Effect of the alkyl chain length of the ionic liquid anion on polymer electrolytes properties

New polymer electrolytes (PEs) based on chitosan and three ionic liquid (IL) families ([C2mim][CnSO3], [C2mim][CnSO4] and [C2mim][diCnPO4]) were synthesized by the solvent casting method. The effect of the length of the alkyl chain of the IL anion on the thermal, morphological and electrochemical properties of the PEs was studied. The solid polymer electrolytes (SPE) membranes were analyzed by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), polarized optical microscopy (POM), atomic force microscopy (AFM), complex impedance spectroscopy (ionic conductivity) and cyclic voltammetry (CV). The obtained results evidenced an influence of the alkyl chain length of the IL anion on the temperature of degradation, birefringence, surface roughness and ionic conductivity of the membranes. The DSC, XRD and CV results showed independency from the length of the IL-anion-alkyl chain. The PEs displayed an predominantly amorphous morphology, a minimum temperature of degradation of 135 °C, a room temperature (T = 25 °C) ionic conductivity of 7.78 × 10−4 S cm−1 and a wide electrochemical window of ∼ 4.0 V.

Pró-fármacos fotoativáveis do péptido AAPV: síntese e avaliação da libertação controlada por luz

Dissertação de mestrado em Bioquímica Aplicada (área de especialização em Biomedicina)

Poly lactic acid based biodegradable stents and functionalization techniques: brief review

Commercial stents, especially metallic ones, present several disadvantages, and this gives rise to the necessity of producing or coating stents with different materials, like natural polymers, in order to improve their biocompatibility and minimize the disadvantages of metallic ones. This review paper discusses some applications of natural-based polymers in stents, namely polylactic acid (PLA) for stent development and chitosan for biocompatible coatings of stents . Furthermore, some effective stent functionalization techniques will be discussed, namely Layer by Layer (LBL) technique.

Vanishing spin stiffness in the spin-1/2 Heisenberg chain for any nonzero temperature

Whether at the zero spin density m = 0 and finite temperatures T > 0 the spin stiffness of the spin-1/2 XXX chain is finite or vanishes remains an unsolved and controversial issue, as different approaches yield contradictory results. Here we explicitly compute the stiffness at m = 0 and find strong evidence that it vanishes. In particular, we derive an upper bound on the stiffness within a canonical ensemble at any fixed value of spin density m that is proportional to m2L in the thermodynamic limit of chain length L → ∞, for any finite, nonzero temperature, which implies the absence of ballistic transport for T > 0 for m = 0. Although our method relies in part on the thermodynamic Bethe ansatz (TBA), it does not evaluate the stiffness through the second derivative of the TBA energy eigenvalues relative to a uniform vector potential. Moreover, we provide strong evidence that in the thermodynamic limit the upper bounds on the spin current and stiffness used in our derivation remain valid under string deviations. Our results also provide strong evidence that in the thermodynamic limit the TBA method used by X. Zotos [Phys. Rev. Lett. 82, 1764 (1999)] leads to the exact stiffness values at finite temperature T > 0 for models whose stiffness is finite at T = 0, similar to the spin stiffness of the spin-1/2 Heisenberg chain but unlike the charge stiffness of the half-filled 1D Hubbard model.

The contribution of phenolic acids to the anti-inflammatory activity of mushrooms: Screening in phenolic extracts, individual parent molecules and synthesized glucuronated and methylated derivatives

In the present study, the ethanolic extracts of fourteen edible mushrooms were investigated for their anti-inflammatory potential in LPS (lipopolysaccharide) activated RAW 264.7 macrophages. Furthermore the extracts were chemically characterized in terms of phenolic acids and related compounds. The identified molecules (p-hydroxybenzoic, p-coumaric and cinnamic acids) and their glucuronated and methylated derivatives obtained by chemical synthesis were also evaluated for the same bioactivity, in order to establish structure-activity relationships and to comprehend the effects of in vivo metabolism reactions in the activity of the compounds. The extracts of Pleurotus ostreatus, Macrolepiota procera, Boletus impolitus and Agaricus bisporus revealed the strongest anti-inflammatory potential (EC50 values 96 ± 1 to 190 ± 6 µg/mL, and also the highest concentration of cinnamic acid (656 to 156 µg/g), which was also the individual compound with the highest anti-inflammatory activity. The derivatives of p-coumaric acid revealed the strongest properties, specially the derivative methylated in the carboxylic group (CoA-M1) that exhibited similar activity to the one showed by dexamethaxone used as anti-inflammatory standard; by contrast, the derivatives of p-hydroxybenzoic revealed the lowest inhibition of NO production. All in all, whereas the conjugation reactions change the chemical structure of phenolic acids and may increase or decrease their activity, the glucuronated and methylated derivatives of the studied compounds are still displaying anti-inflammatory activity.

