Síntesis, caracterización y aplicaciones de nanotransportadores formados por tensioactivos derivados de (Ru(bpy)3)2+.

En la presente Tesis Doctoral se han sintetizado cuatro metalosurfactantes derivados del Ru(bpy)3 2+, donde se han variado el número de cadenas hidrofóbicas y la longitud de las mismas. Se han caracterizado los tensioactivos y se ha estudiado su proceso de agregación. Posteriormente se ha investigado la interacción entre los monómeros y los agregados de los metalosurfactantes con el ADN, al que compactan, pasando de una conformación elongada a una forma de ovillo. Se han determinado las constantes de interacción entre los metalosurfactantes y las α-, β., y -ciclodextrinas. Se observa la formación de complejos de inclusión estables, lo que permitiría usar las ciclodextrinas para decompactar el ADN. Se han preparado también metaloliposomas y se han caracterizado los complejos liposoma/ADN o lipoplejos, en los que el polinucleótido está compactado. Los estudios de viabilidad celular realizados confirman que los etalosurfactantes tienen propiedades antineoplásicas. Como monómeros, presentan baja toxicidad a concentraciones bajas, mientras que las micelas presentan citotoxicidad elevada. Sólo en el caso de los metaloliposomas se encuentra, a concentraciones intermedias, que las células sanas prácticamente no se ven afectadas, mientras que para las líneas celulares cancerígenas son citotóxicos. Estudios de internalización celular indican una elevada internalización de las metalomicelas. Por último, las metalomicelas y los metaloliposomas se han usado como nanotransportadores de un agente antineoplásico como la doxorrubicina, observándose altos porcentajes de encapsulación de este fármaco, especialmente en los liposomas

Preparation and Characterization of New Liposomes. Bactericidal Activity of Cefepime Encapsulated into Cationic Liposomes

Cefepime is an antibiotic with a broad spectrum of antimicrobial activity. However, this antibiotic has several side effects and a high degradation rate. For this reason, the preparation and characterization of new liposomes that are able to encapsulate this antibiotic seem to be an important research line in the pharmaceutical industry. Anionic and cationic liposomes were prepared and characterized. All cationic structures contained the same cationic surfactant, N,N,N-triethyl-N-(12-naphthoxydodecyl)ammonium. Results showed a better encapsulation-efficiency percentage (EE%) of cefepime in liposomes with phosphatidylcholine and cholesterol than with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). The presence of cholesterol and the quantity of egg-yolk phospholipid in the liposome increased the encapsulation percentage. The bactericidal activity against Escherichia coli of cefepime loaded into liposomes with phosphatidylcholine was measured. The inhibitory zone in an agar plate for free cefepime was similar to that obtained for loaded cefepime. The growth-rate constant of E. coli culture was also measured in working conditions. The liposome without any antibiotic exerted no influence in such a rate constant. All obtained results suggest that PC:CH:12NBr liposomes are biocompatible nanocarriers of cefepime that can be used in bacterial infections against Escherichia coli with high inhibitory activity

Binding of DNA by a dinitro-diester calix[4]arene: Denaturation and condensation of DNA

A study of a dinitro-diester calix[4]arene (5,17-(3-nitrobenzylideneamino)-11,23-di-tert-butyl-25,27-diethoxycarbonyl methyleneoxy-26,28-dihydroxycalix[4]arene) interaction with calf-thymus DNA was carried out using several techniques. The measurements were done at various molar ratios X=[calixarene]/[DNA]. Results show diverse changes in the DNA conformation depending on the X value. Thus, at low macrocycle concentrations, the calixarene binds to the polynucleotide. This interaction, mainly in groove mode, weakens the hydrogen bonds between base pairs of the helix inducing denaturation of the double strands, as well as condensation of the macromolecule, from an extended coil state to a globular state. An opposite effect is observed at X molar ratios higher than 0.07. The de-condensation of DNA happens, that is, the transition from a compact state to a more extended conformation, probably due to the stacking of calixarene molecules in the solution. Results also show the importance of making a proper choice of the system under consideration.Junta de Andalucía P08-FQM-03623, P12-FQM-110

