Examinando por Autor "Morales, Victoria"

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Biocrude from Nannochloropsis gaditana by Hydrothermal Liquefaction: An Experimental Design Approach
(MDPI, 2021-05-11) Sanchez Bayo, Alejandra; Mejia Hervas, Irene; Rodriguez, Rosalía; Morales, Victoria; Vicente, Gemma; Bautista, Luis Fernando
The aim of the present work was focused on optimising the yield and quality of the biocrude obtained by hydrothermal liquefaction (HTL) of Nannochloropsis gaditana. Temperature, reaction time and microalga concentration were the variables used to carry out an experimental factorial design with a central composite design. The responses chosen were the biocrude yield and the nitrogen and oxygen content in the biocrude phase. A second-order model was obtained to predict the responses as a function of these variables. Temperature is the most determining factor with a positive influence on biocrude yield. The maximum biocrude yield (42.3 ± 0.8 wt%) was obtained at 320 ◦C, 10 min of reaction and 10 wt% microalgae concentration, and the nitrogen and oxygen content significantly decreased with respect to their corresponding levels in the initial microalgal biomass. The HHV value of the biocrude was 35.7 MJ/kg. The biocrude was composed of 30% of linear and branched hydrocarbons.
Biodiesel and biogas production from Isochrysis galbana using dry and wet lipid extraction: A biorefinery approach
(Elsevier, 2020) Sánchez-Bayo, Alejandra; López-Chicharro, Daniel; Morales, Victoria; Espada, Juan José; Puyol, Daniel; Martínez, Fernando; Astals, Sergi; Vicente, Gemma; Bautista, Luis Fernando; Rodríguez, Rosalía
Wet lipid extraction combined with residual biomass anaerobic digestion are alternatives to reduce the overall energy consumption of biodiesel production from microalgae. Solvents with different polarities have been studied to assess dry and wet lipid extraction process from Isochrysis galbana microalga. Ethyl acetate (EA) and a chloroform:methanol (CM) mixture yielded the best lipid extraction results in the dry and wet route with suitable lipid compositions. Fatty acid methyl esters (FAMEs) conversion of dry and wet extracted lipids with these solvents was performed by using both homogeneous (H2SO4) and heterogeneous (resin CT 269) catalysts. FAME production from wet extracted lipids with the EA solvent using the CT-269 resin constitutes an advantageous process because it avoids the water elimination step, and the CT-269 is a heterogeneous commercial catalyst, readily to separate after reaction. Lipid-spent microalga was anaerobically digested, obtaining that waste biomass from the wet extraction with EA had the highest methane yield (310 mL CH4/g volatile solids (VS). Energy balance analysis for FAMEs production with EA solvent (wet route) and heterogeneous catalyst yielded an energy recovery of about 80% in terms of biodiesel and biogas. Therefore, this process constitutes a promising route under an energy-driven microalga biorefinery.
Biodiesel Production (FAEEs) by Heterogeneous Combi-Lipase Biocatalysts Using Wet Extracted Lipids from Microalgae
(MDPI, 2019) Sánchez-Bayo, Alejandra; Morales, Victoria; Rodríguez, Rosalía; Vicente, Gemma; Bautista, Luis Fernando
The production of fatty acids ethyl esters (FAEEs) to be used as biodiesel from oleaginous microalgae shows great opportunities as an attractive source for the production of renewable fuels without competing with human food. To ensure the economic viability and environmental sustainability of the microbial biomass as a raw material, the integration of its production and transformation into the biorefinery concept is required. In the present work, lipids from wet Isochrysis galbana microalga were extracted with ethyl acetate with and without drying the microalgal biomass (dry and wet extraction method, respectively). Then, FAEEs were produced by lipase-catalyzed transesterification and esterification of the extracted lipids with ethanol using lipase B from Candida antarctica (CALB) and Pseudomonas cepacia (PC) lipase supported on SBA-15 mesoporous silica functionalized with amino groups. The conversion to FAEEs with CALB (97 and 85.5 mol% for dry and wet extraction, respectively) and PC (91 and 87 mol%) biocatalysts reached higher values than those obtained with commercial Novozym 435 (75 and 69.5 mol%). Due to the heterogeneous nature of the composition of microalgae lipids, mixtures with different CALB:PC biocatalyst ratio were used to improve conversion of wet-extracted lipids. The results showed that a 25:75 combi-lipase produced a significantly higher conversion to FAEEs (97.2 mol%) than those produced by each biocatalyst independently from wet-extracted lipids and similar ones than those obtained by each lipase from the dry extraction method. Therefore, that optimized combi-lipase biocatalyst, along with achieving the highest conversion to FAEEs, would allow improving viability of a biorefinery since biodiesel production could be performed without the energy-intensive step of biomass drying.
