Study of the thermal degradation of bioactive sol-gel coatings for the optimization of its curing process

A set of materials has been prepared by sol-gel process containing different quantities of hydroxyapatite (0, 2.5 and 5% HAp w/w) using as silica precursors glycidyloxypropyltrimethoxysilane (GPTMS) and triethoxyvinylsilane (VTES). In order to optimize the curing process to obtain sintherized systems (inorganic network) or hybrid systems (organic&-inorganic) a TG and FTIR studies have been developed and degradation kinetic triplet parameters were obtained (the activation energy, pre-exponential factor, and function of degree of conversion). The kinetic study was analyzed by means of an integral isoconversional non-isothermal procedure (model free), and the kinetic model was determined by the Coats&-Redfern method and through the compensation effect (IKR). All the systems followed the n = 6 kinetic model. The addition of HAp increases the thermal stability of the systems. The isothermal degradation was simulated from non-isothermal data, and the curing process could be defined to obtain the two types of materials. Temperature under 250 °C allows the formation of hybrids networks.Publicad

The design and characterisation of sol–gel coatings for the controlled-release of active molecules

The controlled release of active agents from a matrix has become increasingly important for oral, transdermal or implantable therapeutic systems, due to the advantages of safety, efficacy and patient convenience. Controlled-release hybrid (organic-inorganic) sol-gel coating synthesis has been performed to create a sol with an active molecule included (procaine). Synthesis procedures included acid-catalysed hydrolysis, sol preparation, the addition of a procaine solution to the sol, and the subsequent gelation and drying. The alkoxide precursors used were triethoxyvinylsilane and tetraethyl-orthosilicate (TEOS) in molar ratios of 1:0, 9:1, 8:2 and 7:3. After the determination of the optimal synthesis parameters, the material was physicochemically characterised by silicon-29 nuclear magnetic resonance (²⁹Si-NMR) and Fourier transform infrared spectroscopy, contact angle analysis and electrochemical impedance spectroscopy tests. Finally, the materials were assayed in vitro for their ability to degrade by hydrolysis and to release procaine in a controlled manner. The sustained release of procaine over a 3-day period was demonstrated. A close correlation between release and degradation rates suggests that film degradation is the main mechanism underlying the control of release. Electrochemical analysis reveals the formation of pores and water uptake during the degradation. The quantity of TEOS is one of the principal parameters used to determine the kinetics of degradation and procaine release.The supports of the Spanish Ministry of Economy and Competitiveness through project IPT-010000-2010-004 and of the University of the Basque Country (UPV/EHU) through ‘‘UFI11/56’’ are kindly acknowledge

Análisis de la distribución de los equipamientos públicos municipales en la ciudad de Valladolid según los estándares de la Agenda Urbana Española.

La correcta localización de los equipamientos públicos en las ciudades es fundamental para conseguir desarrollar modelos que fomenten la sostenibilidad, compacidad y equilibrio en los espacios urbanos. Las potencialidades que ofrecen los SIG hacen que sea posible conocer y valorar la adecuación de los equipamientos y servicios públicos en cuanto a su localización idónea. El objetivo del presente estudio es, por tanto, determinar si es apropiado el número de equipamientos municipales básicos que se encuentran en la ciudad de Valladolid para cubrir las necesidades de sus ciudadanos. Para ello, se tomarán como base las distancias definidas por la Agenda Urbana Española, publicada en 2019, para determinar si la población se encuentra próxima a los principales equipamientos básicos, además de conocer su grado de cobertura espacial a través de la exploración de diferentes métodos de análisis espacial.Estos procedimientos, basados en la selección por localización, relacionan los equipamientos con la distancia a las secciones censales, ya sea considerando cualquiera de sus partes o referidas al centroide de cada uno de los polígonos. Al comparar ambos métodos, se ha decidido trabajar con el primero de los mencionados, basado en la distancia desde la capa fuente a las entidades de la capa de destino. Los resultados muestran que, en general, aunque con diferencias entre las dotaciones analizadas, la cobertura para el conjunto de la ciudad es adecuada en su mayoría, sobre todo en los servicios de transporte público, apropiados para favorecer el intercambio de personas entre las diferentes zonas de la ciudad. Destacan también los centros sociales, cuya función principal es facilitar la integración y el desarrollo de sus usuarios. Sin embargo, se mostrará que existen ciertas secciones que no se encuentran cubiertas por la mayoría de equipamientos, por lo que sería necesario su estudio detallado para analizar cómo a través de la implantación de las propuestas aprobadas en los presupuestos participativos se puede mejorar la dotación de esas zonas.<br /

