Non-covalent modification of single wall carbon nanotubes (SWCNTs) by thienothiophene derivatives.

Non-covalent functionalization of single wall carbon nanotubes (SWCNTs) has been conducted using several binding agents with surface π-interaction forces in recent studies. Herein, we present the first example of non-covalent functionalization of sidewalls of SWCNTs using thienothiophene (TT) derivatives without requiring any binding agents. Synthesized TT derivatives, TT-CN-TPA, TT-CN-TPA2 and TT-COOH-TPA, were attached directly to SWCNTs through non-covalent interactions to obtain new TT-based SWCNT hybrids, HYBRID 1-3. Taking advantage of the presence of sulfur atoms in the structure of TT, HYBRID 1, as a representative, was treated with Au nanoparticles for the adsorption of Au by sulfur atoms, which generated clear TEM images of the particles. The images indicated the attachment of TTs to the surface of SWCNTs. Thus, the presence of sulfur atoms in TT units made the binding of TTs to SWCNTs observable via TEM analysis through adsorption of Au nanoparticles by the sulfur atoms. Surface interactions between TTs and SWCNTs of the new hybrids were also clarified by classical molecular dynamic simulations, a quantum mechanical study, and SEM, TEM, AFM and contact angle (CA) analyses. The minimum distance between a TT and a SWCNT reached up to 3.5 Å, identified with strong peaks on a radial distribution function (RDF), while maximum interaction energies were raised to -316.89 kcal mol-1, which were determined using density functional theory (DFT).

Poly(L-lactic acid)/poly(ethylene oxide) based composite electrospun fibers loaded with magnesium-aluminum layered double hydroxide nanoparticles.

Two types of MgAl layered double hydroxide nanoparticles, MgAl LDH, at Mg:Al ratio of 2:1 and 3:1were prepared and used as inorganic fillers to improve the mechanical properties of poly(lactic acid)/poly(ethylene oxide) (PLA/PEO) electrospun composite fibers. Their detailed structural characterization was performed using X-ray diffraction (XRD) and transmission electron spectroscopy (TEM) techniques. Spectroscopic, thermal, mechanical, and morphological properties of the electrospun composite fibers, and cell proliferation on their surface, were examined. XRD and TEM analyses showed that the LDH nanoparticles were 50 nm in size and the Mg:Al ratio did not affect the average spacing between crystal layers. Fourier transform infrared (FTIR) and thermal analyses (TA) revealed the compatibility of the filler and the polymer matrix. The nanoparticles considerably improved the mechanical properties of the electrospun mats. The tensile strength and elongation at break values of the composite samples increased from 0.22 MPA to 0.40 MPa and 12.2 % to 45.66 %, respectively, resulting from the interaction between LDH and the polymer matrix. Scanning electron microscopy (SEM) and MTT analyses demonstrated that the electrospun composite fibers supported the SaOS-2 cells attachment and proliferation on the fiber surfaces, along with their suitable cytocompatibility.

Concise synthesis of 3-alkylthieno[3,2-b]thiophenes; building blocks for organic electronic and optoelectronic materials.

Four step synthesis of 3-alkylthieno[3,2-b]thiophenes in the literature was reduced to two steps in good yields, through the preparation of the mono ketone, i.e. 1-(thiophene-3-ylthio)alkan-2-one, from 3-bromothiophene and ring formation reaction. This convenient method provides an easy access with good yields to the preparation of 3-alkylthieno[3,2-b]thiophenes, which are important materials for organic electronic and optoelectronic applications. SEM, AFM and contact angle (CA) analyses of their electropolymers on indium tin oxide (ITO) indicated that as the alkyl chains became longer, the polymers provide a more hydrophobic layer with CA up to 107°.

Beta-Glucan based temperature responsive hydrogels for 5-ASA delivery.

