Search

Los ácidos grasos trans son más perjudiciales desde el punto de vista nutricional que los ácidos grasos saturados. Una ingesta excesiva de grasa trans afecta principalmente al sistema cardiovascular, aumentando la incidencia de cáncer y otras patologías. En 2004, Dinamarca y Canadá lideraron la limitación de su contenido en alimentos al 2% sobre grasa total. Otra medida adoptada fue la obligatoriedad de incluir información sobre grasa trans en el etiquetado, propuesta por la Food and Drug Administration (FDA) de EE. UU. a partir de 2006. En 2015, La FDA prohibió uso de aceites parcialmente hidrogenados, principal fuente de los ácidos grasos trans de origen industrial. En 2019, la Comisión Europea finalmente restringió el contenido de grasa trans de origen industrial en alimentos del 2%, sobre grasa total. Aún existen regiones en países del Este Europeo, antiguas repúblicas soviéticas, zonas asiáticas (India y Pakistán) y gran parte de África donde se detectan cifras muy altas y preocupantes de grasa trans en alimentos procesados, debido a la falta de regulaciones efectivas. La Organización Mundial de la Salud (OMS) está implementando el programa REPLACE para eliminar el uso de la grasa trans a nivel mundial. En este trabajo se analizaron margarinas españolas reformuladas (“cero trans”) que presentaban niveles de grasa trans inferiores al 0,5%, sobre grasa total. Se empleó el método de análisis de infrarrojos ATR-FTIR (-2D) de segunda derivada, el cual se demostró ser más rápido, eficaz y sencillo que el método de cromatografía de gases. Antes de las reformulaciones, la carga de grasa trans en margarinas era muy alta en países como Canadá, Estados Unidos o Países Bajos. Se evaluaron también varios productos tradicionalmente ricos en grasa trans (dónuts, galletas, snacks, palomitas de maíz, sopas deshidratadas y alimentos de comida rápida), encontrando que los niveles de grasa trans eran inferiores al 1% sobre la grasa total, excepto en los casos de las palomitas de m, From a nutritional point of view, trans-fatty acids are even more harmful than saturated fatty acids. Excessive intake of trans fat primarily affects the cardiovascular system, increasing the incidence of cancer and other pathologies. In 2004, Denmark and Canada led the way in limiting trans-fat content in food to 2% of total fat. Another measure implemented was the mandatory inclusion of trans fat information on labeling, proposed by the U.S. Food and Drug Administration (FDA) starting in 2006. In 2015, the FDA banned the use of partially hydrogenated oils, the main source of industrially produced trans fatty acids. In 2019, the European Commission finally restricted industrial trans-fat content in food to 2% of total fat. There are still regions in Eastern European countries, former Soviet republics, Asian areas (India and Pakistan), and much of Africa where very high and concerning levels of trans fat in processed foods are reported due to ineffective regulations. The World Health Organization (WHO) is implementing the REPLACE program to eliminate trans fat use globally. In this study, reformulated Spanish margarines ("zero trans") were analyzed, showing trans-fat levels below 0.5% of total fat. The second derivative ATR-FTIR (-2D) infrared analysis method was used, proving to be faster, more effective, and simpler than gas chromatography. Prior to the reformulations, the trans-fat content in margarines was very high in countries like Canada, the United States, or the Netherlands. Various products traditionally high in trans-fat (doughnuts, biscuits, snacks, popcorn, dried soups, and fast food) were also evaluated, revealing that trans-fat levels were below 1% of total fat, except for cases like McDonald's popcorn and French fries, which ranged from 1.1% to 2%. In no instance did they exceed the legal limit of 2%. Out of the 23 samples of edible vegetable oils analyzed (olive, sunflower, corn), only 7 provided information on quality and authenticity indices (acid

An increase in resistance to key antibiotics has made the need for novel treatments for the gastric colonization of Helicobacter pylori (H. pylori) a matter of the utmost urgency. Recent studies tackling this topic have focused either on the discovery of new compounds to ameliorate therapeutic regimes (such as vonoprazan) or the synthesis of gastroretentive drug delivery systems (GRDDSs) to improve the pharmacokinetics of oral formulations. The use of semi-interpenetrating polymer networks (semi-IPNs) that can act as super-porous hydrogels for this purpose is proposed in the present work, specifically those displaying low ecological footprint, easy synthesis, self-floating properties, high encapsulation efficiency for drugs such as amoxicillin (AMOX), great mucoadhesiveness, and optimal mechanical strength when exposed to stomach-like fluids. To achieve such systems, biodegradable synthetic copolymers containing acid-labile monomers were prepared and interpenetrated with guar gum (GG) in a one-pot polymerization process based on thiol-ene click reactions. The resulting matrices were characterized by SEM, GPC, TGA, NMR, and rheology studies, and the acidic hydrolysis of the acid-sensitive polymers was also studied. Results confirm that some of the obtained matrices are expected to perform optimally as GRDDSs for the sustained release of active pharmaceutical ingredients at the gastrointestinal level, being a priori facilitated by its disaggregation. Therefore, the optimal performance of these systems is assessed by varying the molar ratio of the labile monomer in the matrices.

Antimicrobial resistance is a global concern, far from being resolved. The need of new drugs against new targets is imminent. In this work, we present a family of aminoalkyl resveratrol derivatives with antibacterial activity inspired by the properties of cationic amphipathic antimicrobial peptides. Surprisingly, the newly designed molecules display modest activity against aerobically growing bacteria but show surprisingly good antimicrobial activity against anaerobic bacteria (Gram-negative and Gram-positive) suggesting specificity towards this bacterial group. Preliminary studies into the action mechanism suggest that activity takes place at the membrane level, while no cross-resistance with traditional antibiotics is observed. Actually, some good synergistic relations with existing antibiotics were found against Gram-negative pathogens. However, some cytotoxicity was observed, despite their low haemolytic activity. Our results show the importance of the balance between positively charged moieties and hydrophobicity to improve antimicrobial activity, setting the stage for the design of new drugs based on these molecules.

