http://hdl.handle.net/10366/4377 Thu, 30 Apr 2026 20:33:17 GMT 2026-04-30T20:33:17Z http://hdl.handle.net/10366/170168 [EN]Polydopamine has acquired great relevance in the field of nanomedicine due to its physicochemical properties. Previously, it has been reported that nanoparticles synthetized from this polymer are able to decrease the viability of breast and colon tumor cells. In addition, it is well known that the size of therapeutic particles plays an essential role in their effect. As a consequence, the influence of this parameter on the cytotoxicity of polydopamine nanoparticles was studied in this work. For this purpose, polydopamine nanoparticles with three different diameters (115, 200 and 420 nm) were synthetized and characterized. Their effect on the viability of distinct sorts of human carcinomas (breast, colon, liver and lung) and stromal cells was investigated, as well as the possible mechanisms that could be responsible for such cytotoxicity. Moreover, polydopamine nanoparticles were also loaded with doxorubicin and the therapeutic action of the resulting nanosystem was analyzed. As a result, it was demonstrated that a smaller nanoparticle size is related to a more enhanced antiproliferative activity, which may be a consequence of polydopamine’s affinity for iron ions. Smaller nanoparticles would be able to adsorb more lysosomal Fe3+ and, when they are loaded with doxorubicin, a synergistic effect can be achieved. Tue, 29 Oct 2019 00:00:00 GMT http://hdl.handle.net/10366/170168 2019-10-29T00:00:00Z http://hdl.handle.net/10366/169845 [ES] El tratamiento de aguas residuales es un problema continuo en la sociedad. A medida que avanza la tecnología y la industria, las aguas residuales son cada vez más abundantes y complejas de tratar y la legislación cada más estricta y exigente en términos de la presencia de contaminantes en fluido acuosos. Para solucionar este problema se aplican cada vez más tratamientos avanzados pero que actualmente son caros de aplicar (por ejemplo, la osmosis inversa), o tienen desventajas que los hacen poco prácticos, por lo que siempre se buscan nuevas opciones más sostenibles. Las partículas magnéticas tienen características que les proporcionan varias ventajas para su utilización en el tratamiento de aguas: debido a sus propiedades superficiales y porosas se pueden utilizar como adsorbentes en procesos de adsorción; de igual modo, las partículas magnéticas con hierro en su superficie pueden servir de catalizador en procesos de Fenton heterogéneo, procesos que oxidan compuestos orgánicos y otros contaminantes por medio de especies reactivas de oxígeno que se generan in situ. Por otro lado, como presentan importantes propiedades magnéticas se pueden separar o controlar a través de campos magnéticos, lo que permite la utilización de un proceso sencillo (separación magnética) para lograr la recuperación de estas partículas y, después de regenerarlas, su reutilización. En esta Tesis Doctoral se ha investigado de forma más profundizada la eficacia de la aplicación de las partículas magnéticas en el tratamiento de aguas, incluyendo su recuperación, regeneración y reutilización y un estudio de la influencia de las principales variables. Para tal, se estudiaron varios tipos de partículas magnéticas para su utilización en procesos de adsorción, Fenton heterogéneo y Foto-Fenton heterogéneo: micropartículas de magnetita, nanopartículas de magnetita y de hematita, hierro cerovalente, y nanohilos de hierro. Con relación a los efluentes estudiados, se han utilizado efluentes conteniendo colorantes textiles, azúcares, aguas residuales de EDAR, lixiviados de CTR, y aguas conteniendo fenoles. También, se han mejorado métodos y procesos, incluyendo analíticos, de forma a poderse proporcionar al futuro investigador del campo una más eficaz y rápida obtención y evaluación de los resultados logrados. También es importante indicar que se desarrolló un método de regeneración para las partículas recuperadas, de forma que mantengan su eficacia cuando sean sucesivamente reutilizadas en tratamientos. El método de regeneración utilizado resulta eficaz, con micropartículas regeneradas con hidracina siendo capaces de eliminar más del 70% de Azul de Metileno presente en el agua por medio de Fenton heterogéneo, incluso cuando las mismas partículas han sido reutilizadas 10 veces. Por comparación, partículas sin regenerar reducen su eficacia al 40% en el segundo uso, y por debajo del 20% en el tercer uso y sucesivos. Por otro lado, el proceso de Foto- Fenton heterogéneo muestra una capacidad de autoregeneración gracias al uso de luz ultravioleta, con las mismas partículas siendo capaces de eliminar más del 95% del Azul de Metileno presente durante 10 usos aun cuando solo han sido regeneradas una única vez al principio de todo el proceso antes de ser utilizadas. Se han estudiado otros métodos diferentes de regeneración y reactivos. En todos los experimentos en los que se ha utilizado un valor óptimo para las variables principales (determinado en esta Tesis por series de secuencias de experimentos) se han logrado obtener eficacias de reducción de contaminantes elevadas, llegando en muchos de los casos a superar, como mínimo, los 90%. Como ejemplo de uno de los muchos resultados obtenidos se puede por ejemplo destacar que a la hora de tratar aguas residuales