A series of temperature responsive hydrogels consisting of (1,3)-(1,6) ß-Glucan and poly (N-isopropyl acrylamide) (PNIPAM) was synthesized by redox polymerization at room temperature. Tetramethylethylenediamine (TEMED) and potassium persulfate (KPS) were used as a redox pair. ß-glucan was methacrylated (MA-ß-Glucan) and used as a biodegradable and bio-compatible cross-linker to prepare ß-glucan-PNIPAM based temperature responsive hydrogels. Swelling behavior of the hydrogels at different temperatures was investigated. The 5-ASA release from the hydrogels was monitored using UV-VIS spectrophotometer at 37 °C. It is notable that, the swelling and release behaviors of the hydrogels significantly change depending on the hydrogel compositions and temperature. Their thermal stability was determined using thermogravimetric analysis (TGA), assuming the extent of intermolecular interaction between PNIPAM and ß-glucan is proportional to thermal stability, which increased with the amount of PNIPAM. Volume phase transition temperature (VPTT) of the hydrogels was precisely determined by derivative differential scanning calorimeter (DDSC). They possessed variable VPTT with the compositions. The presence of ß-glucan in the PNIPAM network brought VPTT closer to the body temperature (from 32.8 °C to 35.5 °C), indicating that the VPTT could be tuned by the hydrogel compositions. Their in-vivo biocompatibility was tested against WS1 human fibroblast cells in phosphate buffer saline (PBS, pH 7.4). It was demonstrated that, using MA-ß-glucan as a cross-linker resulted in more bio-compatible thermo-responsive hydrogels indicating the enhancement of hydrophilic ß-Glucan on the swollen hydrogel surface.

Novel levan and pNIPA temperature sensitive hydrogels for 5-ASA controlled release.

Levan based cross-linker was successfully synthesized and used to prepare a series of more biocompatible and temperature responsive levan/N-isopropyl acrylamide (levan/pNIPA) hydrogels by redox polymerization at room temperature. Volume phase transition temperature (VPTT) of the hydrogels were precisely determined by derivative differential scanning calorimetry (DDSC). Incorporation of levan into the pNIPA hydrogel increased the VPTT from 32.8°C to 35.09°C, approaching to body temperature. Swelling behavior and 5-aminosalicylic acid (5-ASA) release of the hydrogels were found to vary significantly with temperature and composition. Moreover, a remarkable increase in thermal stability of levan within hydrogel with increase of pNIPA content was recorded. The biocompatibility of the hydrogels were tested against mouse fibroblast L929 cell line in phosphate buffer saline (PBS, pH 7.4). The hydrogels showed increasing biocompatibility with increasing levan ratio, indicating levan enhanced the hydrogel surface during swelling.

Sugar Based Biopolymers in Nanomedicine; New Emerging Era for Cancer Imaging and Therapy.

Since last decade, sugar based biopolymers are recognized in nanomedicine as promising materials for cancer imaging and therapy. Their durable, biocompatible and adhesive properties enable the fine tuning of their molecular weights (MW) and their miscellaneous nature makes the molecules acquire various conformations. These in turn provide effective endocytosis by cancer cell membranes that have already been programmed for internalization of different kinds of sugars. Therefore, biocompatible sugar based nanoparticles (SBNPs) are suitable for both cell-selective delivery of drugs and imaging through the human body. Recently, well known sugar-based markers have displayed superior performance to overcome tumor metastasis. Thereby, targeting strategies for cancer cells have been broadened to sugar-based markers as noticed in various clinic phases. In these studies, biopolymers such as chitosan, hyaluronic acid, mannan, dextran, levan, pectin, cyclodextrin, chondroitin sulphate, alginates, amylose and heparin are chemically functionalized and structurally designed as new biocompatible nanoparticles (NPs). The future cancer treatment strategies will mainly comprise of these multifunctional sugar based nanoparticles which combine the therapeutic agents with imaging technologies with the aim of rapid monitoring response to therapies. While each individual imaging and treatment step requires a long time period in effective treatment of diseases, these multifunctional sugar based nanoparticles will have the advantage of rapid detection, right drug efficiency evaluation and immediate interfere opportunity to some important diseases, especially rapidly progressing cancers. In this article, we evaluated synthesis, characterization and applications of main sugar based biopolymers and discussed their great promise in nano-formulations for cancer imaging and therapy. However much should be done and optimized prior to clinical applications of these nano-formulations for an efficient drug treatment without overall toxicity for getting most effective clinical results.