A bicyclic α-iminophosphonate improves cognitive decline in 5xFAD murine model of neurodegeneration

I2 receptors (I2-IR) are widely distributed in the central nervous system. I2-IR ligands are associated with a neuroprotective effect but, as I2-IR structure remains unknown, the discovery of better and more selective ligands is necessary to understand the pharmacological and molecular implications of I2-IR. Recently, we described a new imidazoline-structure family which showed high affinity and selectivity for I2-IR. In vivo studies in mice indicated a neuroprotective role and revealed beneficial effects in behaviour and cognition with a murine model of neurodegeneration, senescence-accelerated prone mouse (SAMP8). Herein, we report a novel non-imidazoline-structure of bicyclic α-iminophosphonates family with high affinities for I2-IR. In vivo studies in 5X-FAD mice (a transgenic representative model of AD) and SAMP8 mice (a model of neurodegeneration linked to aging) showed an improvement in behaviour and cognition, a reduction of AD hallmarks and of neuroinflammation markers for the mice treated with the lead compound B06. After evaluating several pathways associated with neurodegeneration, we demonstrated that CaN pathway plays a critical role on the neuroprotective effects of I2-IR ligands on SAMP8 mice model. To rule out warnings of the novel family, we calculated DMPK and physicochemical properties for the novel bicyclic α-iminophosphonates. As well, we carried out drug metabolism, safety studies and in vivo pharmacokinetics for lead compound B06. In summary, we present a novel family of I2-IR ligands, its effectiveness in in vivo models and the possible neuroprotective molecular mechanism mediated by them. This highlights that the modulation of I2-IR by bicyclic α-iminophosphonates may open a new therapeutic venue for unmet neurodegenerative conditions

Bicyclic alfa-iminophosphonates as high affinity imidazoline I2 receptor ligands for Alzheimer's disease

Imidazoline I2 receptors (I2-IR), widely distributed in the CNS and altered in patients that suffered from neurodegenerative disorders, are orphan from the structural point of view and new I2-IR ligands are urgently required for improving their pharmacological characterization. We report the synthesis and 3D-QSAR studies of a new family of bicyclic α-iminophosphonates endowed with relevant affinities for human brain I2-IR. Acute treatment in mice with a selected compound significantly decreased the FADD protein in the hippocampus, a key marker in neuroprotective actions. Additionally, in vivo studies in the familial Alzheimer's disease 5xFAD murine model revealed beneficial effects in behavior and cognition. These results are supported by changes in molecular pathways related to cognitive decline and Alzheimer's disease. Therefore bicyclic α-iminophosphonates are tools that may open new therapeutic avenues for I2-IR, particularly for unmet neurodegenerative conditions

Synthesis of hybrid sol-gel materials and their biological evaluation with human mesenchymal stem cells

Surface engineering of biomaterials could promote the osseointegration of implants. In this work, two types of hybrid sol–gel materials were developed to stimulate cell attachment, proliferation and differentiation of osteogenic cells. One type was synthesised from vinyl triethoxysilane (VTES) and tetraethyl-orthosilicate (TEOS) at different molar ratios, while the other from VTES and hydroxyapatite particles (HAp). Hybrid materials were systematically investigated using nuclear magnetic resonance, Fourier transform infrared spectroscopy and contact angle metrology. The biocompatibility and osseoinduction of the coatings were evaluated by measuring mesenchymal stem cell proliferation using MTT assays and analysing the mineralised extracellular matrix production by quantifying calcium-rich deposits. The results highlighted the versatility of these coatings in obtaining different properties by changing the molar ratio of the VTES:TEOS precursors. Thus, mineralisation was stimulated by increasing TEOS content, while the addition of HAp improved cell proliferation but worsened mineralisation

Study of the thermal degradation of bioactive sol–gel coatings for the optimization of its curing process

