Artículos (Química Orgánica y Farmacéutica)

URI permanente para esta colecciónhttps://hdl.handle.net/11441/11085

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A new biodegradable polythiourethane as controlled release matrix polymer
(Elsevier, 2015-03-01) Campiñez, M. D.; Ferris Villanueva, Cristina; Paz Báñez, María Violante de; Aguilar de Leyva, Mercedes Ángela; Galbis Pérez, Juan Antonio; Caraballo Rodríguez, Isidoro; Química Orgánica y Farmacéutica; Farmacia y Tecnología Farmacéutica; Ministerio de Economía y Competitividad (MINECO). España
The main aim of this paper is the synthesis and characterization of a new linear functional biodegradable polythiourethane-d,l-1,4-dithiothreitol-hexamethylene diisocyanate [PTU(DTT-HMDI)]. The SeDeM diagram has been obtained to investigate its suitability to be processed through a direct compression process. Furthermore, the ability of this polymer to act as controlled release matrix forming excipient has been studied. Four batches of matrices containing 10–40% of polymer and theophylline anhydrous as model drug have been manufactured. Release studies have been carried out using the paddle method and the polymer percolation threshold has been estimated. The principal parameters of the SeDeM Expert system, such as the parametric profile (mean radius) and the good compression index (IGC = 4.59) for the polymer are very close to the values considered as adequate for direct compression even with no addition of flow agents. Furthermore, the results of the drug release studies show a high ability of the polymer to control the drug release. The excipient percolation threshold has been estimated between 20% and 30% w/w of polymer.
Reduction-sensitive functionalized copolyurethanes for biomedical applications
(Royal Society of Chemistry, 2014) Ferris, Cristina; Paz Báñez, María Violante de; Aguilar de Leyva, Mercedes Ángela; Caraballo Rodríguez, Isidoro; Galbis Pérez, Juan Antonio; Química Orgánica y Farmacéutica; Farmacia y Tecnología Farmacéutica; Ministerio de Economía y Competitividad (MINECO). España
In the present paper we combine functionalization and biodegradation in the rational design of polymers that can be used as carrier systems for drug delivery in the colon. Functionalization of new polyurethanes (PUs) was achieved by thiol–ene coupling reactions, a simple and straightforward procedure included among the so-called click reactions, which are currently accepted as one of the most powerful tools in organic chemistry. Enhancement of the degradability of the new materials by the introduction of disulfide linkages into the polymer backbone has led to a new group of stimulusresponsive sugar-based polyurethanes able to be degraded by tripeptide glutathione under physiological conditions. Atomic Force Microscopy (AFM) on solid-supported multilayered dry polymer films— prepared by spin-coating from dimethylsulfoxide solutions—was used to study the morphology of the polymers and the degradation process in reductive environments. Matrix systems containing polymers selected according to their rheological properties were also investigated as modulated methotrexaterelease systems.
Amphiphile-Assisted Synthesis of Ruthenium Nanoparticles for Controlled Release and Enhanced Antibacterial Activity
(Wiley, 2025-11-19) Gimeno Ferrero, Raúl; Estruch Blasco, Manel; Pajuelo Domínguez, Eloísa; Fernández Fernández, Inmaculada; García Martín M. L.; Pernia Leal, Manuel; Microbiología y Parasitología; Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Junta de Andalucía; European Union (UE); Universidad de Sevilla
A novel procedure for preparing Ruthenium nanoparticles (RuNPs) based onlow-molecular-weight amphiphilic molecules and Ru(III) complexes asantibacterial agents with controlled release properties has been developed.Two hydrophobic Ru(III) complexes, Ru-TOA and Ru-Benza, analogs to theNAMI-A prodrug, are encapsulated within the core of the micelles formedthrough the self-assembly of these amphiphiles. The self-assembly ofamphiphile I, which contains a double polar head, results in highlywater-stable and monodispersed RuNPs incorporating both hydrophobic Rucomplexes. These RuNPs exhibit hydrodynamic sizes ranging from 26.7 to104.2 nm for NPs derived from Ru-TOA complex, and ≈10 nm for thosederived from Ru-Benza. Compared to Ru(III) complexes, these RuNPs oﬀerseveral advantages, including protection from aqueous degradation andenhanced bacterial uptake. Moreover, post-synthesis modiﬁcation of theRuNPs with molecular staples based on polyethylene glycol chains of varyinglengths enables controlled Ru release, reducing the burst eﬀect. Interestingly,these RuNPs demonstrate excellent antibacterial activity, with minimuminhibitory concentration (MIC) values of 16 mg·L−1 and minimum bactericidalconcentration (MBC) values of 32 mg·L−1 against a broad range ofGram-positive bacteria, including S. aureus, Staphylococus pseudintermedius,and Enterococcus faecalis, highlighting their potential eﬃcacy againstclinically relevant bacterial strains.