Cultivation of Microalgae and Cyanobacteria: Effect of Operating Conditions on Growth and Biomass Composition
(MDPI, 2020) Sánchez-Bayo, Alejandra; Morales, Victoria; Rodríguez, Rosalía; Vicente, Gemma; Bautista, Luis Fernando
The purpose of this work is to define optimal growth conditions to maximise biomass for batch culture of the cyanobacterium Arthrospira maxima and the microalgae Chlorella vulgaris, Isochrysis galbana and Nannochloropsis gaditana. Thus, we study the effect of three variables on cell growth: i.e., inoculum:culture medium volume ratio (5:45, 10:40, 15:35 and 20:30 mL:mL), light:dark photoperiod (8:16, 12:12 and 16:8 h) and type of culture medium, including both synthetic media (Guillard’s F/2 and Walne’s) and wastewaters. The results showed that the initial inoculum:culture medium volume ratio, within the range 5:45 to 20:30, did not affect the amount of biomass at the end of the growth (14 days), whereas high (18 h) or low (6 h) number of hours of daily light was important for cell growth. The contribution of nutrients from different culture media could increase the growth rate of the different species. A. maxima was favoured in seawater enriched with Guillard’s F/2 as well as C. vulgaris and N. gaditana, but in freshwater medium. I. galbana had the greatest growth in the marine environment enriched with Walne’s media. Nitrogen was the limiting nutrient for growth at the end of the exponential phase of growth for C. vulgaris and N. gaditana, while iron was for A. maxima and I. galbana. The growth in different synthetic culture media also determines the biochemical composition of each of the microalgae. All species demonstrated their capability to grow in effluents from a wastewater treatment plant and they efficiently consume nitrogen, especially the three microalga species.
Cytostatic and Cytotoxic Effects of Hollow-Shell Mesoporous Silica Nanoparticles Containing Magnetic Iron Oxide
(MDPI, 2021-09-21) Pérez Garnes, Manuel; Morales, Victoria; Sanz, Raúl; García-Muñoz, Rafael A.
Among the different types of nanoparticles used in biomedical applications, Fe nanoparticles and mesoporous siliceous materials have been extensively investigated because of their possible theranostic applications. Here, we present hollow-shell mesoporous silica nanoparticles that encapsulate iron oxide and that are prepared using a drug-structure-directing agent concept (DSDA), composed of the model drug tryptophan modified by carbon aliphatic hydrocarbon chains. The modified tryptophan can behave as an organic template that allows directing the hollow-shell mesoporous silica framework, as a result of its micellisation and subsequent assembly of the silica around it. The one-pot synthesis procedure facilitates the incorporation of hydrophobically stabilised iron oxide nanoparticles into the hollow internal silica cavities, with the model drug tryptophan in the shell pores, thus enabling the incorporation of different functionalities into the all-in-one nanoparticles named mesoporous silica nanoparticles containing magnetic iron oxide (Fe3O4@MSNs). Additionally, the drug loading capability and the release of tryptophan from the silica nanoparticles were examined, as well as the cytostaticity and cytotoxicity of the Fe3O4@MSNs in different colon cancer cell lines. The results indicate that Fe3O4@MSNs have great potential for drug loading and drug delivery into specific target cells, thereby overcoming the limitations associated with conventional drug formulations, which are unable to selectively reach the sites of interest.