reales, 2.5 g/L de nanopartículas de magnetita son capaces de reducir el TOC un 80%, comparado con la misma cantidad de micropartículas reduciendo el TOC solo un 20%. Cuando se tratan aguas con compuestos fenólicos, 0.5 g/L de nanopartículas de magnetita eliminan más del 98% de fenoles, mientras que concentraciones superiores de micropartículas solo eliminan alrededor del 40%.; [EN] Wastewater treatment is a permanent problem in society. As technology and industries advance, wastewater becomes increasingly abundant and complex to treat, and legislation becomes more stringent and demanding regarding the presence of contaminants in aqueous fluids. To solve this problem, advanced treatments are increasingly being applied, but they are currently expensive (e.g., reverse osmosis) or have disadvantages that make them impractical, so new, more sustainable options are constantly being sought. Magnetic particles have characteristics that provide several advantages for use in water treatment: due to their surface and porous properties, they can be used as adsorbents in adsorption processes; similarly, magnetic particles with iron on their surface can serve as catalysts in heterogeneous Fenton processes, processes that oxidize organic compounds and other contaminants through the generation of reactive oxygen species. On the other hand, since they have important magnetic properties, they can be separated or controlled by magnetic fields, which allows for the use of a simple and gentle process (magnetic separation) achieving the recovery of these particles and, after regenerating them, allowing their reuse. They can be used as adsorbents in adsorption processes; and particles with iron on their surface can serve as catalysts for heterogeneous Fenton processes, processes that can oxidize organic compounds by means of reactive oxygen species. This PhD Thesis has investigated in greater depth the effectiveness of the application of magnetic particles in water treatment, including their recovery, regeneration, and reuse, and a study of the influence of the main variables. To this end, several types of magnetic particles were studied for use in adsorption processes, heterogeneous Fenton and heterogeneous photo-Fenton: magnetite microparticles, magnetite and hematite and zero-valent iron nanoparticles, and iron nanowires. Regarding the effluents studied, effluents containing textile dyes, sugars, wastewater from WWTPs, leachates from waste treatment plants, and water containing phenols were used. Also, methods and processes, including analytical ones, have been improved to provide future researchers in the field with more efficient and rapid acquisition and evaluation of the results achieved. In addition, it is also important to notice that a regeneration method was developed for the recovered particles, ensuring their effectiveness is maintained when they are subsequently reused in the treatment process. The regeneration method used is effective, with microparticles regenerated with hydrazine capable of removing more than 70% of the methylene blue present in water using heterogeneous Fenton, even when the same particles have been reused 10 times. By comparison, unregenerated particles reduce their effectiveness to 40% on the second use, and below 20% on the third and subsequent uses. Furthermore, the heterogeneous photo-Fenton process demonstrates a self-regenerative capacity thanks to the use of ultraviolet light, with the same particles capable of removing more than 95% of the methylene blue present during 10 uses, even when they have only been regenerated once at the beginning of the entire process before being used. Other regeneration methods and reagents have been studied. In all experiments using an optimal value for the main variables (determined in this thesis by a series of sequences of experiments), high pollutant reduction efficiencies have been achieved, in many cases reaching at least 90%. As an example of one of the many results obtained, it can be highlighted that when treating real wastewater, 2.5 g/L of magnetite nanoparticles are able to reduce TOC by 80%, compared to the same amount of microparticles, which reduces TOC by only 20%. When treating water with phenolic compounds, 0.5 g/L of magnetite nanoparticles removes more than 98% of phenols, while higher concentrations of microparticles only remove around 40%.; [PT] O tratamento de águas residuais é um problema permanente na sociedade. À medida que a tecnologia e a indústria avançam, as águas residuais tornam-se cada vez mais abundantes e complexas de tratar, e a legislação torna-se mais rigorosa e exigente quanto à presença de contaminantes nos fluidos aquosos. Para resolver este problema, os tratamentos avançados estão a ser cada vez mais aplicados, mas atualmente são dispendiosos (por exemplo, osmose inversa) ou apresentam desvantagens que os tornam impraticáveis, pelo que se procuram constantemente novas opções mais sustentáveis. As partículas magnéticas apresentam características que proporcionam diversas vantagens para utilização no tratamento de águas: devido às suas propriedades superficiais e porosas, podem ser utilizadas como adsorventes em processos de adsorção; da mesma forma, partículas magnéticas com ferro na superfície podem servir como catalisadores em processos Fenton heterogéneos, processos