Chitosan (CTS) is a polysaccharide with a wide variety of applications in the biomedical field, owing to its outstanding disinfectant properties, biocompatibility and biodegradability, but with limited mechanical properties. The proposed strategy to improve CTS-based hydrogel properties in this study is the formation of a semi-interpenetrating polymer network (semi-IPN). In this way, a photo-initiated radical click reaction was proposed to obtain a synthetic polymer, whose components were included in a CTS solution, resulting in the semi-IPN network after UV illumination. Different crosslinking degrees (CD) and CTS/polymer ratios were evaluated through rheological characterization, along with an assessment of both variables based on an experimental model design, obtaining that, for every CTS/polymer ratio, intermediate values of CD (8 %) offered the best rheological properties. In addition, chemical and microstructural characterization were carried out for selected hydrogels, obtaining consistent results according to rheological characterization, as the 1/1 CTS/polymer ratio with CD 8 % hydrogel displayed the most homogeneous pore size and distribution, consequently leading to the best rheological performance.

In the era of antimicrobial resistance, the identification of new compounds with strong antimicrobial activity and the development of alternative therapies to fight drug-resistant bacteria are urgently needed. Here, we have used resveratrol, a safe and well-known plant-derived stilbene with poor antimicrobial properties, as a scaffold to design several new families of antimicrobials by adding different chemical entities at specific positions. We have characterized the mode of action of the most active compounds prepared and have examined their synergistic antibacterial activity in combination with traditional antibiotics. Some alkyl- and silyl-resveratrol derivatives show bactericidal activity against Gram-positive bacteria in the same low micromolar range of traditional antibiotics, with an original mechanism of action that combines membrane permeability activity with ionophore-related activities. No cross-resistance or antagonistic effect was observed with traditional antibiotics. Synergism was observed for some specific general-use antibiotics, such as aminoglycosides and cationic antimicrobial peptide antibiotics. No hemolytic activity was observed at the active concentrations or above, although some low toxicity against an MRC-5 cell line was noted.

La semaglutida está convirtiéndose en uno de los fármacos más eficaces para el tratamiento de la pandemia conocida con el nombre de obesidad. Esta patología crónica afecta a un gran número de personas a nivel mundial, y está en aumento desde la aparición de la COVID-19 debido a los confinamientos domiciliarios. Se ha demostrado que está relacionada con una mayor morbimortalidad en caso de padecer dicha enfermedad. Es considerada un defecto estético, muy unido a los malos hábitos de vida, más que una enfermedad metabólica, por lo que no se le presta atención debida y los fármacos actualmente comercializados no están financiados por el Sistema Nacional de Salud. Además de esto, la ausencia de guías clínicas estandarizadas a nivel sanitario convierte a la patología en un auténtico caos en su abordaje clínico. La semaglutida se utiliza comúnmente para el tratamiento de la diabetes mellitus tipo 2 pero ha demostrado tener unos perfiles adecuados de seguridad y eficacia consiguiendo reducciones de peso, perímetro abdominal, índice de masa corporal y parámetros metabólicos como la hemoglobina glicosilada, presión sistólica relacionados con el riesgo cardiovascular, haciéndola propicia para el tratamiento de la obesidad. Es un fármaco de administración subcutánea semanal, lo que favorece la adherencia terapéutica. Uno de los puntos negativos es su elevado precio y la cronicidad del tratamiento. El objetivo es evitar los eventos cardiovasculares y la cirugía bariátrica, que es la que hasta el momento cuenta con los mejores resultados, pero también con altos riesgos para el paciente. Actualmente, están apareciendo nuevos fármacos como la tirzepatida y combinaciones de la semaglutida y cagrilintida con las que se obtienen resultados equiparables al tratamiento quirúrgico.

Even though general improvement of quality of life has happened around the globe, statistics show that gastric cancer is still a very serious medical concern in some regions of the world. A big portion of malignant neoplasms that develop inside the stomach are linked to an infection of Helicobacter pylori; in fact, this pathogen has already been categorized as a group 1 carcinogen by the World Health Organization (WHO). Still, the efficacy of current anti-H. pylori therapeutic approaches is insufficient and follows a worrying decreasing trend, mainly due to an exponential increase in resistance to key antibiotics. This work analyzes the clinical and biological characteristics of this pathogen, especially its link to gastric cancer, and provides a comprehensive review of current formulation trends for H. pylori eradication. Research effort has focused both on the discovery of new combinations of chemicals that function as optimized antibiotic regimens, and on the preparation of gastroretentive drug delivery systems (GRDDSs) to improve overall pharmacokinetics. Regarding the last topic, this review aims to summarize the latest trend in amoxicillin-loaded GRDDS, since this is the antibiotic that has shown the least bacterial resistance worldwide. It is expected that the current work could provide some insight into the importance of innovative options to combat this microorganism. Therefore, this review can inspire new research strategies in the development of efficient formulations for the treatment of this infection and the consequent prevention of gastric cancer.

El cáncer es una enfermedad que está presente en nuestras vidas casi a diario: familiares o conocidos que la padecen, noticias en la que lo escuchamos a menudo. Sin embargo, es una patología en estudio y para la cual, hoy en día, no hay tratamiento que sea 100% seguro y eficaz, aunque sí fármacos y métodos que ayudan a paliar sus síntomas o hacerlos un poco más llevaderos. Es innegable que los radicales libres tienen un papel fundamental en el desarrollo y progresión de las células cancerígenas. Por ello, cualquier método que contribuya a disminuir su concentración en el organismo, asegurando así una reducción del estrés oxidativo, es garantía de éxito en la prevención de estas patologías. Hay que tener en cuenta que el estrés oxidativo es una de las principales causas de desarrollo de mutaciones y daños en el ADN, que puede desembocar, entre otras patologías, en el cáncer. Por ello, en los antioxidantes encontramos una puerta a la investigación de nuevos procesos de prevención y tratamiento del cáncer. Su papel en el cuerpo humano, así como su concentración en el organismo y en los nutracéuticos, son objeto de estudio. Cuando se plantea la administración como suplemento de agentes antioxidantes se ha de valorar la seguridad para el paciente, su utilidad, la ausencia de perjuicios para la salud del propio paciente y que no reste eficacia al tratamiento oncológico establecido. Por todo ello, es necesario darle la importancia que se merece a la investigación científica, ya que con financiación y el esfuerzo de muchas personas que aman la investigación podemos seguir encontrando soluciones, aunque sean paliativas, para este tipo de patologías tan agresivas., Cancer is a disease that is present in our lives almost every day: we often hear news from relatives or acquaintances who suffer from it. However, it is a pathology under study and for which, to date, there is no treatment that is 100% safe and effective, although there are drugs and methods that help alleviate its symptoms or make them a little more bearable. It is undeniable that free radicals play a fundamental role in the development and progression of cancer cells. Therefore, any method that contributes to reducing its concentration in the body, thus ensuring a reduction in oxidative stress, is a guarantee of success in the prevention of these pathologies. It must be considered that oxidative stress is one of the main causes of the development of mutations and DNA damage, which can lead, among other pathologies, to cancer. Therefore, in antioxidants we find a window of opportunity to discover new processes for the prevention and treatment of cancer. Their role in the human body is being studied, as well as their optimal concentration in the body and in nutraceuticals. When considering the administration of antioxidant agents as a complement, it should be evaluated the safety for the patient, their suitability, the absence of harm to the health and that it does not undermine the efficacy of the established cancer treatment. Therefore, it is necessary to acknowledge the importance it deserves to scientific research, since with the funding and effort of many people who love research, we can continue to find solutions, even if they are palliative, for this type of aggressive pathology.