Designing nanocarriers to overcome the limitations in conventional drug administration for Parkinson’s disease
(Medknow Publications, 2022-08) García-Muñoz, Rafael A.; McConnell, Joseph; Morales, Victoria; Sanz, Raúl
Neurodegenerative diseases (NDs) have become one of the leading causes of death and disability worldwide, and cause enormous pain and suffering for both patients and their families. Some of the most common NDs include Alzheimer’s disease, Parkinson’s disease (PD) and Huntington’s disease, among others (Feng, 2020). PD is a widespread neurodegenerative disease that affects more than 10 million people worldwide (No author listed, 2021). The direct cause of the disease is unknown, but it is characterized by the selective degeneration of dopaminergic neurons in the midbrain in the substantia nigra. This leads to the depletion of dopamine (3,4-dihydroxyphenethylamine, DA) in the striatum of patients, in addition to the existence of abnormal α-synuclein in nerve cells and the development of toxic protein aggregates in neurons called Lewy bodies, which causes muscle stiffness, slowness of movements and tremors. It is believed that a combination of genetic and environmental factors may be the cause of PD, but the exact reason for the disease is not yet fully understood. In the treatment of neurological diseases, particularly in PD, NPs can play a remarkable role mainly due to their distinctive thermal, magnetic, and physicochemical properties, such as shape, small size, large specific surface area, hydrophobicity, high loading capacity of different moieties and drugs, chemistry and surface charge, and coating and easy functionalization. The latter allows modifying the NPs surface area with various functional molecules, and therefore introducing the capability that NPs reach target sites by means of active targeting strategies for enhanced uptake in specific cells. Therefore, NPs can help DA or alternative therapies to ensure that they: are not metabolized with uncontrolled effects, do not interfere with other organ function, have lasting effects as a consequence of the slow release in a continuous and sustained way, and are even able to cross the BBB to reach the target sites and escape the reticuloendothelial system, thus reducing drug administration and, therefore, reducing side effects (both adverse and otherwise).
Direct synthesis and post-oxidation of SBA-15 and MCM-41 functionalized with butenyl groups.
(ELSEVIER, 2005) García-Muñoz, Rafael A.; van Grieken, R.; Iglesias, J.; Morales, Victoria ; Martin, J.
Olefins and derivatives are interesting compounds to anchor onto the surface of silica supports since their reactivity allow to form a large variety of organic functionalities. In this work, the synthesis of mesostructured silicas (MCM 41 and SBA 15 type materials) functionalized with butenyl groups is studied through the use of post synthetic grafting or direct synthesis procedures. Results confirm the higher functionalization degree achieved in the final mesostructured materials when using direct synthesis procedures. Unlike MCM 41 materials, which become microporous when high organic content are attached on, SBA 15 type butenyl functionalized silicas keep the features of a mesoporous solid. Post synthetic and in-situ oxidations of butenyl groups during the preparation of the mesostructured silicas have been carried out using H2O2 as oxidant, leading to materials functionalized with glycol species attached to inorganic mesoporous materials, which are attractive to be used as supports for anchoring different catalytic species.
Effect of the dual incorporation of fullerene and polyethyleneimine moieties into SBA-15 materials as platforms for drug delivery
(Springer Nature, 2019-05-28) Martín, A.; Morales, Victoria ; Ortiz-Bustos, J.; Sanz, R.; García-Muñoz, Rafael A.
Mesostructured SBA-15 silica materials have been successfully dual functionalized with polyethyleneimine (PEI) groups and C60 fullerene moieties to allow an evaluation of their properties as nanovehicles for controlled drug delivery. Methylprednisolone sodium succinate was selected as a model drug for adsorption on the surface of functionalized SBA-15 silica materials. The resulting dual-functionalized SBA-15 silica materials exhibit mesoscopic arrangements, although with a remarkable reduction in their textural properties as compared to pure silica SBA-15. The adsorption capacity of methylprednisolone on functionalized SBA-15-PEI improved remarkably compared with that of raw SBA-15, while the drug release rate slowed, as the amount of PEI anchored in the SBA-15 increased. The strong attractive electrostatic interactions between methylprednisolone and the silica surfaces of SBA-15-PEI materials, measured by zeta potential, account for these results. In a second step, wherein C60 fullerene species in combination with PEI were grafted to the silica, the results establish that the steric effects and hydrophobicity of the C60 moieties hinder methylprednisolone transport within the silica pores. The kinetic parameters obtained from the drug release profiles, fitted to four kinetic models, show that the incorporation of C60 species yields lower methylprednisolone release rates from SBA-15-PEI-C60 materials than from SBA-15-PEI materials. Additionally, the incorporation of fullerene groups into PEI-modified materials provides an increment in cell viability. Confocal microscopy evidences the cellular internalization of the dual-functionalized mesoporous SBA-15 materials inside the plasmatic membrane.