que oxidam compostos orgânicos e outros contaminantes através da geração de espécies reativas de oxigénio. Por outro lado, como possuem propriedades magnéticas importantes, podem ser separadas ou controladas por campos magnéticos, o que permite a utilização de um processo gentil (separação magnética). A separação magnética é um processo simples para obter a recuperação simples destas partículas e, após a sua regeneração, para a sua reutilização. Nesta tese de doutoramento investigou-se em maior profundidade a eficácia da aplicação de partículas magnéticas no tratamento de águas, incluindo a sua recuperação, regeneração e reutilização, e um estudo da influência das principais variáveis. Para tal, foram estudados vários tipos de partículas magnéticas para utilização em processos de adsorção, Fenton heterogéneo e foto-Fenton heterogéneo: micropartículas de magnetita, nanopartículas de magnetita e hematita, nanopartículas de ferro zerovalente e nano-fios de ferro. Relativamente aos efluentes estudados, foram utilizados efluentes contendo corantes têxteis, açúcares, águas residuais de ETAR, lixiviados de estações de tratamento de resíduos sólidos urbanos e águas contendo fenóis. Além disso, os métodos e processos, incluindo os analíticos, foram melhorados para proporcionar aos futuros investigadores da área uma aquisição e avaliação mais eficiente e rápida dos resultados obtidos. Por outro lado, é importante salientar que foi desenvolvido um método de regeneração para as partículas recuperadas, garantindo a manutenção da sua eficácia quando posteriormente reutilizadas no processo de tratamento. O método de regeneração utilizado é eficaz, com micropartículas regeneradas com hidrazina capazes de remover mais de 70% do azul de metileno presente na água utilizando Fenton heterogéneo, mesmo quando as mesmas partículas foram reutilizadas 10 vezes. Em comparação, as partículas não regeneradas reduzem a sua eficácia para 40% na segunda utilização e para menos de 20% na terceira e seguintes utilizações. Além disso, o processo foto-Fenton heterogéneo demonstra capacidade auto-regeneradora graças à utilização de luz ultravioleta, com as mesmas partículas capazes de remover mais de 95% do azul de metileno presente durante 10 utilizações, mesmo quando regeneradas apenas uma vez no início de todo o processo antes de serem utilizadas. Outros métodos e reagentes de regeneração têm sido estudados. Em todas as experiências, utilizando um valor ótimo para as principais variáveis (determinado nesta tese por uma série de sequências de experiências), foram alcançadas elevadas eficiências de redução de poluentes, em muitos casos excedendo pelo menos os 90%. Como exemplo de um dos muitos resultados obtidos, pode-se destacar que, no tratamento de águas residuais reais, 2,5 g/L de nanopartículas de magnetita são capazes de reduzir o COT em 80%, em comparação com a mesma quantidade de micropartículas, que reduz o COT em apenas 20%. No tratamento de água com compostos fenólicos, 0,5 g/L de nanopartículas de magnetita removem mais de 98% dos fenóis, enquanto concentrações mais elevadas de micropartículas removem apenas cerca de 40%.; [FR] Le traitement des eaux usées est un problème constant pour la société. Avec les progrès technologiques et industriels, les eaux usées deviennent de plus en plus abondantes et complexes à traiter, et la législation se durcit quant à la présence de contaminants dans les fluides aqueux. Pour résoudre ce problème, des traitements avancés sont de plus en plus utilisés, mais ils sont actuellement coûteux (par exemple, l'osmose inverse) ou présentent des inconvénients qui les rendent peu pratiques. De nouvelles options plus durables sont donc constamment recherchées. Les particules magnétiques présentent des caractéristiques qui offrent plusieurs avantages pour le traitement de l'eau : grâce à leur surface et à leurs propriétés poreuses, elles peuvent être utilisées comme adsorbants dans les procédés d'adsorption ; de même, les particules magnétiques contenant du fer à leur surface peuvent servir de catalyseurs dans les procédés hétérogènes de Fenton, qui oxydent les composés organiques et autres contaminants par la génération d'espèces réactives de l'oxygène. D'autre part, grâce à leurs propriétés magnétiques importantes, elles peuvent être séparées ou contrôlées par des champs magnétiques, ce qui permet un procédé doux (séparation magnétique). La séparation magnétique est un procédé simple permettant de récupérer ces particules et, après régénération, de les réutiliser. Elles peuvent être utilisées comme adsorbants dans les procédés d'adsorption ; les particules ferreuses peuvent servir de catalyseurs pour les procédés de Fenton hétérogène, procédés permettant d'oxyder des composés organiques par des espèces réactives de l'oxygène. Cette thèse de doctorat a approfondi l'efficacité de l'application des particules magnétiques au traitement de l'eau, notamment leur récupération, leur régénération et leur réutilisation, ainsi que l'étude de l'influence des principales variables. À cette fin, plusieurs types de particules magnétiques ont été étudiés pour leur utilisation dans les procédés d'adsorption, le Fenton hétérogène et le photo-Fenton hétérogène : microparticules de magnétite, magnétite et hématite, nanoparticules de fer zérovalentes et nanofils de fer. Les