Metallo-Liposomes Derived from the [Ru(bpy)3]2+ Complex as Nanocarriers of Therapeutic Agents

The obtaining of nanocarriers of gene material and small drugs is still an interesting research line. Side-effects produced by the toxicity of several pharmaceutics, the high concentrations needed to get therapeutic effects, or their excessive use by patients have motivated the search for new nanostructures. For these reasons, cationic metallo-liposomes composed by phosphatidylcholine (PC), cholesterol (CHO) and RuC1C19 (a surfactant derived from the metallic complex [Ru(bpy)3]2+) were prepared and characterized by using diverse techniques (zeta potential, dynamic light scattering and electronic transmission microscopy –TEM-). Unimodal or bimodal populations of spherical aggregates with small sizes were obtained depending on the composition of the liposomes. The presence of cholesterol favored the formation of small aggregates. ct-DNA was condensed in the presence of the liposomes investigated. In-vitro assays demonstrated the ability of these nanoaggregates to internalize into different cell lines. A positive gene transfection into human bone osteosarcoma epithelial cells (U2OS) was also observed. The RuC1C19 surfactant was used as sensor to quantify the binding of DNA to the liposomes. Doxorubicin was encapsulated into the metallo-liposomes, demonstrating their ability to be also used as nanocarriers of drugs. A relationship between then encapsulation percentage of the antibiotic and the composition of the aggregates has been established.Junta de Andalucía 2019/FQM-206, 2019/FQM-274Ministerio de Ciencia e Innovación RTI2018-100692-BI00, PI-0005-2018, P18-RT-127

Metallo-Liposomes of Ruthenium Used as Promising Vectors of Genetic Material

Gene therapy is a therapeutic process consisting of the transport of genetic material into cells. The design and preparation of novel carriers to transport DNA is an important research line in the medical field. Hybrid compounds such as metallo-liposomes, containing a mixture of lipids, were prepared and characterized. Cationic metal lipids derived from the [Ru(bpy)3]2+ complex, RuC11C11 or RuC19C19, both with different hydrophobic/lipophilic ratios, were mixed with the phospholipid DOPE. A relation between the size and the molar fraction α was found and a multidisciplinary study about the interaction between the metallo-liposomes and DNA was performed. The metallo-liposomes/DNA association was quantified and a relationship between Kapp and α was obtained. Techniques such as AFM, SEM, zeta potential, dynamic light scattering and agarose gel electrophoresis demonstrated the formation of lipoplexes and showed the structure of the liposomes. L/D values corresponding to the polynucleotide's condensation were estimated. In vitro assays proved the low cell toxicity of the metallo-liposomes, lower for normal cells than for cancer cell lines, and a good internalization into cells. The latter as well as the transfection measurements carried out with plasmid DNA pEGFP-C1 have demonstrated a good availability of the Ru(II)-based liposomes for being used as non-toxic nanovectors in gene therapy.España Consejería de Educación y Ciencia de la Junta de Andalucía (Proyecto de Excelencia P12-FQM-1105, FQM-206 and FQM-274, and PI-0005-2018)España,, Universidad de Sevilla, VI Plan Propio Universidad de Sevilla (PP2018-10338)España Ministerio de Ciencia, Innovación y Universidades (RTI2018-100692-B-I00

Diagnosis and Treatment in Asthma and Allergic Rhinitis: Past, Present, and Future