Engineering hollow mesoporous silica nanoparticles to increase cytotoxicity
(2020-07) Perez-Garnes, M; Gutiérrez-Salmerón, M; Morales, Victoria ; Chocarro-Calvo, A; Sanz, R; García-Jiménez, C; García-Muñoz, Rafael A.
Hollow mesoporous silica nanoparticles (HMSNs) consist of a network of cavities confined by mesoporous shells that have emerged as promising tools for drug delivery or diagnostic. The physicochemical properties of HMSNs are dictated by the synthesis conditions but which conditions affect which property and how it impacts on biological interactions is unclear. Here by changing the concentration of the structure-directing agent (SDA), the pH and the ratio between SDA and added salt (NaCl) we determine the effects in size, morphology, surface charge and density or degree of compaction (physicochemical properties) of HMSNs and define their impact on their biological interactions with human colon cancer or healthy cells at the level of cellular uptake and viability. Increased size or density/degree of compaction of HMSNs increases their cytotoxicity. Strikingly, high salt concentrations in the synthesis medium leads to a spiky-shell morphology that provokes nuclear fragmentation and irreversible cell damage turning HMSNs lethal and unveiling intrinsic therapeutic potential. This strategy may open new avenues to design HMSNs nanoarchitectures with intrinsic therapeutic properties without incorporation of external pharmaceutical ingredients.
Environmental analysis of Spirulina cultivation and biogas production using experimental and simulation approach
(Elsevier, 2018-12) Rodríguez, Rosalía; Espada, Juan José; Moreno, Jovita; Vicente, Gemma; Bautista, Luis Fernando; Morales, Victoria
Microalgae is constituted by different compounds, interesting for the production of a wide range of endproducts by using different technologies. Many potential possibilities have been developed under the context of a biorefinery. The aim of this work is to evaluate the environmental performance of biogas production from Spirulina (Arthrospira maxima) through LCA using experimental and simulation results. For this purpose, kinetic models for batch cultivation and anaerobic digestion (AD) were determined from experimental data. Thus, Monod kinetic model and a first order model describe well microalgal biomass growth and AD, respectively. This model was used to simulate growth of Spirulina in a continuous system by using SuperPro Designer 9.5. Calculated results were compared to continuous experimental ones, obtaining good agreement in all cases. On the other hand, the whole process (cultivation, dewatering and AD of Spirulina biomass) was also simulated and the obtained results (material and energy balances) were used to construct LCA inventory data. Thereafter, environmental impacts were quantified through CML-2001 methodology using software Gabi 6.0. LCA results show that abiotic depletion of fossil resources (ADFR) category presents the highest impact, being biomass cultivation the most important contributor (about 56%). This result is directly related to the high energy consumption required for nutrient production, which also leads to increase remarkably the global warming potential (GWP) category. Main conclusion of the work is that the total/partial substitution of mineral fertilizers as nutrient source is the key to improve the environmental performance of the studied process. In this sense, a potential alternative could be the use of nutrients from wastewater or other wast
Functionalization of SBA-15 by an Acid-Catalyzed Approach. A Surface Characterization Study
(ELSEVIER, 2007) García, Nuria; Benito, Esperanza; Guzmán, Julio; Tiemblo, Pilar; Morales, Victoria; García-Muñoz, Rafael A.