Layer-by-layer electrospun PCL/PVA mats loaded with nisin Z for enhanced diabetic foot ulcer treatment
(Elsevier, 2025-09-30) Tavares, Tânia D.; Pinho, Sonia L.C.; Delgado-Pujol, Ernesto J.; Begines Ruiz, Belén; Alcudia Cruz, Ana; Silva, Carla Carolina; Felgueiras, Helena P.; Química Orgánica y Farmacéutica; European Union (UE); Foundation for Science and Technology of Portugal (FCT); Centre of Biological Engineering (CEB), Portugal; Ministerio de Ciencia, Innovación y Universidades (MICIU). España
Diabetic foot ulcers (DFUs) represent a significant clinical challenge due to impaired healing and high susceptibility to infections, underscoring the urgent need for multifunctional wound dressings. This study explores the potential of multilayered electrospun mats composed of polycaprolactone (PCL) and poly(vinyl alcohol) (PVA) engineered by a layer-by-layer (LbL) electrospun-based deposition, and functionalized with the antimicrobial peptide (AMP) nisin Z. Three LbL configurations (PCL/PVA, PCL/PVA/PCL, and PCL/PVA/PCL/PVA) were produced and characterized in terms of physicochemical, mechanical and biological performance. The mats exhibited tensile strengths of 0.9–2.7 MPa, swelling degree < 90 % and ≈ 20 % degradation after 7 and 28 days under physiological-like environments, respectively, while maintaining air permeability between 0.5 and 1.3 mL/cm2/s. Biocompatibility assays using HaCaT keratinocytes demonstrated excellent cytocompatibility, with metabolic activity exceeding 93 %, cell growth above 87 %, and enhanced cell migration leading to wound closure within 16 h. The incorporation of nisin Z provided significant antimicrobial activity against Gram-positive bacteria, Staphylococcus aureus and Staphylococcus epidermidis, achieving up to 100 % bacterial inhibition within 24 h, and reducing biofilm formation by more than 50 %. Among the tested mats, the PCL/PVA/PCL configuration revealed the most promising features. Overall, these findings highlight the potential of multilayer electrospun mats as bioactive wound dressings for DFUs, offering a multi-action strategy for improved wound healing.
Harnessing coumarin-thio(seleno)cyanate conjugates: potent In vivo antiproliferative agents targeting carbonic anhydrases
(Taylor & Francis, 2025-10-10) Meza Ireta, Silvia Alejandra; Romero Hernández, Laura L.; Begines Aguilar, Paloma; Giouvannuzi, Simone; Puerta, Adrián; Romero Franco, Amador; Huertas Sánchez, Pablo; Fernández-Bolaños Guzmán, José María; Castellano Pozo, Maikel; López López, Óscar; Química Orgánica y Farmacéutica; Genética; Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. España; European Union (UE)
We synthesised coumarin-based derivatives bearing thio- and selenocyanates to selectively inhibit tumour-associated carbonic anhydrases (CAs) IX and XII and to exert antiproliferative effects on tumour cells. Structural variations included chalcogen atom type (S, Se), substitutions at C-3/C-4, and tether length at C-7 of the coumarin core. Thiocyanates 4 and 7b showed potent CA IX/XII inhibition (Ki = 17.9–27.4nM) with >5000-fold selectivity over off-target isoforms (CAs I and II). Selenocyanate 8a exhibited strong antiproliferative activity (GI 50 = 0.78–2.6µM) across six human solid tumour cell lines. Mechanistic studies revealed a cytostatic effect via cell cycle arrest and reduced mitotic progression. In vivo assays in Caenorhabditis elegans confirmed selective cytostatic action of selenocyanate 8c, reducing tumorous germline size without affecting healthy tissues at therapeutic doses.
