to-gel transition occurs at higher temperatures in the presence of HSA and the resulting gel is weaker. The global profile on HSA/F127 systems was complemented by local information provided by EPR measurements. A series of X-band EPR experiments was performed with spin probes 4-(N,N'-dimethyl-N-hexadecyl)ammonium-2,2',6,6'-tetramethylpiperidine-1-oxyl iodide (CAT16) and 5-doxyl stearic acid (5-DSA). These spin probes bind to albumin sites and are sensitive to phase transformations in Pluronic block copolymer solutions. For a given F127 concentration, the spin probe binds only to HSA below cmt and migrates to the F127 micelles above cmt. The collective data suggest soft interactions between the macromolecules, with the emerging results projecting potential applications linked to reaching optimal conditions for certain drug formulations.

Luminescent liquid crystalline materials based on palladium(II) imine derivatives containing the 2-phenylpyridine core.

In this work we report our studies concerning the synthesis and characterisation of a series of imine derivatives that incorporate the 2-phenylpyridine (2-ppy) core. These derivatives were used in the cyclometalating reactions of platinum(II) or palladium(II) in order to prepare several complexes with liquid crystalline properties. Depending on the starting materials used as well as the solvents employed, different metal complexes were obtained, some of them showing both liquid crystalline behaviour and luminescence properties at room temperature. It was found that, even if there are two competing coordination sites, the cyclometalation process takes place always at the 2-ppy core with (for Pt) or without (for Pd) the imine bond cleavage. We successfully showed that it is possible to prepare emissive room temperature liquid crystalline materials based on double cyclopalladated heteroleptic complexes by varying the volume fraction of the long flexible alkyl tails on the ancillary benzoylthiourea (BTU) ligands.