The functionalization of a mesoporous ordered silica, SBA-15, by a grafting strategy has been successfully achieved. The derivatized SBA-15 products with trimethylmethoxy silane, vinyltrimethoxy silane and octyltrimethoxy silane have been characterized by BET analysis, DRX analysis, thermogravimetric analysis and NMR techniques. The use of p-toluenesulfonic acid as catalyst and the azeotropic distillation of the alcohol generated in the hydrolysis and condensation of the silanes allowed the incorporation of high amounts of organic loading in shorter times as compared to conventional toluene reflux method. The surface of the resulting materials has been thoroughly analyzed and the concentration of total and residual silanols and silane molecules attached on the surface has been quantitatively determined. Being the as-modified SBA-15 materials hydrophobic as a rule, the accessibility of the residual silanol population, evaluated by a deuterium exchange method and subsequent cross polarization NMR analysis, depends on the nature of the surface organic layer.
Hydrothermal Liquefaction of Microalga Using Metal Oxide Catalyst
(MDPI, 2020) Sánchez-Bayo, Alejandra; Rodríguez, Rosalía; Morales, Victoria; Nasirian, Nima; Bautista, Luis Fernando; Vicente, Gemma
The yield and composition of the biocrude obtained by hydrothermal liquefaction (HTL) of Nannocloropsis gaditana using heterogeneous catalysts were evaluated. The catalysts were based on metal oxides (CaO, CeO2, La2O3, MnO2, and Al2O3). The reactions were performed in a batch autoclave reactor at 320 C for 10 min with a 1:10 (wt/wt) microalga:water ratio. These catalysts increased the yield of the liquefaction phase (from 94.14 wt% for La2O3 to 99.49 wt% for MnO2) as compared with the thermal reaction (92.60 wt%). Consequently, the biocrude yields also raised in the metal oxides catalysed HTL, showing values remarkably higher for the CaO (49.73 wt%) in comparison to the HTL without catalyst (42.60 wt%). The N and O content of the biocrude obtained from non-catalytic HTL were 6.11 wt% and 10.50 wt%, respectively. In this sense, the use of the metal oxides decreased the N content of the biocrude (4.62–5.45 wt%), although, they kept constant or increased its O content (11.39 –21.68 wt%). This study shows that CaO, CeO2 and Al2O3 can be promising catalysts based on the remarkable amount of biocrude, the highest values of C, H, heating value, energy recovery, and the lowest content of N, O and S.
Kidney-Protector Lipidic Cilastatin Derivatives as Structure-Directing Agents for the Synthesis of Mesoporous Silica Nanoparticles for Drug Delivery
(MDPI (Multidisciplinary Digital Publishing Institute), 2021-07-26) Martínez Erro, Samuel; Navas, Francisco; Romaní Cubells, Eva; Fernández García, Paloma; Morales, Victoria; Sanz, Raúl; García-Muñoz, Rafael A.
Mesoporous silica nanomaterials have emerged as promising vehicles in controlled drug delivery systems due to their ability to selectively transport, protect, and release pharmaceuticals in a controlled and sustained manner. One drawback of these drug delivery systems is their preparation procedure that usually requires several steps including the removal of the structure-directing agent (surfactant) and the later loading of the drug into the porous structure. Herein, we describe the preparation of mesoporous silica nanoparticles, as drug delivery systems from structure-directing agents based on the kidney-protector drug cilastatin in a simple, fast, and one-step process. The concept of drug-structure-directing agent (DSDA) allows the use of lipidic derivatives of cilastatin to direct the successful formation of mesoporous silica nanoparticles (MSNs). The inherent pharmacological activity of the surfactant DSDA cilastatin-based template permits that the MSNs can be directly employed as drug delivery nanocarriers, without the need of extra steps. MSNs thus synthesized have shown good sphericity and remarkable textural properties. The size of the nanoparticles can be adjusted by simply selecting the stirring speed, time, and aging temperature during the synthesis procedure. Moreover, the release experiments performed on these materials afforded a slow and sustained drug release over several days, which illustrates the MSNs potential utility as drug delivery system for the cilastatin cargo kidney protector. While most nanotechnology strategies focused on combating the different illnesses this methodology emphasizes on reducing the kidney toxicity associated to cancer chemotherapy.