Este Trabajo versa sobre nuevas técnicas y enfoques para el descubrimiento de nuevas moléculas bioactivas y la mejora de las ya existentes. Se debe destacar la farmacocinética (PK) de cada molécula y su proceso de absorción, distribución, metabolización, excreción y toxicidad (ADMET), así como la búsqueda para agilizar el proceso de análisis y desarrollo de nuevos fármacos. De esta manera, la Quimioinformática introdujo una rutina de búsqueda en la que se relaciona la estructura-actividad y estructura-propiedad de cada una de las moléculas bioactivas a estudiar. Como consecuencia del avance informático, surge la Quimiometría que, usando señales analíticas y datos, aporta información. A raíz del progreso en estas disciplinas y su unión con las nuevas tecnologías se abre camino al descubrimiento de mecanismos de acción de determinados compuestos que, junto con la Química Combinatoria, dan lugar a las quimiotecas. Todo esto llevó a lo denominado “Machine Learning”. Como objetivos se han planteado, entre otros, la revisión de las técnicas ya existentes, conocer los programas informáticos y metodologías disponibles para la investigación y desarrollo de fármacos, así como la evaluación del potencial científico de las distintas técnicas. Los principales resultados que se han obtenidos en esta revisión bibliográfica parten de la idea de que las propiedades ADMET juega un papel crucial en el descubrimiento de nuevos fármacos y moléculas, This work deals with new techniques and approaches for the discovery of new bioactive molecules and the improvement of existing ones. The pharmacokinetics (PK) of each molecule and its process of absorption, distribution, metabolization, excretion and toxicity (ADMET) should be highlighted, as well as the search to speed up the process of analysis and development of new drugs. In this way, Chemoinformatics introduced a search routine in which the structure-activity and structure-property of each of the bioactive molecules to be studied are related. Because of the computer science advance, Chemometrics arises and, using analytical signals and data, provides valuable information. As a result of the progress in these disciplines and their union with new technologies, the way is opened to the discovery of mechanisms of action of certain 2 compounds that, together with Combinatorial Chemistry, give rise to chemotheques. All this led to what is called "Machine Learning". The objectives have been set, being one of the main ones the review of existing techniques, the exploration the computer programs and methodologies available for research and development of drugs, as well as the evaluation of the scientific potential of the different techniques. The main results obtained in this scientific literature revision are based on the idea that ADMET properties plays a crucial role in the discovery of new drugs and molecules

Thiomers (or thiolated polymers) have broken through as avant-garde approaches in anticancer therapy. Their distinguished reactivity and properties, closely linked to their final applications, justify the extensive research conducted on their preparation and use as smart drug-delivery systems (DDSs). Multiple studies have demonstrated that thiomer-rich nanoformulations can overcome major drawbacks found when administering diverse active pharmaceutical ingredients (APIs), especially in cancer therapy. This work focuses on providing a complete and concise review of the synthetic tools available to thiolate cationic and anionic polymers, in particular chitosan (CTS) and hyaluronic acid (HA), respectively, drawing attention to the most successful procedures. Their chemical reactivity and most relevant properties regarding their use in anticancer formulations are also discussed. In addition, a variety of NP formation procedures are outlined, as well as their use in cancer therapy, particularly for taxanes and siRNA. It is expected that the current work could clarify the main synthetic strategies available, with their scope and drawbacks, as well as provide some insight into thiomer chemistry. Therefore, this review can inspire new research strategies in the development of efficient formulations for the treatment of cancer.

Composting could be a suitable solution to the correct treatment and hygienization of several organic waste, producing compost that can be used in agriculture. The evolution and maturity of this process has been studied using a variety of techniques. One very promising technique for these studies is thermogravimetric analysis. On the other hand, the compost can be used for a variety of purposes different to the agricultural one, such as direct energy by combustion or energy and products by pyrolysis and its suitability can be measured by thermogravimetric techniques. With these goals, a bibliographic analysis has been done, applying Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA methodology, to the use of thermogravimetric equipment applied to the study of composting and compost uses. According to the methodology for PRISMA systematic reviews, the following databases have been searched Google Scholar, Web of Science, Mendeley, Microsoft Academic, World Wide Science, Science Direct, IEEE Xplore, Springer Link, Scopus, and PubMed by using the terms “thermogravimetry AND (compost OR composting) AND NOT plastic”.