A set of materials has been prepared by sol–gel process containing different quantities of hydroxyapatite (0, 2.5 and 5% HAp w/w) using as silica precursors glycidyloxypropyltrimethoxysilane (GPTMS) and triethoxyvinylsilane (VTES). In order to optimize the curing process to obtain sintherized systems (inorganic network) or hybrid systems (organic–inorganic) a TG and FTIR studies have been developed and degradation kinetic triplet parameters were obtained (the activation energy, pre-exponential factor, and function of degree of conversion). The kinetic study was analyzed by means of an integral isoconversional non-isothermal procedure (model free), and the kinetic model was determined by the Coats–Redfern method and through the compensation effect (IKR). All the systems followed the n = 6 kinetic model. The addition of HAp increases the thermal stability of the systems. The isothermal degradation was simulated from non-isothermal data, and the curing process could be defined to obtain the two types of materials. Temperature under 250 °C allows the formation of hybrids network

Study of the degradation of hybrid sol–gel coatings in aqueous medium

The design and development of suitable multilayered functional coatings for delaying corrosion advance in metals and become controlled-release vehicles requires that the properties of the coatings are known. Coatings prepared by the sol–gel method provide a good approach as protective layers on metallic surfaces. This kind of coating can be prepared from pure chemical reagents at room temperature and atmospheric pressure, with compositions in a very wide range of environmentally non-aggressive precursors. Sol–gel coatings based on siloxane bonded units were prepared, starting with an organic–inorganic hybrid system. Synthesis procedures included acid-catalysed hydrolysis, sol preparation, and the subsequent gelation and drying. The alkoxide precursors used were methyl-triethoxysilane (MTMOS) and tetraethyl-orthosilicate (TEOS) in molar ratios of 10:0, 9:1, 8:2 and 7:3. After determination of the optimal synthesis parameters, the materials were characterised by solid 29Si nuclear magnetic resonance (29Si NMR), Fourier transform infrared spectroscopy (FTIR), contact angle measurement and electrochemical impedance spectroscopy (EIS) test. Finally, the materials were assayed by controlling their weight in contact with water, to determine their ability to degrade by hydrolysis. Electrochemical analysis reveals the formation of pores and water uptake during the degradation. The quantity of TEOS is one of the principal parameters that determine the kinetics of degradation. There is a correlation between the degradation process obtained for long periods and the electrochemical parameters obtained by EIS in short times. The study tries to incorporate knowledge that can be used for designing the degradation process of the functional coatings and to control their properties in short times

Sex differences in the antidepressant-like response and molecular events induced by the imidazoline-2 receptor agonist CR4056 in rats

In searching for novel targets to design antidepressants, among the characterized imidazoline receptors (IR), I2 receptors are an innovative therapeutical approach since they are dysregulated in major depressive disorder and by classical antidepressant treatments. In fact, several I2 agonists have been characterized for their antidepressant-like potential, but the results in terms of efficacy were mixed and exclusively reported in male rodents. Since there are well-known sex differences in antidepressant-like efficacy, this study characterized the potential effects induced by two I2 drugs, CR4056 (i.e., most promising drug already in phase II clinical trial for its analgesic properties) and B06 (a compound from a new family of bicyclic α-iminophosphonates) under the stress of the forced-swim test in male and female rats exposed to early-life stress. Moreover, some hippocampal neuroplasticity markers related to the potential effects observed were also evaluated (i.e., FADD, p-ERK/ERK, mBDNF, cell proliferation: Ki-67 + cells). The main results replicated the only prior study reporting the efficacy of CR4056 in male rats, while providing new data on its efficacy in females, which was clearly dependent on prior early-life stress exposure. Moreover, B06 showed no antidepressant-like effects in male or female rats. Finally, CR4056 increased FADD content and decreased cell proliferation in hippocampus, without affecting p- ERK/t-ERK ratio and/or mBDNF content. Interestingly, these effects were exclusively observed in female rats, and independently of early-life conditions, suggesting some distinctive molecular underpinnings participating in the therapeutic response of CR4056 for both sexes. In conjunction, these results present CR4056 with an antidepressant-like potential, especially in female rats exposed to stress early in life, together with some neuronal correlates described in the context of these behavioral changes in females