L‑arginine‑containing mesoporous silica nanoparticles embedded in dental adhesive (Arg@MSN@DAdh) for targeting cariogenic bacteria
(BioMed Central, 2022-12-01) López Ruíz, Marta; Navas, Francisco; Fernández García, Paloma; Martínez Erro, Samuel; Fuentes, María Victoria; Giráldez, isabeI; Ceballos, Laura; Ferrer Luque, Carmen María; Ruíz Linares, Matilde; Morales, Victoria; Sanz, Raúl; García-Muñoz, Rafael A.
Dental caries is the major biofilm-mediated oral disease in the world. The main treatment to restore caries lesions consists of the use of adhesive resin composites due to their good properties. However, the progressive degradation of the adhesive in the medium term makes possible the proliferation of cariogenic bacteria allowing secondary caries to emerge. In this study, a dental adhesive incorporating a drug delivery system based on L-arginine-containing mesoporous silica nanoparticles (MSNs) was used to release this essential amino acid as a source of basicity to neutralize the harmful acidic conditions that mediate the development of dental secondary caries. The in vitro and bacterial culture experiments proved that L-arginine was released in a sustained way from MSNs and diffused out from the dental adhesive, effectively contributing to the reduction of the bacterial strains Streptococcus mutans and Lactobacillus casei. Furthermore, the mechanical and bonding properties of the dental adhesive did not change significantly after the incorporation of L-arginine-containing MSNs. These results are yielding glimmers of promise for the costeffective prevention of secondary caries.
L-Dopa release from mesoporous silica nanoparticles engineered through the concept of drug-structure-directing agents for Parkinson’s disease
(Royal Society of Chemistry, 2021-04-26) Morales, Victoria; McConnell, Joseph; Pérez-Garnes, Manuel; Almendro, Nuria; Sanz, Raúl; García-Muñoz, Rafael A.
Parkinson’s disease (PD) is a progressive neurodegenerative disease, the 2nd most common after Alzheimer’s disease, the main effect of which is the loss of dopaminergic neurons. Levodopa or L-Dopa is an amino acid used in the treatment of PD that acts as the immediate precursor to dopamine. However, over time the efficacy of the medication gradually decreases requiring modified delivery methods. One of the major challenges for the medication to work is to achieve a gradual continuous supply of L-Dopa to the brain to minimise symptoms. Herein, mesoporous silica nanoparticles (MSNs) were engineered through the concept of drug-structure-directing agents (DSDAs) with inherent therapeutic activity. The DSDA used was L-Dopa drug modified by amidation with fatty acids to buildanionic surfactants that were able to form micelles as templates for the assembly of inorganic precursors to form the silica framework. This templating route produced MSNs with tunable sizes ranging from 100 nm to 1 mm and with different shapes: spherical, with either solid structures with radial mesopores and porous shells, or hollow-shells with inside large void cavities; and elongated, characterized by long hollows covered by mesoporous shells. The concept of using DSDAs to synthesize drug nanocarriers can be used to avoid the surfactant removal and subsequent drug loading steps involved in the synthesis of conventional MSNs. We hypothesized that the L-Dopa released from MSN materials is mediated by the size and solubility of the DSDAs, and the surface chemical interactions between the DSDAs and MSN hosts. Different pHs (acidic and neutral) simulating gastrointestinal tract conditions were tested, and the results showed hardly any release for gastric conditions at pH 1.2, avoiding the premature release in the stomach typical of conventional MSNs, while for intestinal conditions of pH 7.4, the release of L-Dopa occurred in a continuous and sustained manner, which is well suited to the drug’s application and delivery route, and matches well with achieving a sustained L-Dopa delivery to relief symptoms. This could open up new uses for MSNs synthesized by this approach to treat PD.
Magnetically modified-mitoxantrone mesoporous organosilica drugs: an emergent multimodal nanochemotherapy for breast cancer
(Springer Nature, 2024-04-14) Romaní Cubells , Eva; Martínez Erro, Samuel; Morales, Victoria; Chocarro Calvo, Ana; García Martinez, Jose M.; Sanz, Raúl; García Jimenez, Custodia; García-Muñoz, Rafael A.