La administración oral de macromoléculas hidrofílicas, como pueden ser los péptidos, se ha convertido en un desafío debido a la escasa absorción intestinal y su degradación en el intestino por las diversas proteasas de los sistemas enzimáticos presentes en él.Para conseguir una buena absorción de los fármacos y que el principio activo permanezca un tiempo razonable para que pueda ejercer acción local o sistémica se han desarrollado unos sistemas transportadores de fármacos basados en los tiómeros.Este trabajo se centra en las estrategias sintéticas para la obtención de tiómeros, bien sean de naturaleza catiónica o aniónica, así como en el estudio de las propiedades más importantes que presentan. Entre estas propiedades destacan su capacidad mucoadhesiva, donde el polímero interacciona con la mucina formando enlaces disulfuro y otros tipos de interacciones que determinan su bioadhesión. Otras de sus propiedades características son la capacidad de gelificación in situ de algunos de estos sistemas, la capacidad de mejorar la permeación de fármacos a través de mucosas y la inhibición de bomba de eflujo, propiedades todas ellas que permiten el diseño de diferentes formas de liberación controlada del fármacos basadas en este tipo de polímeros.Se ha abordado igualmente las diferentes vías y formas de administración de fármacos en los que los sistemas basados en tiómeros están implicados. Entre ellas destacan la vía nasal, vía ocular y la vía oral. Por último se detallan algunas otras aplicaciones de este tipo de polímeros como son aplicaciones biomédicas en el diagnostico de enfermedades y en medicina regenerativa de tejidos, así como en productoscosméticos., Oral administration of hydrophilic macromolecules, such as peptides, has become a challenge due to poor intestinal absorption and its degradation in the intestine by the various proteases of the enzymatic systems present in it.In order to achieve a good absorption of the drugs and the permanent active ingredient for a reasonable time so that it can act locally or systematically, drug transport systems treated in thiomers have been developed.This work focuses on synthetic strategies for obtaining thiomers, either cationic or anionic nature, as well as the study of the most important properties they present. These properties include its mucoadhesive capacity, where the polymer interacts with mucin forming disulfide bonds and other types of interactions that determine its bioadhesion. Other of its characteristic properties are the in situ gelation capacity of some of these systems, the ability to improve drug permeation through mucosa and the inhibition of the flow pump, all properties that allow the design of different forms of controlled release of the drug based on this type of polymers.The different routes and forms of drug administration in which the systems affected in thiomers are involved have also been addressed. These include the nasal route, the ocular route and the oral route. Finally, some other applications of this type of polymers are detailed, such as biomedical applications in the diagnosis of diseases and in regenerative tissue medicine, as well as in cosmetic products.

Life expectancy in Andalusia and in Spain has grown steadily over the past 20 years and, in 2017, they were around 86 and 80 years for women and men, respectively. This trend is the same as that observed in other developed countries. However, despite the large investments made in the fight against many diseases, the quality of life of our elders is still not optimal. Biomedical research has long focused on the synthesis and discovery of innovative drugs to treat various diseases. However, and surprisingly, the main difficulties encountered in achieving effective treatment are not related in many cases to the availability of drugs, but to the finding suitable vehicles for the release of medications in damaged organs or tissues. The Doctoral Thesis presented herein deals with the preparation of polymer systems for the development of biomaterials for advanced therapies. These include nanoparticles and nano- and micro-structured materials sensitive to changes in pH and temperature for the inclusion of lipophilic or hydrophilic molecules with therapeutic utility, for example in cancer therapy and diseases of the gastrointestinal tract. It will also proceed to the development of smart materials and matrices derived from chitosan and locust bean gum that will exhibit dynamic behaviors in biological media in line with their final use. Regarding the preparation, a battery of synthetic tools will be used: from living polymerization methods such as atom transfer radical polymerization to click chemistry. The stimulus responsive properties will be provided by the presence of covalent dynamic bonds such as Diels-Alder and acetal bonds as well as by ionic bonds. The loading of molecules with therapeutic relevance, and their release under controlled conditions will also be part of the present study. Lastly, an eco-friendly and compatible method with physiological environments for the synthesis of multifunctional and stimulus-sensitive polymeric materials will be optimized., La esperanza de vida en Andalucía y en España ha crecido de manera constante durante los últimos 20 años y, en 2017, presentaron valores cercanos a 86 y 80 años para mujeres y hombres, respectivamente. Esta tendencia es la misma que la observada en otros países desarrollados. Sin embargo, a pesar de las grandes inversiones que se realizan en la lucha contra muchas enfermedades, la calidad de vida de nuestros mayores sigue sin ser óptima. La investigación biomédica se ha centrado durante mucho tiempo en la síntesis y el descubrimiento de fármacos innovadores para tratar diversas enfermedades. Sin embargo y sorprendentemente, las principales dificultades encontradas para lograr un tratamiento eficaz no están relacionadas en muchos casos con la disponibilidad de fármacos, sino con el hallazgo de vehículos adecuados para la liberación de medicamentos en los órganos o tejidos dañados. La Tesis Doctoral que se presenta aborda la preparación de sistemas poliméricos para el desarrollo de biomateriales para terapias avanzadas. Entre ellos se incluyen nanopartículas y materiales nano- y micro-estructurados sensibles a cambios de pH y temperatura para la inclusión de compuestos lipofílicos o hidrófilos con utilidad terapéutica, por ejemplo, en la terapia contra el cáncer y enfermedades del tracto gastrointestinal. También se procederá al desarrollo de materiales inteligentes y matrices derivadas del quitosano y la goma de semilla de algarrobo que presentarán comportamientos dinámicos en medios biológicos en línea con su uso final. Con respecto a la preparación, se utilizará una batería de herramientas sintéticas: desde métodos de polimerización vivos como la polimerización por radicales de transferencia de átomos, hasta la química click. Las propiedades de respuesta a estímulos serán proporcionadas por la presencia de enlaces covalentes dinámicos como los enlaces Diels-Alder y acetal, así como por enlaces iónicos. La inclusión de sustancias de relevancia terapéutica, y su libe

The extensive use of oral dosage forms for the treatment of diseases may be linked to deficient pharmacokinetic properties. In some cases the drug is barely soluble; in others, the rapid transit of the formulation through the gastrointestinal tract (GIT) makes it difficult to achieve therapeutic levels in the organism; moreover, some drugs must act locally due to a gastric pathology, but the time they remain in the stomach is short. The use of formulations capable of improving all these parameters, as well as increasing the resident time in the stomach, has been the target of numerous research works, with low-density systems being the most promising and widely explored, however, there is further scope to improve these systems. There are a vast variety of polymeric materials used in low-density gastroretentive systems and a number of methods to improve the bioavailability of the drugs. This works aims to expedite the development of breakthrough approaches by providing an in-depth understanding of the polymeric materials currently used, both natural and synthetic, their properties, advantages, and drawbacks