effluents étudiés ont porté sur des effluents contenant des colorants textiles, des sucres, des eaux usées de stations d'épuration, des lixiviats de stations de traitement de residues solide, et des eaux contenant des phénols. De plus, les méthodes et procédés, notamment analytiques, ont été améliorés afin de permettre aux futurs chercheurs du domaine une acquisition et une évaluation plus efficaces et plus rapides des résultats obtenus. De plus, il est important de noter qu'une méthode de régénération des particules récupérées a été développée, garantissant ainsi leur efficacité lors de leur réutilisation ultérieure dans le processus de traitement. La méthode de régénération utilisée est efficace : les microparticules régénérées à l'hydrazine sont capables d'éliminer plus de 70 % du bleu de méthylène présent dans l'eau avec du Fenton hétérogène, même après dix réutilisations. En comparaison, les particules non régénérées réduisent leur efficacité à 40 % lors de la deuxième utilisation, et à moins de 20 % lors de la troisième utilisation et des suivantes. De plus, le procédé photo-Fenton hétérogène démontre une capacité d'auto-régénération grâce à l'utilisation de la lumière ultraviolette : les mêmes particules sont capables d'éliminer plus de 95 % du bleu de méthylène présent lors de dix utilisations, même après une seule régénération au début du processus. D'autres méthodes et réactifs de régénération ont été étudiés. Dans toutes les expériences utilisant une valeur optimale pour les variables principales (déterminée dans cette thèse par une série d'expériences), des rendements élevés de réduction des polluants ont été obtenus, dépassant souvent au moins 90 %. À titre d'exemple, parmi les nombreux résultats obtenus, on peut souligner que lors du traitement des eaux usées réelles, 2,5 g/L de nanoparticules de magnétite permettent de réduire le COT de 80 %, contre seulement 20 % pour la même quantité de microparticules. Lors du traitement de l'eau avec des composés phénoliques, 0,5 g/L de nanoparticules de magnétite élimine plus de 98 % des phénols, tandis que des concentrations plus élevées de microparticules n'en éliminent qu'environ 40 %. Wed, 01 Jan 2025 00:00:00 GMT http://hdl.handle.net/10366/169845 2025-01-01T00:00:00Z http://hdl.handle.net/10366/169278 [EN]Polydopamine (PD) is a synthetic melanin analogue of growing importance in the eld of biomedicine, especially with respect to cancer research, due, in part, to its biocompatibility. But little is known about the cytotoxic e ects of PD on cancer cell lines. PD is a UV-vis absorbing material whose absorbance overlaps with that of formazan salts, which are used to assess cell viability in MTT assays. In this study, a protocol has been established to eliminate the contributing absorbance of PD at 550 nm, and has been applied to characterize the cytotoxicity of PD nanoparticles in both healthy and breast cancer cell lines. Once the protocol is applied, it was found that PD is per se an antineoplastic system, meaning it selectively kills cancer cells, especially those of breast cancer, but it has no toxic effect on healthy cells. The mechanism of action could be related to the production of ROS and the alteration of iron homeostasis in lysosomes. To the best of our knowledge there are only a few examples of nanoparticle systems devoid of drugs that selectively kill cancer cells. Mon, 08 Oct 2018 00:00:00 GMT http://hdl.handle.net/10366/169278 2018-10-08T00:00:00Z http://hdl.handle.net/10366/169275 [EN]Polydopamine (PD) is a synthetic melanin pigment of great importance in biomedicine, where its affinity for metallic cations, especially paramagnetic ions, has sparked interest in its use in the development of magnetic resonance imaging (MRI) contrast agents. In this work, we report the cytotoxicity of metal-enriched PD nanoparticles on NIH3T3, a healthy cell line and BT474, a breast cancer cell line. Remarkably, it was found that the metal- enriched PD particles (Mn+ = Fe3+, Fe2+ and Cu2+) were highly cytotoxic to the breast cancer cells, even after 24 h of treatment. Although, this effect was not selective systems, since an acute cytotoxic effect was also observed on the healthy cell line, this system can be considered as starting point for designing advanced antineoplastic agents. Sun, 01 Jul 2018 00:00:00 GMT http://hdl.handle.net/10366/169275 2018-07-01T00:00:00Z http://hdl.handle.net/10366/169109 In the last decade, novel strategies to synthesize polydopamine nanoparticles (PDA NPs) have been continuously developed owing to the applications of this synthetic melanin analog in nanotechnology. However, producing them on a large scale continues to be a challenge and, to achieve this purpose, the ability to control and predict PDA NP size and morphology is essential. For this reason, in this work, the formation kinetics of PDA NPs produced by dopamine oxidative polymerization were analyzed as a function of the alkalinity degree (ammonium hydroxide concentration) and the type of alcohol (ethanol or 2-propanol) used in the synthesis medium. It was found that PDA NPs underwent nucleation/growth during polymerization, and a simple mathematical model was proposed to predict PDA NP diameter depending on the reaction time and the alkalinity degree. Moreover, with the aim of optimizing the reaction time without