Background Chemotherapy, the mainstay treatment for metastatic cancer, presents serious side effects due to off-target exposure. In addition to the negative impact on patients’ quality of life, side effects limit the dose that can be administered and thus the efficacy of the drug. Encapsulation of chemotherapeutic drugs in nanocarriers is a promising strategy to mitigate these issues. However, avoiding premature drug release from the nanocarriers and selectively targeting the tumour remains a challenge. Results In this study, we present a pioneering method for drug integration into nanoparticles known as mesoporous organosilica drugs (MODs), a distinctive variant of periodic mesoporous organosilica nanoparticles (PMOs) in which the drug is an inherent component of the silica nanoparticle structure. This groundbreaking approach involves the chemical modification of drugs to produce bis-organosilane prodrugs, which act as silica precursors for MOD synthesis. Mitoxantrone (MTO), a drug used to treat metastatic breast cancer, was selected for the development of MTO@MOD nanomedicines, which demonstrated a significant reduction in breast cancer cell viability. Several MODs with different amounts of MTO were synthesised and found to be efficient nanoplatforms for the sustained delivery of MTO after biodegradation. In addition, Fe3O4 NPs were incorporated into the MODs to generate magnetic MODs to actively target the tumour and further enhance drug efficacy. Importantly, magnetic MTO@MODs underwent a Fenton reaction, which increased cancer cell death twofold compared to non-magnetic MODs. Conclusions A new PMO-based material, MOD nanomedicines, was synthesised using the chemotherapeutic drug MTO as a silica precursor. MTO@MOD nanomedicines demonstrated their efficacy in significantly reducing the viability of breast cancer cells. In addition, we incorporated Fe3O4 into MODs to generate magnetic MODs for active tumour targeting and enhanced drug efficacy by ROS generation. These findings pave the way for the designing of silica-based multitherapeutic nanomedicines for cancer treatment with improved drug delivery, reduced side effects and enhanced efficacy.
Mild Hydrothermal Pretreatment of Microalgae for the Production of Biocrude with a Low N and O Content
(MDPI, 2019-09-17) Montero-Hidalgo, Miriam; Espada, Juan Jose; Rodriguez, Rosalía; Morales, Victoria; Bautista, Luis Fernando; Vicente, Gemma
A hydrothermal pretreatment of the microalga Nannochloropsis gaditana at mild temperatures was studied in order to reduce the N and O content in the biocrude obtained by hydrothermal liquefaction (HTL). The work focused on the evaluation of temperature, reactor loading, and time (factors) to maximize the yield of the pretreated biomass and the heteroatom contents transferred from the microalga biomass to the aqueous phase (responses). The study followed the factorial design and response surface methodology. An equation for every response was obtained, which led to the accurate calculation of the operating conditions required to obtain a given value of these responses. Temperature and time are critical factors with a negative effect on the pretreated biomass yield but a positive one on the N and O recovery in the aqueous phase. The slurry concentration has to be low to increase heteroatom recovery and has to be high to maximize the pretreated microalga yields. Response equations were obtained for the analyzed responses, which facilitated the accurate prediction of the operating conditions required to obtain a given value of these responses.
Mitoxantrone-Derivative Drug Structure-Directing Agent for the Synthesis of Magnetic Mesoporous Silica Nanoparticles for Breast Cancer Treatment
(American Chemical Society, 2024-05-20) Romaní-Cubells, Eva; Martinez-Erro, Samuel; Morales, Victoria; Grieken, Rafael van; García-Muñoz, Rafael A.; Sanz, Raúl
Cancer causes hundreds of thousands of deaths worldwide each year. Chemotherapy, the treatment of choice for invasive cancers, presents severe side effects related to off-target exposure that limit its dosage and, thus, its efficacy. Nanomedicine has emerged as a potential tool to overcome these problems. Among the nanocarriers, mesoporous silica nanoparticles (MSNs) have attracted much attention due to their high surface area (up to 1000 m2 g–1), the versatility in size and pore diameter, and their ease of functionalization. However, drug leakage from the MSNs usually occurs before the nanocarriers reach their target, reducing drug efficacy and causing adverse effects. Our group has developed a promising method to increase drug loading capacity while preventing premature drug release. This strategy consists of the use of a drug structure-directing agent (DSDA) that plays a dual role, acting as a pharmacological prodrug and as a template for the synthesis of MSNs. Here, we successfully synthesized a DSDA from the anticancer drug mitoxantrone (MTO), which is used in clinical practice for the treatment of metastatic breast cancer, and used it to synthesize magnetic MSNs whose porosity was fully filled with the MTO prodrug (magnetic MTO-C12@MSNs). The release behavior was pH-dependent, showing negligible drug release at physiological pH and a significant increase at the pH of the tumoral microenvironment. Finally, the efficacy of magnetic MTO-C12@MSNs in reducing breast cancer cell viability was confirmed, demonstrating the potential of this material as an efficient drug delivery system to target breast cancer tumors while avoiding side effects.