A simple redox amphiphilic tri-block copolyurethane capable of assembling in the form of polymersome has been easily synthesized. Thus, the hydrophobic core is constituted by a central block containing multiple disulfide linkages, and the hydrophilic segments are formed by poly(ethylene glycol) methyl ether (mPEG2000). The disulfide-containing block was obtained by the reaction of commercial 2,2′-dithiodiethanol and hexamethylene diisocyanate, which was further reacted with the mentioned PEG to afford the tri-block copolymer nominated as mPEG-PDH-mPEG, in above 80% yield. This copolymer self-assembled into polymersomes of size around 130 nm by the water addition/solvent evaporation method. Different systems of doxorubicin/polymer ratios (D/P 0.5 – 3) were prepared and the drug loading (%DL) and encapsulation efficiency (%EE) were studied by visible light absorbance measurements. Systems D/P 2 and 3 showed DL up to 62% and 69%, respectively. Besides that, D/P 1 and 2 presented EE values in the order of 83%. Finally, the release of DOX in the presence of 0.01 M glutathione solutions at 37 °C, was 74.6% and 82% from D/P 3 and D/P 0.5, respectively, after 5 days of incubation. Further studies on other water-soluble drugs for the cancer treatment would be of great interest to demonstrate the high potential of these redox polymeric systems.

This study investigates the impact of dual ionic and covalent cross-links (ion-XrL and cov-XrL) on the properties of chitosan-based (CTS) hydrogels as eco-friendly drug delivery systems (DDS) for the model drug diclofenac sodium (DCNa). Citric acid and a diiodo-trehalose derivative (ITrh) were the chosen ionic and covalent cross-linker, respectively. The novel hydrogels completely disintegrated within 96 h by means of a hydrolysis process mediated by the enzyme trehalase. As far as the authors are aware, this is the first time that a trehalose derivative has been used as a covalent cross-linker in the formation of biodegradable hydrogels. The impact of CTS concentration and degree of cov-XrL on rheological parameters were examined by means of an experimental model design and marked differences were found between the materials. Hydrogels with maximum elastic properties were achieved at high CTS concentrations and high degrees of cov-XrL. DCNa-loaded formulations displayed well-controlled drug-release profiles strongly dependent on formulation composition (from 17% to 40% in 72 h). Surprisingly, higher degrees of covalent cross-linking led to a boost in drug release. The formulations presented herein provides a simple and straightforward pathway to design fully biodegradable, tailor-made controlled drug delivery systems with improved rheological properties.

Oxidative stress is known to be a key factor in many neurodegenerative diseases. Inflammation also plays a relevant role in a myriad of pathologies such as diabetes and atherosclerosis. Polyphenols coming from dietary sources, such as pterostilbene, may be beneficial in this type of diseases. However, most of them are rapidly metabolized and excreted, yielding very low phenolic bioavailability what makes it difficult to find out which are the mechanisms responsible for the observed bioactivity. Herein, we evaluate the effects of pterostilbene and its metabolites against H2O2-induced cell damage in human neuroblastoma SH-SY5Y cells and against lipopolysaccharide (LPS)-challenged RAW 264.7 macrophages. Among the metabolites tested, 3-methyl-4′-glucuronate-resveratrol (also called 4′-glucuronate pinostilbene, PIN-GlcAc, 11) prevented neuronal death via attenuation of reactive oxygen species (ROS) levels and increased REDOX activity in neurons. This compound is also able to ameliorate LPS-mediated inflammation on macrophages via inhibition of IL-6 and NO production. Thus, polyphenol from dietary sources could be part of potential functional foods designed to ameliorate the onset and progression of certain neurodegenerative diseases via oxidative stress reduction.

Iminosugars are carbohydrate mimetics that constitute the main group of oligosaccharide processing enzyme inhibitors. They play an important role in cell-cell recognition processes, thereby presenting a wide range of potential therapeutic applications. In this work, we present the first examples of glycopolymers containing five-membered iminosugars. The preparation is carried out by constructing first a biocompatible water-soluble and pH-responsive 2-hydroxyethyl methacrylate (HEMA)-based copolymer by RAFT polymerization with an excellent control on the copolymer composition and low polydispersity (Mn = 19,800; Mw = 23,800; Mw/ Mn = 1.2; experimental copolymer mole composition (by 1 H NMR): pHEMA49%-co-pDMAEMA51%). One-pot azidation of its primary hydroxyl groups by Mitsunobu reaction led to a full functionalization of the HEMA residues. Subsequently, a selection of alkynyl pyrrolidine iminosugars showing glycosidase inhibition properties, were anchored to the functionalized azido-polymer through CuAAC click reaction furnishing successfully the aimed water-soluble glycopolymers, which were then subjected to biological evaluation as enzyme inhibitors.

In the present work, we demonstrate the preparation of chitosan-based composites as vehicles of the natural occurring multi-drug resveratrol (RES). Such systems are endowed with potential therapeutic effects on inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis, through the sustained colonic release of RES from long-lasting mucoadhesive drug depots. The loading of RES into nanoparticles (NPs) was optimized regarding two independent variables: RES/polymer ratio, and temperature. Twenty experiments were carried out and a Box–Behnken experimental design was used to evaluate the significance of these independent variables related to encapsulation efficiency (EE). The enhanced RES EE values were achieved in 24 h at 39 °C and at RES/polymer ratio of 0.75:1 w/w. Sizes and polydispersities of the optimized NPs were studied by dynamic light scattering (DLS). Chitosan (CTS) dispersions containing the RES-loaded NPs were ionically gelled with tricarballylic acid to yield CTS-NPs composites. Macro- and microscopic features (morphology and porosity studied by SEM and spreadability), thermal stability (studied by TGA), and release kinetics of the RES-loaded CTS-NPs were investigated. Release patterns in simulated colon conditions for 48 h displayed significant differences between the NPs (final cumulative drug release: 79–81%), and the CTS-NPs composites (29–34%).