Respiratory diseases are pathological conditions that affect airways, hampering breathing and causing high mortality. In particular, asthma and allergic rhinitis (AR) are two of the most common airway diseases that affect millions of people and have a high prevalence in childhood and adulthood. Asthma is a heterogeneous chronic inflammatory disease characterized by wheezing, chest tightness, shortness of breath, and cough. AR occurs with rhinorrhea, nasal congestion, and sneezing. Indeed, these pathologies share common physiopathological mechanisms such as airway hyperresponsiveness and similar immunopathology such as tissue eosinophilia and T-helper type 2 inflammation. Moreover, AR can be an important risk factor for suffering asthma. Thus, early diagnosis and effective treatment are crucial to improving the health and quality of life of these patients. Classical drugs such as corticosteroids have been used; however, in the last decades, efforts to improve treatments have increased, focusing on biological agents and specific allergen immunotherapy development. Moreover, more precise diagnostic tools have been elaborated, besides classical methods (medical history, physical examination, and pulmonary function tests), such as basophil activation test, and specific cellular and molecular biomarkers (microRNAs, sputum/blood eosinophils, IgE serum, and periostin levels). Therefore, in this review, we compile all these important issues for managing asthma and AR.Espada-Sánchez M, Sáenz de Santa María R, Martín-Astorga MdC, Lebrón-Martín C, Delgado MJ, Eguiluz-Gracia I, Rondón C, Mayorga C, Torres MJ, Aranda CJ, Cañas JA. Diagnosis and Treatment in Asthma and Allergic Rhinitis: Past, Present, and Future. Applied Sciences. 2023; 13(3):1273. https://doi.org/10.3390/app1303127

Empleo de la metodología ABP en la docencia de la Universidad de Sevilla como una herramienta clave para la aplicación de la economía circular en la industria

La economía circular se está convirtiendo en uno de los conceptos más importantes en la economía mundial debido a los grandes beneficios medioambientales que presenta. No obstante, la falta de personal cualificado en esta área está provocando un gran rechazo en el sector industrial. Es por ello que la Universidad de Sevilla está incluyendo docencia dedicada a la economía circular en su formación académica. En este contexto, el objetivo de este trabajo es dar a conocer los aspectos clave de la docencia sobre economía circular llevada a cabo en la Universidad de Sevilla.Circular economy is becoming one of the most important concepts in the world economy due to the great environmental benefits it presents. However, the lack of qualified personnel in this area is causing a great rejection in the industrial sector. In this way, University of Seville is including teaching dedicated to the circular economy in its academic training. In this context, the objective of this work is to publicize the key aspects of the circular economy teaching carried out at the University of Seville

Comparativa de l'ensenyament presencial í no presencial d'assígnatures científicotecníques a la Uníversítat de Sevílla

La situación actual ha generado la necesidad de replantearse la enseñanza no presencial. No obstante, este tipo de enseñanza en carreras científico-técnicas puede tener grandes inconvenientes. Por este motivo, en este trabajo se plantea una comparativa entre la elaboración de prácticas presenciales y no presenciales en asignaturas científicas y técnicas. Así, se utilizó una metodología participativa a través de la resolución de problemas donde hubiera un aprendizaje activo de los alumnos, implantándose en Grados de la rama científica como son el Grado en Farmacia, el Doble Grado en Farmacia y Óptica y Optometría y el Grado en Química. Los resultados obtenidos demuestran que hay grandes diferencias entre las competencias adquiridas a través de prácticas presenciales y telemáticas. Aunque deja entre dicho la necesidad de presencialidad para conseguir todas las competencias esenciales en este tipo de carreras.Toe current situation has generated the need to rethink online teaching. However, this type of teaching in scientific-technical degrees can have major drawbacks. For this reason, this work presents a comparison between the preparation of classroom and non-classroom practices in scientific and technical subjects. Thus, a participatory methodology was used through the resolution of problems where the students presented an active learning, implanting in degrees of the scientific branch such as the Degree in Pharmacy, the Double Degree in Pharmacy and Optics and Optometry and the Degree in Chemistry. Toe results obtained show that there are great differences between the skills acquired through face-to-face and telematic practices. Although it leaves into question the need of presentiality to get all the essential competences in this type of degrees.La situació actual ha generat la necessitat de replantejar- se l'ensenyament no presencial. No obstant aixo, aquest tipus d'ensenyament en carreres cientificotecniques pot tenir grans inconvenients. Per aquest motiu, en aquest treball es planteja una comparativa entre l'elaboració de practiques presencials i no presencials en assignatures científiques i tecniques. Així, es va utilitzar una metodologia participativa a través de la resolució de problemes on hi hagués un aprenentatge actiu dels alumnes, implantant-se en Graus de la branca científica com són el Grau en Farmacia, el Doble Grau en Farmacia i Óptica i Optometria i el Grau en química. Els resultats obtinguts demostren que hi ha grans diferencies entre les competencies adquirides a través de practiques presencials i telematiques. Encara que deixa sense aclarir la necessitat de presencialitat per aconseguir totes les competencies essencials en aquest tipus de carreres