altering the main physicochemical properties, PDA NPs obtained after four different times (1, 3, 5 and 24 hours) were characterized. It was shown that reducing the PDA NP synthesis time from 24 to 3 hours was possible without altering either their Fe3+-chelation capacity or their antineoplastic activity, which are two of the properties that make them a revelant material for nanomedicine studies. Sat, 01 Jan 2022 00:00:00 GMT http://hdl.handle.net/10366/169109 2022-01-01T00:00:00Z http://hdl.handle.net/10366/169108 Despite the advances made in the fight against HER2-positive breast cancer, the need for less toxic therapies and strategies that avoid the apparition of resistances is indisputable. For this reason, a targeted nanovehicle for paclitaxel and trastuzumab, used in the first-line treatment of this subtype of breast cancer, had already been developed in a previous study. It yielded good results in vitro but, with the aim of further reducing paclitaxel effective dose and its side effects, a novel drug delivery system was prepared in this work. Thus, polydopamine nanoparticles, which are gaining popularity in cancer nanomedicine, were novelty loaded with paclitaxel and trastuzumab. The effectiveness and selectivity of the nanoparticles obtained were validated in vitro with different HER2-overexpressing tumor and stromal cell lines. These nanoparticles showed more remarkable antitumor activity than the nanosystem previously designed and, in addition, to affect stromal cell viability rate less than the parent drug. Moreover, loaded polydopamine nanoparticles, which notably increased the number of apoptotic HER2-positive breast cancer cells after treatment, also maintained an efficient antineoplastic effect when validated in tumor spheroids. Thereby, these bioinspired nanoparticles charged with both trastuzumab and paclitaxel may represent an excellent approach to improve current HER2-positive breast cancer therapies. Fri, 01 Jan 2021 00:00:00 GMT http://hdl.handle.net/10366/169108 2021-01-01T00:00:00Z http://hdl.handle.net/10366/169107 Currently, one of the bottlenecks in the large-scale production of particles used for biomedical purposes is reproducibility achieving sizes less than 100 nm. For this reason, the main purpose of this work was to elucidate how the size of polydopamine nanoparticles (PDA NPs), which are widely used in cancer nanomedicine, was affected by several synthesis parameters to facilitate their production scaling-up. Specifically, PDA NPs growth kinetics were investigated as a function of the polymerization temperature (15–50 ◦C) and the type of alcohol (ethanol, 2-propanol, or a mixture of both) used to produce them, finding that an increase in temperature and the amount of 2-propanol in the solvent media allowed smaller NPs to be obtained. Based on the results achieved, a mathematical model capable of predicting PDA NP diameter as a function of the temperature and reaction time, the NH4OH concentration, and the type of alcohol used to synthesize them was proposed. Also, PDA solubility in the different media was studied to explain NP size behavior depending on the type of alcohol employed, which conditioned the formation of PDA oligomers. Finally, additional assays were conducted to confirm that an increase in the synthesis temperature did not affect some of the most important properties of PDA NPs from a biomedical point of view: their Fe3+-loading capacity and their inherent antitumor activity. Therefore, the results obtained in this research could be useful to scale-up the obtaining of 100 nm PDA NPs in a reproducible manner hereafter without significantly altering their outstanding physical-chemical properties. Mon, 01 Jan 2024 00:00:00 GMT http://hdl.handle.net/10366/169107 2024-01-01T00:00:00Z http://hdl.handle.net/10366/169106 Despite all prevention programs, many cases of colorectal cancer (CRC) are diagnosed when they have already metastasized. Herein, chemotherapy is required, and combination of 5-fluorouracil, irinotecan, and leucovorin (FOLFIRI) is one of the first-line treatments chosen. However, it is so toxic that compromises patient outcomes. Thus, with the aim of improving FOLFIRI pharmacokinetics while reducing its side effects, the three compounds that make it up were simultaneously absorbed in this work into polydopamine nanoparticles (PDA NPs), also loaded with an antibody to target CRC cells overexpressing the epithermal growth factor receptor (EGFR). All adsorptions, which were successfully executed without toxic solvents, were electrostatic in nature according to the calorimetry results obtained. Otherwise, based on the experiments done, 5-flurouracil, irinotecan, and leucovorin release from PDA NPs followed a burst-like pattern, which was possibly mediated by Fickian diffusion mechanisms. Finally, the assays performed with two EGFR-overexpressing CRC cell lines showed that the uptake of the nanosystem was rapid, and that its therapeutic effect was very significant. It managed to greatly reduce the viability of these cells to 22–30% after 72 h of incubation. Furthermore, when tumor spheroids were developed and treated with PDA NPs loaded with FOLFIRI and the anti-EGFR antibody (FOLFIRI-CTX@PDA NPs), these demonstrated to continue to have very marked therapeutic activity. In addition, FOLFIRI-CTX@PDA NPs affected to a lesser extent the survival rate of stromal cells, with which viability experiments were also done. Therefore, the novel developed PDA nanocarrier could be a promising strategy to enhance metastatic CRC therapy hereafter. Mon, 01 Jan 2024 00:00:00 GMT http://hdl.handle.net/10366/169106 2024-01-01T00:00:00Z http://hdl.handle.net/10366/167070 [EN] In recent years, interest in nanomedicine, particularly in the use of polymeric nanoparticles, has grown significantly as an innovative and effective strategy for cancer treatment. Although conventional chemotherapy has proven to be effective, it presents significant limitations, such as systemic toxicity, lack of specificity, and the occurrence of adverse reactions. In this context, nanomedicine offers a promising alternative by enabling targeted drug delivery through nanoparticles (NPs), minimizing damage to healthy tissues, reducing multidrug resistance, and facilitating treatment personalization. In this regard, the present thesis investigates the feasibility of using polydopamine nanoparticles (PDA NPs), a type of polymeric NPs, for cancer detection and treatment, aiming to enhance therapeutic efficacy while minimizing systemic adverse effects. Despite promising results in preclinical studies, challenges remain regarding large-scale production, protein corona formation, and potential toxicity, which must be addressed before clinical application. Therefore, this investigation focuses on the synthesis, characterization, optimization, and validation of PDA NP-based drug delivery systems for the treatment of metastatic colorectal cancer and HER-2 positive breast cancer, with an emphasis on biocompatibility and tumor specificity. Wed, 01 Jan 2025 00:00:00 GMT http://hdl.handle.net/10366/167070 2025-01-01T00:00:00Z http://hdl.handle.net/10366/166865 [EN] Currently, new cancer treatment options are being developed following tumor resection surgery, with a focus on minimizing invasiveness and reducing systemic toxicity to lower the risk of recurrence. In this context, the thermosensitive poloxamer Pluronic Acid F-127 (PF-127) is modified by incorporating polysaccharides with varying structures—xanthan gum (XG), alginate (ALG), gellan gum (GG), and levan (LEV). Hydrogels are synthesized using different ratios of polysaccharides and PF-127. Rheological results reveal that adding polysaccharides to the hydrogel matrix increases storage moduli from 8 to 11–18 kPa and viscosity from 4.5 to 6.1–7.1 Pa s. Additionally, the micellar aggregation capacity (MAC) and gelation temperature shift from 34 °C to between 22 and 31 °C. Studies on 5-fluorouracil (5-FU) release from these composites indicate that enhanced MAC prolongs drug release 4 times longer compared to the hydrogel made with PF-127 alone. A mathematical model is applied to analyze these experimental results, taking into account polymer chain release. Hydrogel’s degradation rate and viscosity are primary determinants of drug release duration. Thus, by modifying the hydrogel composition, MAC, thermosensitivity, and drug release profile can be finely controlled based on the polysaccharide used. Wed, 01 Jan 2025 00:00:00 GMT http://hdl.handle.net/10366/166865 2025-01-01T00:00:00Z http://hdl.handle.net/10366/166757 [EN] Alginate–gelatin coacervation has been studied by considering different experimental parameters, such as gelatin preheating, pH, alginate–gelatin ratio and their respective concentrations, and salt effect. Results were assessed in terms of size and polydispersion via dynamic light scattering, electrostatic charge in the surface by zeta potential measurements, electrostatic interaction forces by static light scattering, stability by turbidimetry and viscoelastic and pseudoplastic behavior by rheology (oscillatory and statistical analysis). According to the results, gelatin structure has to be previously modified to induce the proper interactions with a subsequent pH reduction. Specifically, stable coacervates (according to turbidimetry and dynamic light scattering) with a size of 300–600 nm and a polydispersion lower than 0.25 were obtained after preheating the gelatin at 37 C and with a subsequent pH reduction until 4–5 for an alginate–gelatin ratio between 1:4 and 1:6. However, different experimental conditions promote an unsuccessful coacervation, obtaining always precipitates and/or coacervates with a wider particle size distribution. Furthermore, in order to study the effect of the temperature on the coacervates, different cooling–heating cycles were applied on them over a week, showing the stability of the thermo-reversible coacervates for almost 5 days. Also, the interactions were characterized via static light scattering, analyzing the second virial coefficient. Moreover, rheological oscillatory results can be used to identify a proper coacervation due to the increase of the storage modulus. However, no significant changes were observed with statistical analysis due to the highly diluted character of the precursor solutions. These results highlighted how a proper combination of different experimental conditions, mainly temperature to promote a partial gelatin unraveling as well as pH reduction, is required to successfully produce coacervates. Finally, salt effect was proven to induce precipitation when NaCl was increasingly added to solutions of stable coacervates. Mon, 01 Jan 2024 00:00:00 GMT http://hdl.handle.net/10366/166757 2024-01-01T00:00:00Z http://hdl.handle.net/10366/166638 [EN] Dishwashing is a daily task performed by millions of people, either manually or with the help of cleaning appliances. Automatic dishwashers are specifically designed for this purpose and are used in both domestic and commercial settings. The efficiency of ADWs is attributed to the distribution of various stages in the washing cycle, appropriate temperature settings, mechanical action, and the use of detergents. This combination not only ensures effective cleaning but also significantly reduces water and energy consumption compared to manual dishwashing. Detergents play a crucial role in both industrial and domestic cleaning and disinfection processes. The extensive use of these products has substantial economic implications. However, the widespread disposal of detergents leads to environmental concerns. These substances are often non-biodegradable and toxic to living organisms, causing disruptions in biological processes. Enzymes are considered viable alternatives to enhance detergent performance, reducing environmental impact, and promoting sustainability. Incorporating enzymes such as amylases and proteases into detergents eliminates the need for alkaline and highly oxidizing components, which are replaced by bleach activator systems. The introduction of new ingredients in detergent formulations with different functionalities makes the process of designing this type of formulated products complex, requiring systematic studies to assess their stability and performance efficacy under cleaning dishwashing conditions. This is why the development of mathematical tools capable of integrating the mechanisms involved in the different stages of a washing cycle to find the operating conditions, as well as the composition of the formula that maximize the satisfaction of the customer, it is essential. [ES] El lavado de platos es una tarea diaria realizada por millones de personas, ya sea de manera manual o con la ayuda de electrodomésticos de limpieza. Los lavavajillas automáticos están específicamente diseñados para este propósito y se utilizan tanto en entornos domésticos como comerciales. La eficiencia de los lavavajillas automáticos se atribuye a la distribución de varias etapas en el ciclo de lavado, configuraciones de temperatura apropiadas, acción mecánica y el uso de detergentes. Esta combinación no solo garantiza una limpieza efectiva, sino que también reduce significativamente el consumo de agua y energía en comparación con el lavado manual. Los detergentes juegan un papel crucial en los procesos de limpieza y desinfección de ámbitos industriales y domésticos. El uso extensivo de estos productos tiene importantes implicaciones económicas. Sin embargo, el vertido de aguas procedentes de procesos de lavado con detergentes disueltos conlleva problemas ambientales. Estas sustancias a menudo son no biodegradables y tóxicas para los organismos vivos, causando disrupciones en los procesos biológicos. Las enzimas se consideran alternativas viables para mejorar el rendimiento de los detergentes, reduciendo el impacto ambiental y promoviendo la sostenibilidad. La incorporación de enzimas como amilasas y proteasas en los detergentes elimina la necesidad de componentes alcalinos y altamente oxidantes, que son reemplazados por sistemas activadores de blanqueo. La introducción de nuevos ingredientes en las formulaciones de detergentes con diferentes funcionalidades hace que el proceso de diseño de este tipo de productos formulados sea complejo, requiriendo estudios sistemáticos para evaluar su estabilidad y eficacia bajo condiciones de lavado. Por ello, el desarrollo de herramientas matemáticas capaces de integrar los mecanismos involucrados en las diferentes etapas de un ciclo de lavado para encontrar las condiciones operativas de este, así como la composición de la fórmula que maximice la satisfacción del consumidor, es esencial. Wed, 01 Jan 2025 00:00:00 GMT http://hdl.handle.net/10366/166638 2025-01-01T00:00:00Z http://hdl.handle.net/10366/161054 [EN] CONTEXT: A mismatch between nutrient demand and consumption in livestock and cropping systems makes these sectors responsible for 24.5% of greenhouse gas emissions. In order to reduce the gap between the two industries, approaches focused on integrating livestock and crop management have been presented. Location is a key factor in the sustainable operation of these integrated systems since this variable affects both the economic and environmental dimensions of the design of the farm. OBJECTIVE: In this work, a two-step methodology is proposed to address simultaneously the formulation of the feed, the design of the nutrient recovery process, the location of the facilities, and its size, from economic and environmental points of view. METHODS: First, prescreening is used to discard locations that do not meet a series of environmental constraints. Next, an optimization framework is developed by integrating empirical models that estimate the nutritional needs of the animals, fertilizer consumption, waste production, as well as the effect of selection of locations and the size of the farm on the objective function. The farm is designed to produce the feed on the premises and animal wastes are used to produce fertilizers and biogas, implementing the circular economy. The optimization framework is used to estimate the optimal feed formulation, crop selection, size and location, following a multi-objective approach. RESULTS AND CONCLUSIONS: The methodology is applied to a case study in Spain. Of the 345 agricultural districts considered, 145 are discarded in the prescreening. The optimal number of initial animals is 1000. The results show that the selection of ‘Bureba-Ebro’ and a crop distribution that consumes 12% less nutrients than the economic scenario, results in the reduction of 35% in the environmental impact. In addition, meat production cost is 8.87€/kg (1.6€/kg corresponds to the waste treatment). Nevertheless, it can be reduced down to 1.51€/kg by considering the income from crop sales. SIGNIFICANCE: Only through this integrated framework it is possible to determine the feed formulation and facility location that best balance the economic and environmental objective, and determines the percentage of nutrients that can be recovered. The methodology is generic enough to be applied to other locations, crops, and animals. Sat, 01 Jan 2022 00:00:00 GMT http://hdl.handle.net/10366/161054 2022-01-01T00:00:00Z http://hdl.handle.net/10366/161049 [EN] Landfill leachate has an important fraction of humic substances, mainly humic acids (HAs), which often represent more than half value of COD, specially in liquids proceeded from composting processes of organic fraction of solid wastes. We propose in this article a new method of pH sensitive flocculation for COD and colour reduction in landfill leachate based on the chemical properties of HAs. Landfill leachate with a high content of humic acids can be efficiently treated by pH sensitive flocculation at pH 2.0, reducing COD value in 86.1% and colour in 84.7%. Mechanism of pH sensitive flocculation is based in protonation first of phenolic groups and later of carboxylic acid groups in the HAs molecules, resulting in a reduction of Zeta potential value. For pH over neutrality, carboxylic acid and phenolic groups are ionized and Zeta potential increases in absolute value, maintaining HAs in suspension as colloids and conducting flocculation to be obstructed. Ionized anionic groups (carboxylates) can interact electrostatically with cations abundant in leachate (site binding) aiding to maintain HAs in suspension. Simulation of this situation and ideal visualization of Zeta potential behavior is described in the paper and aggregation of molecules by H-bonds is proposed as the main step in separation of HAs from leachate and reduction of COD value in this complex liquid. CHNS analysis, FT-IR spectrometry and UV–VIS spectrophotometry show chemical elements content in the range of natural and commercial HAs, clear aromaticity and carboxylic acids and phenolic groups presence in the precipitate from landfill leachate. Sat, 01 Jan 2022 00:00:00 GMT http://hdl.handle.net/10366/161049 2022-01-01T00:00:00Z http://hdl.handle.net/10366/160870 [EN] The increasing demand of power and the need to reduce our dependency on fossil resources represent an opportunity to valorise low-to-medium grade heat streams such as mild hot streams from industry and natural brines into electricity. A systematic approach is required for the simultaneous selection of thermodynamic cycle which includes its configuration, the thermal fluid, and the optimal operating conditions. A methodology that integrates heuristics, for pre-screening, machine learning, to include rigorous thermodynamics, and mathematical optimization, for process flowsheet design is proposed. The pre-screening yields three fluids, benzene, toluene and 1,1,1,2,3,3,3-heptafluoropropane (R227ea) and two promising cycles, dual pressure organic Rankine cycle (ORC) and organic flash Rankine cycle (OFRC). The mathematical optimization shows that for temperatures over 120 °C, the OFRC using Benzene is the configuration of choice in terms of thermodynamic performance, but the ORC provides the most economical electricity. For hot resources below 120 °C, the efficiency of both cycles converges, but the best fluid turns out to be R227ea alongside the dual ORC cycle showing better performance and lower cost. The cooling costs present a minimum at ΔTmin equal to 8 °C. The results on process design are used to evaluate a exploitation of geothermal resources across Spain. Sat, 01 Jan 2022 00:00:00 GMT http://hdl.handle.net/10366/160870 2022-01-01T00:00:00Z http://hdl.handle.net/10366/159985 [EN] Magnetic sorption process is applied to real wastewater effluents from a Wastewater Treatment Plant. The complex media sorption is done by using different types of magnetic particles (resin and polymeric covered magnetite) giving good results for removing detergents, phosphates and COD and moderate results for the sorption of nitrogen and several heavy metals. Important kinetic parameters were obtained by data fitting for the pseudo first and second order, and for simplified Elovich models. Regeneration and reuse of the magnetic particles using a chemical-free method was also tested, as well as the effect of the concentration of the particles in the removal efficiency (which proved to be relevant). Tue, 02 Mar 2021 00:00:00 GMT http://hdl.handle.net/10366/159985 2021-03-02T00:00:00Z