Los nanoconjugados poliméricos surgen en la interfaz de la química de los polímeros, la biología celular y las ciencias biomédicas. Las investigaciones llevadas a cabo en este campo condujeron al desarrollo de las primeras nanomedicinas basadas en polímeros. Estos conjugados poliméricos, en concreto los conjugados polímero-fármaco son solubles en agua, están diseñados para la administración parenteral y son considerados como "nuevas entidades químicas" ya que el agente bioactivo (fármaco) está unido covalentemente al portador polimérico, en lugar de estar atrapado dentro de un complejo. La terapia de polímeros se sitúa como una opción de terapia dirigida que pretende aumentar la especificidad de los tratamientos farmacológicos, es por ello que durante las últimas décadas se han desarrollado numerosos estudios que proponen el uso de estos conjugados polímerofármaco como nanotransportadores para terapias anticancerígenas. Además del aumento de la especificidad, que disminuye los efectos secundarios de estas terapias, mejora la solubilidad de fármacos hidrófobos como el paclitaxel y el docetaxel, permitiendo su entrada en la célula tumoral. Estas nanoconstrucciones son tan interesantes porque aprovechan la fisiopatología tumoral para entrar a la célula por endocitosis, y allí las enzimas lisosómicas se encargan de romper el enlace covalente, dejando libre el fármaco en el interior celular donde ejercerá su acción. En los últimos 40 años se han estado desarrollando estudios de esta novedosa terapéutica de polímeros que ha crecido exponencialmente dando lugar a más de 25 productos con licencia para uso humano como fármacos poliméricos, conjugados y como agentes de imagen.

The experimental model design proposed herein has proved to be an indispensable tool to rapidly and easily elucidate the optimal polymerization conditions in the preparation of tailor-made responsive materials for biomedical applications. The use of reversible covalent bonds for the synthesis of new materials provides the polymer structures with novel functionalities and applications. The Diels–Alder (DA) reaction is an ideal synthetic method for the preparation of functional and responsive biomaterials under mild and undemanding conditions. The present work details the optimization of the polymerization conditions to synthesize two families of thermo-sensitive polymers, with either reduction-responsive properties or enhanced hydrophilicity. These polymers have been successfully prepared from two functional bisdiene monomers: a difurfuryl dithiodiethanol derivative (DiT-Fur, 1) and a difurfuryl-dithiothreitol derivative (DTT-Fur, 2), respectively, using the same bismaleimide (DMDOO, 3) derived from triethylene glycol in both systems. Twenty experiments were conducted and a Box–Behnken experimental design was used to evaluate the importance of temperature and the water content in terms of the polymer molecular weights (Mn, determined by 1H NMR). In addition, the progress of the polymerizations at selected times was accurately monitored via IR spectroscopy. Higher temperatures were discarded since previous thermo-lability studies demonstrated that the retro-DA reaction could occur at temperatures as low as 50 °C. Temperature proved to be the most influential variable in the final Mn, exerting opposite effects in both systems. We envision that this experimental approach, applied to other polymerization processes, can enlighten the influence of key parameters in the final product obtained.

Recently, we studied glucose-nucleobase pairs, a binding motif found in aminoglycoside-RNA recognition. DNA duplexes with glucose as a nucleobase were able to hybridize and were selective for purines. They were less stable than natural DNA but still fit well on regular B-DNA. These results opened up the possible use of glucose as a non-aromatic DNA base mimic. Here, we have studied the incorporation and thermal stability of glucose with different types of anchoring units and alternative apolar sugar-nucleobase pairs. When we explored butanetriol instead of glycerol as a wider anchoring unit, we did not gain duplex thermal stability. This result confirmed the necessity of a more conformationally restricted linker to increase the overall duplex stability. Permethylated glucose-nucleobase pairs showed similar stability to glucoside-nucleobase pairs but no selectivity for a specific nucleobase, possibly due to the absence of hydrogen bonds between them. The three-dimensional structure of the duplex solved by NMR located both, the hydrophobic permethylated glucose and the nucleobase, inside the DNA helix as in the case of glucose-nucleobase pairs. Quantum chemical calculations on glucose-nucleobase pairs indicate that the attachment of the sugar to the DNA skeleton through the OH1 or OH4 positions yields the highest binding energies. Moreover, glucose was very selective for guanine when attached through OH1 or OH4 to the DNA. Finally, we examined DNA polymerase insertion of nucleotides in front of the saccharide unit. KF- polymerase from E. coli inserted A and G opposite glc and 6dglc with low efficiency but notable selectivity. It is even capable of extending the new pair although its efficiency depended on the DNA sequence. In contrast, Bst 2.0, SIII and BIOTAQ™ DNA polymerases seem to display a loop-out mechanism possibly due to the flexible glycerol linker used instead of deoxyribose.

The present work deals with the synthesis of micro-structured biomaterials based on chitosan (CTS) for their applications as biocompatible carriers of drugs and bioactive compounds. Twelve dispersions were prepared by means of functional cross-linking with tricarballylic acid (TCA); they were characterized by Fourier transform infrared spectroscopy (FT-IR), modulated temperature differential scanning calorimetry (MTDSC) and scanning electron microscopy (SEM), and their rheological properties were studied. To the best of the authors’ knowledge, no study has been carried out on the influence of CTS concentration, degree of cross-linking and drug loading on chitosan hydrogels for drug delivery systems (DDS) and is investigated herein for the first time. The influence of dispersion composition (polymer concentration and degree of cross-linking) revealed to exert a marked impact on its rheological properties, going from liquid-like to viscoelastic gels. The release profiles of a model drug, diclofenac sodium (DCNa), as well as their relationships with polymer concentration, drug loading and degree of cross-linking were evaluated. Similar to the findings on rheological properties, a wide range of release profiles was encountered. These formulations were found to display a well-controlled drug release strongly dependent on the formulation composition. Cumulative drug release under physiological conditions for 96 h ranged from 8% to 67%. For comparative purpose, Voltaren emulgel® from Novartis Pharmaceuticals was also investigated and the latter was the formulation with the highest cumulative drug release (85%). Some formulations showed similar spreadability values to the commercial hydrogel. The comparative study of three batches confirmed the reproducibility of the method, leading to systems particularly suitable for their use as drug carriers.