Sulfated levan from Halomonas smyrnensis as a bioactive, heparin-mimetic glycan for cardiac tissue engineering applications.

Chemical derivatives of levan from Halomonas smyrnensis AAD6(T) with low, medium and high levels of sulfation were synthesized and characterized by FTIR and 2D-NMR. Sulfated levan samples were found to exhibit anticoagulation activity via the intrinsic pathway like heparin in a dose-dependent manner. Exceptionally high heparin equivalent activity of levan sulfate was shown to proceed via thrombin inhibition where decreased Factor Xa activity with increasing concentration was observed in antithrombin tests and above a certain concentration, levan sulfate showed a better inhibitor activity than heparin. In vitro experimental results were then verified in silico by docking studies using equilibrium structures obtained by molecular dynamic simulations and results suggested a sulfation dependent binding mechanism. With its high biocompatibility and heparin mimetic activity, levan sulfate can be considered as a suitable functional biomaterial to design biologically active, functionalized, thin films and engineered smart scaffolds for cardiac tissue engineering applications.

Sequence specific recognition of ssDNA by fluorophore 3-hydroxyflavone.

A fully water soluble 3-hydroxyflavone (3HF) derivative, N-(3-hydroxy-4'-flavonyl)-N,N,N-trimethylammonium sulfate (3HFNMe3) was synthesized. Investigation of its emissions at varying wavelengths revealed that it had three emission bands of normal (N(⁎)), anionic (A(⁎)) and tautomeric (T(⁎)), in ultrapure water. Recognition of single-stranded ten ssDNA chains, having different nucleotide sequences was studied, using the ratiometric change of the intensities of the two bands (A(⁎)/T(⁎)), depending upon the varying environment of the 3HFNMe3 with different ssDNA chains. Addition of the ssDNA chains to the 3HFNMe3 solution caused gradual quenching of the A(⁎) band and had almost no effect on the T(⁎) band. As the ratios of the two bands (A(⁎)/T(⁎)) vs increasing amount of the ssDNAs generated characteristic curves for each ssDNA chain, it became possible to identify the chains with their characteristic curves.

Combinatorial MAPLE gradient thin film assemblies signalling to human osteoblasts.

There is increased interest in smart bioactive materials to control tissue regeneration for the engineering of cell instructive scaffolds. We introduced combinatorial matrix-assisted pulsed laser evaporation (C-MAPLE) as a new method for the fabrication of organic thin films with a compositional gradient. Synchronized C-MAPLE of levan and oxidized levan was employed to assemble a two-compound biopolymer film structure. The gradient of the film composition was validated by fluorescence microscopy. In this study, we investigated the cell response induced by the compositional gradient using imaging of early osteoblast attachment and analysis of signalling phosphoprotein expression. Cells attached along the gradient in direct proportion to oxidized levan concentration. During this process distinct areas of the binary gradient have been shown to modulate the osteoblasts' extracellular signal-regulated kinase signalling with different propensity. The proposed fabrication method results in the preparation of a new bioactive material, which could control the cell signalling response. This approach can be extended to screen new bioactive interfaces for tissue regeneration.

A new lipid-based nano formulation of vinorelbine.