Polysaccharide-based freestanding multilayered membranes exhibiting reversible switchable properties

The design of self-standing multilayered structures based on biopolymers has been attracting increasing interest due to their potential in the biomedical field. However, their use has been limited due to their gel-like properties. Herein, we report the combination of covalent and ionic cross-linking, using natural and non-cytotoxic cross-linkers, such as genipin and calcium chloride (CaCl2). Combining both cross-linking types the mechanical properties of the multilayers increased and the water uptake ability decreased. The ionic cross-linking of multilayered chitosan (CHI)â alginate (ALG) films led to freestanding membranes with multiple interesting properties, such as: improved mechanical strength, calcium-induced adhesion and shape memory ability. The use of CaCl2 also offered the possibility of reversibly switching all of these properties by simple immersion in a chelate solution. We attribute the switch-ability of the mechanical properties, shape memory ability and the propensity for induced-adhesion to the ionic cross-linking of the multilayers. These findings suggested the potential of the developed polysaccharide freestanding membranes in a plethora of research fields, including in biomedical and biotechnological fields.

Light responsive multilayer surfaces with controlled spatial extinction capability

Multilayer systems obtained using the Layer-by-Layer (LbL) technology have been proposed for a variety of biomedical applications in tissue engineering and regenerative medicine. LbL assembly is a simple and highly versatile method to modify surfaces and fabricate robust and highly-ordered nanostructured coatings over almost any type of substrates and with a wide range of substances. The incorporation of polyoxometalate (POM) inorganic salts as constituents of the layers presents a possibility of promoting light-stimuli responses in LbL substrates. We propose the design of a biocompatible photo-responsive multilayer system based on a Preyssler-type POM ([NaP5W30O110]14â ) and a natural origin polymer, chitosan, using the LbL methodology. The photo-reduction properties of the POM allow the spatially controlled disruption of the assembled layers due to the weakening of the electrostatic interactions between the layers. This system has found applicability in detaching devices, such as the cell sheet technology, which may solve the drawbacks actually found in other cell treatment proposals.

Layer-by-layer technique to developing functional nanolaminate films with antifungal activity

The layer-by-layer (LbL) deposition method was used to build up alternating layers (five) of different polyelectrolyte solutions (alginate, zein-carvacrol nanocapsules, chitosan and chitosan-carvacrol emulsions) on an aminolysed/charged polyethylene terephthalate (A/C PET) film. These nanolaminated films were characterised by contact angle measurements and through the determination of water vapour (WVTR) and oxygen (O2TR) transmission rates. The effect of active nanolaminated films against the Alternaria sp. and Rhizopus stolonifer was also evaluated. This procedure allowed developing optically transparent nanolaminated films with tuneable water vapour and gas properties and antifungal activity. The water and oxygen transmission rate values for the multilayer films were lower than those previously reported for the neat alginate or chitosan films. The presence of carvacrol and zein nanocapsules significantly decreased the water transmission rate (up to 40 %) of the nanolaminated films. However, the O2TR behaved differently and was only improved (up to 45 %) when carvacrol was encapsulated, i.e. nanolaminated films prepared by alternating alginate with nanocapsules of zein-carvacrol layers showed better oxygen barrier properties than those prepared as an emulsion of chitosan and carvacrol. These films containing zein-carvacrol nanocapsules also showed the highest antifungal activity (30 %), which did not significantly differ from those obtained with the highest amount of carvacrol, probably due to the controlled release of the active agent (carvacrol) from the zein-carvacrol nanocapsules. Thus, this work shows that nanolaminated films prepared with alternating layers of alginate and zein-carvacrol nanocapsules can be considered to improve the shelf-life of foodstuffs.

Magnetoliposomes based on manganese ferrite nanoparticles as nanocarriers for antitumor drugs

Manganese ferrite nanoparticles with a size distribution of 26 ± 7 nm (from TEM measurements) were synthesized by the coprecipitation method. The obtained nanoparticles exhibit a superparamagnetic behaviour at room temperature with a magnetic squareness of 0.016 and a coercivity field of 6.3 Oe. These nanoparticles were either entrapped in liposomes (aqueous magnetoliposomes, AMLs) or covered with a lipid bilayer, forming solid magnetoliposomes (SMLs). Both types of magnetoliposomes, exhibiting sizes below or around 150 nm, were found to be suitable for biomedical applications. Membrane fusion between magnetoliposomes (both AMLS and SMLs) and GUVs (giant unilamellar vesicles), the latter used as models of cell membranes, was confirmed by F¨orster Resonance Energy Transfer (FRET) assays, using a NBD labeled lipid as the energy donor and Nile Red or rhodamine B-DOPE as the energy acceptor. A potential antitumor thienopyridine derivative was successfully incorporated into both aqueous and solid magnetoliposomes, pointing to a promising application of these systems in oncological therapy, simultaneously as hyperthermia agents and nanocarriers for antitumor drugs.