Micelles are good devices for use as controlled drug delivery systems because they exhibit the ability to protect the encapsulated substance from the routes of degradation until they reach the site of action. The present work assesses loading kinetics of a hydrophobic drug, pilocarpine, in polymeric micellar nanoparticles (NPs) and its pH-dependent release in hydrophilic environments. The trigger pH stimulus, pH 5.5, was the value encountered in damaged tissues in solid tumors. The new nanoparticles were prepared from an amphiphilic block copolymer, [(HEMA19%- DMA31%)-(FMA5%-DEA45%)]. For the present research, three systems were validated, two of them with cross-linked cores and the other without chemical stabilization. A comparison of their loading kinetics and release profiles is discussed, with the support of additional data obtained by scanning electron microscopy and dynamic light scattering. The drug was loaded into the NPs within the first minutes; the load was dependent on the degree of cross-linking. All of the systems experienced a boost in drug release at acidic pH, ranging from 50 to 80% within the first 48 h. NPs with the highest degree (20%) of core cross-linking delivered the highest percentage of drug at fixed times. The studied systems exhibited fine-tuned sustained release features, which may provide a continuous delivery of the drug at specific acidic locations, thereby diminishing side effects and increasing therapeutic rates. Hence, the studied NPs proved to behave as smart controlled drug delivery systems capable of responding to changes in pH.

In recent years, the preparation of valuable drug delivery systems (DDS) from self-assembled amphiphilic copolymers has attracted much attention since these nanomaterials provide new opportunities to solve problems such as the lack of solubility in water of lipophilic drugs, improve their bioavailability, prolong their circulation time and decrease the side effects associated with their administration. In the current study two types of biocompatible pH-responsive nanoparticles derived from poly(2-hydroxyethyl methacrylate) (pHEMA) have been used as drug nano-carriers, being one of them core cross-linked to circumvent their instability upon dilution in human fluids. The present paper deals with the optimization of the loading process of the labile, hydrophobic and highly active anticancer drug, Camptothecin (CPT) into the nanoparticles with regard to four independent variables: CPT/polymer ratio, sonication, temperature and loading time. Forty experiments were carried out and a Box–Behnken experimental design was used to evaluate the significance of the independent variables related to encapsulation efficiency and drug retention capacity. The enhanced drug loading and encapsulation efficiency values (58% and > 92%, respectively) of CPT were achieved by the core cross-linked NPs in 2 h at 32 °C at CPT/ polymer ratio 1.5:1 w/w and 14 min of sonication. The optimized CPT-loaded NPs were studied by dynamic light scattering and scanning electron microscopy, and an increase in size of the loaded-NP compared to the unloaded counterparts was found. Other twenty experiments were conducted to study the enability to retain CPT into the conjugates at different ionic strength values and times. The stability studies demonstrated that the core crosslinked nanocarriers displayed an excellent drug retention capacity (> 90%) at 25 °C for 15 days in every ionicstrength environments whereas the non-cross-linked ones were more stable at physiological ionic strength. The optimized systems

Micelles are excellent devices to be used as controlled drug delivery systems since they exhibit the ability to protect the drug or encapsulated substance from the routes of degradation until they reach the site of action: moreover, they can pass through biological barriers and reach intracellular compartments. In addition, when a drug is administered and released from the dosage form, the kinetic behavior of the drug depends largely on their chemical structure. However, when the drug is immersed at the core of a NP, the physicochemical properties that actually affect the distribution of the drug in the body are those from the latter. As a result, this approach controls drug release, diminishing side effects and increasing therapeutic rates. In the present work novel smart micelles have been prepared and tested as drug delivery systems

Desde hace años se estudian nuevas técnicas para mejorar el cumplimiento de los tratamientos farmacológicos; es así como surgen los sistemas de liberación controlada de fármacos. Estos sistemas tienen como objetivo liberar el fármaco en el sitio correcto, en la dosis correcta y durante el periodo de tiempo adecuado. Se construyen a partir de una serie de materiales denominados materiales inteligentes los cuales son capaces de reaccionar a un estímulo externo y proporcionar una respuesta a dicho estímulo. Se han estudiado muchos tipos de materiales para este uso pero, sin duda, los más interesantes son los conocidos como materiales con memoria de forma cuyo efecto memoria consiste en una relación causas-efecto. Se ha visto que los polímeros son buenos materiales inteligentes ya que sufren cambios físicos o químicos reversibles en respuesta a cambios en el medio ambiente tales como temperatura, pH, luz, campo eléctrico, campo magnético, etc. Esta revisión bibliográfica se centra en los distintos tipos de polímeros que existen en función del material polimérico utilizado, del tipo de respuesta que proporcionan y del estímulo al que responden. Estos presenta una serie de ventajas e inconvenientes y no todos pueden ser usados sino que deben cumplir unos criterios de seguridad para poder ser útiles como agentes transportadores de fármacos. Aunque actualmente ya existen numerosas terapias que utilizan los sistemas de liberación controlada de fármacos basándose en polímeros inteligentes, sobretodo terapias contra el cáncer, aún hay muchos estudios e investigaciones en marcha para desarrollar nuevas técnicas y nuevos tratamientos que utilicen este tipo de sistemas.

The present work describes the preparation of stable organic nanoparticles with potential use as “smart” drug delivery systems capable of encapsulating lipophilic molecules to exert their therapeutic action under the appropriate stimulus. A well-defined self-assembly hydrophilichydrophobic di-block copolymer has been synthesized via atom transfer radical polymerization (ATRP). The hydrophilic block is based on a random copolymer with DMA and HEMA units, while the hydrophobic component is a linear random copolymer of DEA and FMA. Stabilization of the nanoparticles by means of core cross-linking is addressed by Diels-Alder reactions between the furan rings of the hydrophobic blocks and the synthesized bisdienophiles; the influence of both the cross-linking agent and the degree of cross-linking in the process is discussed. The incorporation of a therapeutic agent (pilocarpine) and a lipophilic fluorescent molecule (pyrene) is evaluated. When pyrene was immersed into the micelles, there was a significant boost of the fluorescence emission (from 10- to 40-fold), due to the hydrophobic environment of the inner part of the nanoparticles. Pilocarpine is also able to be encapsulated by the prepared systems. Drug release is triggered by a reduction in the pH of the media and is strongly dependent on the degree of cross-linking achieved.