Polymeric Materials for the Development of Dual-Working Gastroretentive Drug Delivery Systems. A Breakthrough Approach
(Juniper Publishers, 2021-02-04) Paz Báñez, María Violante de; Grosso, Roberto; García Martín, Maria de Gracia; Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Junta de Andalucía
Oral route is the most convenient and widely used method of drug administration, representing about 90% of all therapies used. It displays great advantages, such as being non-invasive, easy to administer (with the consequent high patient compliance) and cost-effective. However, serious drawbacks to conventional oral dosage forms are imposed by the gastrointestinal tract. Large fluctuations in drug bioavailability are found due to the influence of physiological factors such as variations in pH, high enzymatic activity and gastric emptying. This is the reason why frequent drug administrations are required to maintain the therapeutic plasma level of the drug. Gastroretentive Drug Delivery Systems (GRDDS) have emerged as an ideal approach to overcome these drawbacks. They are designed to prolong the gastric residence time (GRT) of the dosage forms in the stomach so that the time between dose administration is lengthened. Although their development has partially overcome the drawbacks associated with conventional dosage form, further work is needed on its shortcomings. The overall objective of this minireview is to highlight the opportunities from the development of dual-working polymeric materials, suitable for their use as GRDDS with improved GRT and capable of overcoming common drawbacks associated with conventional GRDDS. This could be achieved by a combination of properties such as buoyancy, swelling, porosity, and bioadhesion of the synthesized materials.
Stability of thermolabile drugs at room temperature. A review
(Elsevier, 2025-10) Suárez Casillas, Paloma; Lora Escobar, Santiago José; Montecatine Alonso, Elena; Li, Tao; Acosta García, Héctor; Química Orgánica y Farmacéutica
Purpose The aim of this study was to review and compile the available information, in an easily accessible format, regarding the stability of thermolabile drugs at room temperature (22–25 °C), according to information contained in summary of product characteristics (SmPC), published literature, and information provided by the manufacturing pharmaceutical companies. Methods Drugs included in our hospital that required storage at a temperature between 2 and 8 °C were selected. Medications used in clinical trials, frozen drugs, and compounded formulations were excluded. The first source of information consulted for stability data was the SmPC. In case of no information available, published literature and gray literature were reviewed. If information was not found through these sources, the manufacturing laboratory was contacted. The results are shown in table format to make the information more manageable. The table contains the following information: Drug product, trade name, brand name (manufacturer), maximum stability at room temperature, and information source. Stability data from SmPC were included for all medications, and for those with additional information obtained through the sources used in the study, this was included in a separate column. Results A total of 203 thermolabile drugs were selected. Thirty seven (18.2%) had a stability of 24 h at room temperature, 36 (17.7%) had a stability of 48 h–1 week, 63 (31%) had a stability of 1 week–1 month, and 52 (25.6%) had a stability of more than 1 month. However, 12 drugs (6.3%) had a stability of less than 24 h, and 3 drugs (1.4%) had other stability data at room temperature. Stability information for 95 (46.7%) drugs was obtained from the SmPC, 56 (27.5%) from published literature, and 36 (26.2%) from manufacturers. In 21 of these cases, the stability information was valid exclusively for a specific case, with particular storage conditions and for a specific batch of the product. Conclusion The number and impact of thermolabile drugs have increased exponentially in recent years. The vast majority of these drugs maintain adequate stability at room temperature for an acceptable period of time, with some remaining stable for relatively long periods. To date, our study presents the largest dataset on the stability of these drugs. Therefore, the results of our study constitute a highly useful and up-to-date tool for saving time and money in hospital pharmacy units. Pharmaceutical manufacturers should consider publishing stability study results under non-recommended storage conditions in the SmPC.
Closed-loop biomaterial design: Diels-Alder hydrogels from renewable polymers for biomedical devices
(Elsevier, 2025-09) Díaz Carrasco, Fátima; Benito Hernández, Elena María; García Martín, María de Gracia; Paz Báñez, María Violante de; Química Orgánica y Farmacéutica; Agencia Estatal de Investigación. España; Junta de Andalucía
Guar gum (GG), a biodegradable and biocompatible polysaccharide, exhibits limited stability in its hydrogel form. To overcome this, semi-interpenetrating polymeric networks (semi-IPN) were engineered by synthesizing a Diels-Alder (DA) polymer (Polymer 1) from a difurfuryl monomer (Di-Fur, derived from L-tartaric acid) and a dimaleimide (Di-Mal, from 1,8-diamine-3,6-dioxaoctane) within a GG solution (Polymer 2). Controlled crosslinking was achieved by introducing a novel trifunctional crosslinker (Tri-Fur), containing three furan rings and synthesized from D-ribonolactone. By optimizing the Tri-Fur concentration, maximum crosslinking degrees (Xr) of 4 % and 10 % were attained, yielding GG-Xr4 and GG-Xr10, respectively. Polymer 1 demonstrated thermal degradation at 60 °C, releasing maleimide units that undergo rapid Michael addition, indicating reversible and self-healing properties. Rheological studies confirmed that the materials were gelatinous and stable for 14 days at 25 °C, maintaining integrity from 24 to 60 °C, with complex viscosity notably increasing between 24 °C and 37 °C (e.g., GG-Xr4: 139 to 619 Pa·s), supporting potential for injectable formulations. SEM revealed nanoporous structures (GG-Xr4: 530 nm mean pore size). The materials retained mucoadhesive properties and enabled drug loading and release, enhancing GG's biomedical and pharmaceutical potential.