Modelling the adsorption and controlled release of drugs from the pure and amino surface-functionalized mesoporous silica hosts
(Elsevier, 2018-05-15) Martín, A.; Morales, Victoria ; Ortiz-Bustos, J.; Pérez-Garnés, M.; Bautista, L.F.; García-Muñoz, Rafael A.
Several mesoporous silica materials with different structures were investigated as matrices for controlled drug delivery. The aim of this study is correlating the textural and surface chemical properties of these materials with the adsorption and delivery of the drug model methylprednisolone sodium succinate. The materials were synthesized according to different protocols, and employing both cationic and non-ionic surfactants. Additionally, the functionalization of the materials' surface with 1-[3-(trimethoxysilyl)propyl]diethylenetriamine (DT) was accomplished to study the synergistic effect of the incorporation of amine groups and textural properties on the loading and delivery of drug. The thermodynamics and dynamic adsorption behavior of these materials were determined and fitted to several isotherms models to provide information about the drug adsorption processes. The maximum adsorption capacities of the raw silica supports were correlated with the pore size and the results indicated that the drug adsorption ability improved as the material pore size increases. Moreover, it is observed that the drug adsorption on materials with mesoporous size higher than 10 nm are very close to the theoretical saturation capacity. Regarding amino-modified materials, isotherms models confirmed that the factor governing the adsorption process were mainly the electrostatic interactions, hydrogen bonding and/or hydrophobic-hydrophilic interactions between the drug moieties and amino-functionalized silica surfaces, and in a lesser degree the textural properties of the support. Furthermore, the kinetics of the drug release from these materials functionalized with amino groups were also modelled to finally obtain a correlation between the adsorption and release drug cargo from the host pure and surface-functionalized materials.
New Drug-Structure-Directing Agent Concept: Inherent Pharmacological Activity Combined with Templating Solid and Hollow-Shell Mesostructured Silica Nanoparticles
(2016-10-25) Morales, Victoria; Gutiérrez-Salmerón, María; Balabasquer, M; Ortiz, J; Linder, C; Chocarro-Calvo, Ana; García-Jiménez, Custodia; García-Muñoz, Rafael A.
One of the major challenges in medicine is the delivery and control of drug release over time. Current approaches take advantage of mesostructured silica nanoparticles (MSNs) as carriers but suffer several problems including complex synthesis that requires sequential steps for (1) removal of surfactants and (2) functionalization of MSNs to allow upload of the drugs. Here, a novel solution is presented to these restrictions: the design of drug-structure-directing agents (DSDAs) with dual inherent pharmacological activity and ability to direct the formation of solid and hollow-shell MSNs. Pharmacologically active DSDAs obtained by amidation of drugs with fatty acids are allowed to form micelles, around which the inorganic species self-assembled to form MSNs. Since the DSDAs direct the formation of MSNs, the steps to remove surfactants, functionalization, and drug upload are not required. The MSNs thus prepared provide sustained release of the drug over more than six months, as well as rapid cellular internalization by both physiological and tumoral human colon cells without affecting cell viability. Moreover, the gradual intracellular release of both, the active drug and lipid moiety with potential nutraceutical properties is proved. MSN particles designed with this approach are promising vehicles for controlled and sustained intra-or extracellular drug-delivery.