Actualmente existen numerosas enfermedades que ponen en peligro la salud de la población y en paralelo, han entrado en juego distintas estrategias terapéuticas para combatirlas. Como en numerosas ocasiones, la naturaleza ha servido de inspiración: dado que la respuesta a estímulos es un proceso básico de los sistemas vivos, se han diseñado materiales que respondan a estímulos externos como son cambios en la temperatura, el pH, la luz, el campo eléctrico, la presencia o no de determinados productos químicos y la fuerza iónica. Estas respuestas se manifiestan en cambios drásticos, como por ejemplo, modificaciones en las características de superficie, solubilidad, auto-ensamblaje molecular o transiciones gel-sol. Este fascinante comportamiento “estímulo-respuesta” presente en los polímeros “inteligentes” ha impulsado el desarrollo de nuevas aplicaciones en distintos campos como la biomedicina. Así, se están estudiando en profundidad las aplicaciones de dichos materiales en la vectorización terapéutica, la ingeniería de tejidos, sensores etc. y numerosos artículos y patentes evidencian el rápido progreso en este área (Ferris y cols., 2014; Jeong, Gutowska, 2002; Ma, Tian, 2014; Roy y cols., 2013). El objetivo científico-técnico que se plantea en esta Memoria es la preparación de polímeros con interés, como biomateriales en biomedicina y farmacia, mediante síntesis total a partir de monómeros comerciales fácilmente asequibles para la formación de sistemas de liberación de fármacos vectorizados y sensibles a estímulos externos. Se estudiará el auto-ensamblaje de los mismos en nanopartículas capaces de incorporar moléculas pequeñas o agentes terapéuticos. Se trata, por tanto, de un trabajo que proyecta la obtención de suspensiones de nanopartículas orgánicas capaces de transportar cantidades suficientes de fármacos para ejercer su acción terapéutica bajo el estímulo adecuado.

La presente invención se refiere a conjugados del chitosan (o sus derivados) con tiolactonas (síntesis y estructuras químicas), en las composiciones cosméticas, biomédicas-farmacéuticas que contienen dichos conjugados, y a sus aplicaciones, que presentan las siguientes propiedades: no tóxicos, biodegradables, con excelentes propiedades de mucoadhesión, cohesión e inhibición enzimática, con propiedades mejoradas de permeabilidad, captación celular y gran estabilidad como agentes de recubrimiento de cánulas y otros dispositivos médicos y como sistemas transportadores de fármacos, esto es, con largos tiempos de permanencia de los principios activos englobados, lo que garantiza un excelente control en la liberación de los fármacos incluidos en la formulación y además, capaces de gelificar en presencia de oxígeno.

The efficient, controlled polymerization of a batch of new poly(hydroxyethyl methacrylate-co-furfuryl methacrylate)s, [poly(HEMA-co-FMA)], of various compositions was achieved using atom transfer radical polymerization (ATRP) in methanol. When the FMA composition did not exceed the 10 mol% ratio, the evolution of molecular weight with conversion was linear, and polydispersities were around 1.1 for polymerization reactions at 15 °C and around 1.3-1.4 at 25 °C, indicating good control over the polymerization process. HEMA-based hydrogels were obtained by means of the Diels-Alder reaction between poly(HEMA-co-FMA) and an hydrophilic bisdienophile. Gelification was monitored by diffusion-filtered 1H NMR and solution 1H NMR spectroscopy. Modulated temperature differential scanning calorimetry (MTDSC) suggests the thermo-reversibility of the Diels-Alder coupling reaction of HEMA polymeric networks. Rheological studies showed that the linear viscoelasticity functions of hydrogels were influenced by the chemical composition.

A batch of linear [m,n]-type sugar-based polyureas was synthesized by polyaddition reaction in solution from hexamethylene diisocyanate or 4,4’-methylene-bis(phenyl isocyanate) with the acyclic 2,3,4-tri-O-methyl-1,5- diamino-alditols having L-arabino, or xylo confi guration or the bicyclic 1,6-diamino-1,6-dideoxy-2,4:3,5-diO-methylene-D-glucitol. The polymers were obtained in good yields and fair molecular weights. All these polyureas were semicrystalline materials showing well-defi ned melting transition within the 86−171°C range, with Tg s being dependent on the aliphatic or aromatic nature of the diisocyanate used, and on the cyclic or acyclic chemical structure of the sugar moiety. They were found to be stable up to around 240°C, decomposing at higher temperatures through a one- or two-stage mechanism.

Las nuevas normativas que la Legislación impone relativas a los hábitos saludables y de seguridad que deben cumplirse en los laboratorios, han supuesto una revolución muy positiva en estos entornos de trabajo. Estos cambios están siendo posibles, gracias a la introducción de mejores infraestructuras, que están posibilitando al investigador la integración en su trabajo de nuevas maneras de trabajar, encaminadas a minimizar tanto los riesgos de accidentes como el impacto de sus investigaciones en el medioambiente. Las normas que se exponen a continuación han sido elaboradas por la Comisión de Prevención de Riesgos del Departamento de Química Orgánica y Farmacéutica, de la Facultad de Farmacia de Sevilla, con objeto de ser de seguidas por todos sus miembros. Estas normas son completamente extrapolables a cualquier laboratorio de entorno químico, en el que convivan por un lado disolventes orgánicos o inorgánicos y reactivos químicos, y por otro, personal altamente cualificado o de nueva incorporación a este tipo de entornos. El documento se divide en varias partes: 1) Normas de obligado cumplimiento, 2) Recomendaciones, y 3) Formulario de aceptación de las Normas de Trabajo anteriores.

La industria de los polímeros comenzó a desarrollarse en el siglo XIX basándose en la modificación de ciertos polímeros naturales, por ejemplo, algunos hidratos de carbono como el almidón, la celulosa y la caseína, que fueron finalmente sustituidos por ot