Potentiometric Study of Carbon Nanotube/Surfactant Interactions by Ion-Selective Electrodes. Driving Forces in the Adsorption and Dispersion Processes

The interaction (adsorption process) of commercial ionic surfactants with non-functionalized and functionalized carbon nanotubes (CNTs) has been studied by potentiometric measurements based on the use of ion-selective electrodes. The goal of this work was to investigate the role of the CNTs’ charge and structure in the CNT/surfactant interactions. Non-functionalized single- (SWCNT) and multi-walled carbon nanotubes (MWCNT), and amine functionalized SWCNT were used. The influence of the surfactant architecture on the CNT/surfactant interactions was also studied. Surfactants with different charge and hydrophobic tail length (sodium dodecyl sulfate (SDS), octyltrimethyl ammonium bromide (OTAB), dodecyltrimethyl ammonium bromide (DoTAB) and hexadecyltrimethyl ammonium bromide (CTAB)) were studied. According to the results, the adsorption process shows a cooperative character, with the hydrophobic interaction contribution playing a key role. This is made evident by the correlation between the free surfactant concentration (at a fixed [CNT]) and the critical micellar concentration, cmc, found for all the CNTs and surfactants investigated. The electrostatic interactions mainly determine the CNT dispersion, although hydrophobic interactions also contribute to this process.Junta de Andalucía-2019/FQM-206 y 2019/FQM-274Fondo Europeo de Desarrollo Regional (FEDER

Cationic Single-Chained Surfactants with a Functional Group at the End of the Hydrophobic Tail DNA Compacting Efficiency

The interaction between calf-thymus DNA, ctDNA, and various single-chained surfactants with different functional groups at the end of hydrophobic tail was studied with the goal of investigating the influence of the functional group nature on surfactant DNA compacting efficiency. The surfactants investigated were dodecyltriethylammonium bromide (DTEABr), triethyl(1-phenoxydodecyl)ammonium bromide (12PhBr), triethyl(2-naphthoxydodecyl)ammonium bromide (12NBr) and 11-(isonicotinoyloxy)-N,N,N-triethyl-1-undecanaminium bromide (11PyBr). Results made evident that the surfactants’ tendencies to self-aggregation is the key factor determining their efficiency to compact the nucleic acid. Subsequently, DOPE/12NBr/pEGFP-C1 lipoplexes, with different cationic surfactant molar fractions (α) and mass ratios (L/D), were prepared and characterized. DOPE is a zwitterionic phospholipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, and the plasmid pEGFP-C1 carries a GFP coding sequence with the necessary regulatory elements for constitutive expression of the gene in human cells. 12NBr was chosen because it was the most efficient DNA compacting agent among the surfactants investigated. Finally, the cytotoxicity and transfection efficiency (TE) of DOPE/12NBr/pDNA lipoplexes, with different compositions, were investigated.Junta de Andalucía FQM-206, FQM-274, PI-0005-2018Universidad de Sevilla PP2019/0000074