Synthesis of new peptide derivatives that self-assemble into nanostructured hydrogels for biomedical applications

Tese de Doutoramento em Ciências (área de especialização em Química)

Development and characterization of lipid-based nanosystems for controlled release of bioactive compounds

Tese de Doutoramento em Engenharia Química e Biológica.

Presence of starch enhances in vitro biodegradation and biocompatibility of a gentamicin delivery formulation

The effect of α-amylase degradation on the release of gentamicin from starch-conjugated chitosan microparticles was investigated up to 60 days. Scanning electron microscopic observations showed an increase in the porosity and surface roughness of the microparticles as well as reduced diameters. This was confirmed by 67% weight loss of the microparticles in the presence of α-amylase. Over time, a highly porous matrix was obtained leading to increased permeability and increased water uptake with possible diffusion of gentamicin. Indeed, a faster release of gentamicin was observed with α-amylase. Starch-conjugated chitosan particles are non-toxic and highly biocompatible for an osteoblast (SaOs-2) and fibroblast (L929) cell line as well as adipose-derived stem cells. When differently produced starch-conjugated chitosan particles were tested, their cytotoxic effect on SaOs-2 cells was found to be dependent on the crosslinking agent and on the amount of starch used.

Development of Janus hydrogel microcapsules as novel biomaterials-stem cells construct for 3D co-culture applications

Co-cultures of two or more cell types and biodegradable biomaterials of natural origin have been successfully combined to recreate tissue microenvironments. Segregated co-cultures are preferred over conventional mixed ones in order to better control the degree of homotypic and heterotypic interactions. Hydrogel-based systems in particular, have gained much attention to mimic tissue-specific microenvironments and they can be microengineered by innovative bottom-up approaches such as microfluidics. In this study, we developed bi-compartmentalized (Janus) hydrogel microcapsules of methacrylated hyaluronic acid (MeHA)/methacrylated-chitosan (MeCht) blended with marine-origin collagen by droplet-based microfluidics co-flow. Human adipose stem cells (hASCs) and microvascular endothelial cells (hMVECs) were co-encapsulated to create platforms of study relevant for vascularized bone tissue engineering. A specially designed Janus-droplet generator chip was used to fabricate the microcapsules (<250â μm units) and Janus-gradient co-cultures of hASCs: hMVECs were generated in various ratios (90:10; 75:25; 50:50; 25:75; 10:90), through an automated microfluidic flow controller (Elveflow microfluidics system). Such monodisperse 3D co-culture systems were optimized regarding cell number and culture media specific for concomitant maintenance of both phenotypes to establish effective cell-cell (homotypic and heterotypic) and cell-materials interactions. Cellular parameters such as viability, matrix deposition, mineralization and hMVECs re-organization in tube-like structures, were enhanced by blending MeHA/MeCht with marine-origin collagen and increasing hASCs: hMVECs co-culture gradient had significant impact on it. Such Janus hybrid hydrogel microcapsules can be used as a platform to investigate biomaterials interactions with distinct combined cell populations.

Semipermeable capsules wrapping a multifunctional and self-regulated co-culture microenvironment for osteogenic differentiation

A new concept of semipermeable reservoirs containing co-cultures of cells and supporting microparticles is presented, inspired by the multi-phenotypic cellular environment of bone. Based on the deconstruction of the â stem cell nicheâ , the developed capsules are designed to drive a self-regulated osteogenesis. PLLA microparticles functionalized with collagen I, and a co-culture of adipose stem (ASCs) and endothelial (ECs) cells are immobilized in spherical liquified capsules. The capsules are coated with multilayers of poly(L-lysine), alginate, and chitosan nano-assembled through layer-by-layer. Capsules encapsulating ASCs alone or in a co-culture with ECs are cultured in endothelial medium with or without osteogenic differentiation factors. Results show that osteogenesis is enhanced by the co-encapsulation, which occurs even in the absence of differentiation factors. These findings are supported by an increased ALP activity and matrix mineralization, osteopontin detection, and the up regulation of BMP-2, RUNX2 and BSP. The liquified co-capsules also act as a VEGF and BMP-2 cytokines release system. The proposed liquified capsules might be a valuable injectable self-regulated system for bone regeneration employing highly translational cell sources.

Marine origin polysaccharides in drug delivery systems

Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine.