http://hdl.handle.net/10366/4378 2026-05-02T06:56:01Z 2026-05-02T06:56:01Z Nieto Jiménez, Celia Vega Moreno, Milena Amparo Enrique, Jesús Marcelo, Gema Martín del Valle, Eva María http://hdl.handle.net/10366/170168 2026-02-28T01:02:47Z 2019-10-29T00:00:00Z

[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.

2019-10-29T00:00:00Z Nieto Jiménez, Celia Vega Moreno, Milena Amparo Marcelo, Gema Martín del Valle, Eva María http://hdl.handle.net/10366/169278 2026-01-27T01:01:21Z 2018-10-08T00:00:00Z

[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.

2018-10-08T00:00:00Z Vega Moreno, Milena Amparo Nieto Jiménez, Celia Marcelo, Gema Martín del Valle, Eva María http://hdl.handle.net/10366/169275 2026-01-27T01:01:18Z 2018-07-01T00:00:00Z

[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.

2018-07-01T00:00:00Z Djermane, Rania Nieto Jiménez, Celia Vargas, Julio Vega Moreno, Milena Amparo Martín del Valle, Eva http://hdl.handle.net/10366/169109 2026-01-22T01:01:32Z 2022-01-01T00:00:00Z

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.

2022-01-01T00:00:00Z Nieto Jiménez, Celia Vega Moreno, Milena Amparo Martín del Valle, Eva María http://hdl.handle.net/10366/169108 2026-01-22T01:01:19Z 2021-01-01T00:00:00Z

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.

2021-01-01T00:00:00Z Alonso, Carlos Nieto Jiménez, Celia Vargas, Julio Vega Moreno, Milena Amparo Martín del Valle, Eva María http://hdl.handle.net/10366/169107 2026-01-22T01:01:17Z 2024-01-01T00:00:00Z

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.

2024-01-01T00:00:00Z Djermane, Rania Nieto Jiménez, Celia Vega Moreno, Milena Amparo Martín del Valle, Eva María http://hdl.handle.net/10366/169106 2026-01-22T01:01:14Z 2024-01-01T00:00:00Z

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.

2024-01-01T00:00:00Z Djermane, Rania http://hdl.handle.net/10366/167070 2025-09-20T02:03:23Z 2025-01-01T00:00:00Z

[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.

2025-01-01T00:00:00Z Blanco López, Marcos Dios Pérez, Inmaculada de González Garcinuño, Álvaro Tabernero de Paz, Antonio Martín del Valle, Eva María http://hdl.handle.net/10366/166865 2025-09-03T00:02:37Z 2025-01-01T00:00:00Z

[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.

2025-01-01T00:00:00Z Blanco López, Marcos Marcos García, Alejandro González Garcinuño, Álvaro Tabernero de Paz, Antonio Martín del Valle, Eva María http://hdl.handle.net/10366/166757 2025-08-01T00:02:27Z 2024-01-01T00:00:00Z

[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.

2024-01-01T00:00:00Z Taifouris, Manuel Martín Martín, Mariano http://hdl.handle.net/10366/161054 2025-04-30T20:18:32Z 2022-01-01T00:00:00Z

[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.

2022-01-01T00:00:00Z Riascos, Brayan D. Quintero, Xavier E. Pinedo, M. Laura Costa Pérez, Carlos http://hdl.handle.net/10366/161049 2025-04-30T20:18:33Z 2022-01-01T00:00:00Z

[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.

2022-01-01T00:00:00Z García-Anteportalatina, Víctor Manuel Martín Martín, Mariano http://hdl.handle.net/10366/160870 2025-04-30T20:18:33Z 2022-01-01T00:00:00Z

[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.

2022-01-01T00:00:00Z Barbosa, Domingos Castelo-Grande, Teresa Augusto, Paulo A. Rico, Javier Marcos, Jorge Iglesias, Roberto Hernández, Lorenzo http://hdl.handle.net/10366/159985 2025-04-30T20:18:33Z 2021-03-02T00:00:00Z

[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).

2021-03-02T00:00:00Z Hernández, Lorenzo Augusto, Paulo A. Castelo-Grande, Teresa Barbosa, Domingos http://hdl.handle.net/10366/159984 2025-04-30T20:18:34Z 2021-02-27T00:00:00Z

[EN] Fenton reaction is an oxidation process of interest in wastewater treatment because of its ability to degrade organic compounds. Iron-based magnetic particles can be a very useful catalyst when using heterogeneous Fenton process. The major problem of this heterogeneous process is the saturation of the Fe 3+ on the surface, which limits the process. In this study, the possibility of using magnetite particles as a substrate is presented, increasing its degradation efficiency by Fenton reaction through a regeneration process that achieves the electronic reduction of its surface using reducing agents. The results indicate that the regeneration process is quite effective, increasing the efficiency of the degradation of Methylene Blue up to 99%. The concentration of magnetite is the most influential factor in the efficiency of the reaction, while the regeneration time and the concentration of reducing agent do not significantly affect the results considering the range used. The presence of mechanical stirring may adversely affect the reaction in the long term. Increasing the oxidant agent concentration reduces the initial speed of the reaction but not the long-term efficiency. The use of hydrazine in this process allows the successive reuse of these particles maintaining a high percentage of elimination of methylene blue, above 70% even after 10 uses, compared to an elimination below 20% for particles not regenerated after the second use and for particles regenerated with ascorbic acid after the eighth use.

2021-02-27T00:00:00Z Martín, Mariano http://hdl.handle.net/10366/159551 2025-04-30T20:18:34Z 2022-01-01T00:00:00Z

[EN] The most abundant energy on Earth is solar and it is a versatile resource that is to be used to improve the sustainability of the chemical and process industry. Two main pillars support these industries, the raw materials and energy. Energy in the chemical industry is to be provided in the form of utilities such as steam, thermal energy and power. All of them can be provided by transforming solar thermal energy. This work presents the perspectives on the process integration of solar thermal plants and/or solar thermal energy within the chemical industry, describing the state of the art and the technology readiness level of units and facilities as well as the challenges and opportunities that the integration of solar thermal energy in the chemical industry generate for the process system engineering community, aiming at reaching the goals of the agenda 2030.

2022-01-01T00:00:00Z