Vinorelbine (VLB) is a semi-synthetic Vinca alkaloid which is currently used in treatment of different cancer types mainly advanced breast cancer (ABC) and advanced/metastatic non-small cell lung cancer (NSCLC). However, its marketed formulation has been reported to have serious side effects, such as granulocytopenia, which is the major dose-limiting toxicity. Other unwanted effects include venous discoloration and phlebitis proximal to the site of injection, as well as localized rashes and urticaria, blistering, and skin sloughing. Our long-term aim in synthesizing a novel nanomicellar vinorelbine formulation is to reduce or even eliminate these side effects and increase drug activity by formulating the drug in a lipid-based system as a nanomedicine targeted to the site of action. To this end, the purpose of this study was to prepare, characterize, and determine the in vitro efficacy of vinorelbine-loaded sterically stabilized, biocompatible, and biodegradable phospholipid nanomicelles (SSM; size, ∼15 nm). Our results indicated that vinorelbine incorporate at high quantities and within the interface between the core and palisade sections of the micelles. Incorporation ratio of drug within sterically stabilized micelles increased as the total amount of drug in the system increased, and no drug particles were formed at the highest drug concentrations tested. The nanomicellar formulation of vinorelbine was ∼6.7-fold more potent than vinorelbine dissolved in DMSO on MCF-7 cell line. Collectively, these data indicate that vinorelbine-loaded SSM can be developed as a new, safe, stable, and effective nanomedicine for the treatment of breast and lung cancers.

Comprehensive characterization of chitosan/PEO/levan ternary blend films.

Ternary blend films of chitosan, PEO (300,000) and levan were prepared by solution casting method and their phase behavior, miscibility, thermal and mechanical properties as well as their surface energy and morphology were characterized by different techniques. FT-IR analyses of blend films indicated intermolecular hydrogen bonding between blend components. Thermal and XRD analysis showed that chitosan and levan suppressed the crystallinity of PEO up to nearly 25% of PEO content in the blend, which resulted in more amorphous film structures at higher PEO/(chitosan+levan) ratios. At more than 30% of PEO concentration, contact angle (CA) measurements showed a surface enrichment of PEO whereas at lower PEO concentrations, chitosan and levan were enriched on the surfaces leading to more amorphous and homogenous surfaces. This result was further confirmed by atomic force microscopy (AFM) images. Cell proliferation and viability assay established the high biocompatibility of the blend films.

Controlled release of 5-aminosalicylicacid from chitosan based pH and temperature sensitive hydrogels.

A series of temperature and pH responsive hydrogels based on chitosan and poly(N-isopropyl acrylamide) (PNIPA) was prepared by redox polymerization. Effect of the composition on swelling behavior of the hydrogels and the release of 5-aminosaylcilic acid (5-ASA) at different temperatures and pHs have been investigated. Ammonium persulphate and TEMED were used as a redox pair at room temperature. As a cross linker, methacrylated chitosan was synthesized through the reaction of chitosan with glycidyl methacrylate (GMA). Introduction of the cross-linker provided the hydrogels with pH and temperature sensitivities. The phase transition temperatures of the hydrogels were determined by derivative differential scanning calorimeter (DDSC). Their phase transition temperatures were increased by chitosan content. Swelling behaviors and the release of 5-ASA varied significantly with pH, temperature and the gel composition. The release of 5-ASA from the hydrogels was followed by UV-Vis and fluorescence spectroscopy.

Levan nanostructured thin films by MAPLE assembling.

Synthesis of nanostructured thin films of pure and oxidized levan exopolysaccharide by matrix-assisted pulsed laser evaporation is reported. Solutions of pure exopolysaccharides in dimethyl sulfoxide were frozen in liquid nitrogen to obtain solid cryogenic pellets that have been used as targets in pulsed laser evaporation experiments with a KrF* excimer source. The expulsed material was collected and assembled onto glass slides and Si wafers. The contact angle studies evidenced a higher hydrophilic behavior in the case of oxidized levan structures because of the presence of acidic aldehyde-hydrogen bonds of the coating formed after oxidation. The obtained films preserved the base material composition as confirmed by Fourier transform infrared spectroscopy. They were compact with high specific surface areas, as demonstrated by scanning electron and atomic force microscopy investigations. In vitro colorimetric assays revealed a high potential for cell proliferation for all coatings with certain predominance for oxidized levan.