Engineering Robust, Porous Guar Gum Hydrogels by One-Step Mild Synthesis: Impact of Porogen Choice on Rheology and Sustained Gastroretentive Amoxicillin Delivery
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-10-01) Díaz Carrasco, Fátima; Paz Báñez, María Violante de; Katavić, Matea; García Pulido, Estefanía; Santos Medina, Álvaro; Muíña Ramil, Lucía; García Martín, María de Gracia; Benito Hernández, Elena María; Química Orgánica y Farmacéutica; Ministerio de Ciencia e Innovación (MICIN). España; Junta de Andalucía
This study introduces a single-step method to synthesize guar gum-based interpenetrating polymer network (IPN) hydrogels, achieving simultaneous Diels–Alder crosslinking and amoxicillin (AMOX) encapsulation under mild conditions. To evaluate the influence of porogen addition on IPN structure, drug loading and release, twenty-one formulations were developed, including AMOX loading (25% or 40% w/w relative to the polymer) and biocompatible porogens incorporation [polyethylene glycol (PEG) or sucrose at 5%, 10%, or 50% w/w]. All crosslinked IPN hydrogels formed robust gels, unlike non-crosslinked controls. Porogen choice strongly influenced hydrogel performance: PEG quadrupled the swelling index while enhancing storage modulus (up to 10,054 Pa) and complex viscosity (up to 1302 Pa·s), whereas high sucrose concentrations produced soft, ductile networks with critical strains above 20% and swelling indices up to 1895%. All hydrogels released AMOX at levels above MIC50 for H. pylori. PEG-based IPN provided superior drug delivery profiles, with extended AMOX release (t50 up to 15.5 h at pH 5.0), while sucrose-rich matrices exhibited faster burst release and disintegration. Single-step (pre-loading) AMOX during synthesis improved release control compared to post-loading. These findings highlight the potential of one-pot IPN synthesis with porogen modulation offering a promising gastroretentive platforms for sustained AMOX delivery against H. pylori.
Hydroxytyrosyl Eicosapentaenoate as a Potential Antioxidant for Omega-3 Fatty Acids: Improved Synthesis and Comparative Evaluation with Other Natural Antioxidants
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-05-13) García Acosta, Natalia; Cert, Rosa; Jordán, Marta; Goya, Luis; Mateos, Raquel; Espartero Sánchez, José Luis; Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Ministerio de Ciencia e Innovación (MICIN). España
Hydroxytyrosol (HT), the primary phenolic compound in virgin olive oil, has notable cardiovascular benefits, particularly in preventing low-density lipoprotein (LDL) oxidation. However, its hydrophilicity limits its solubility and integration into lipid-based formulations. This study aimed to enhance its lipophilicity by synthesizing hydroxytyrosyl eicosapentaenoate (HT-EPA), a derivative of HT and eicosapentaenoic acid (EPA), using a one-step enzymatic catalysis with lipase B from Candida antarctica (CALB). The reaction, performed as a suspension of HT in ethyl eicosapentaenoate (Et-EPA) (1:9 molar ratio) under vacuum, achieved higher yields and shorter reaction times than previously reported, with a purity exceeding 98%, confirmed by 1H-NMR. For the first time, the antioxidant capacity of HT-EPA in comparison with other natural antioxidants was assessed using the FRAP assay, while its oxidative stability in an omega-3-rich oil matrix was evaluated via the Rancimat method. HT-EPA and hydroxytyrosyl acetate (HT-Ac) displayed antioxidant activity comparable to HT but significantly higher than α-tocopherol, a common food antioxidant. Given the scarcity of effective lipid-soluble antioxidants, HT-EPA represents a promising candidate for omega-3 nutraceuticals, offering enhanced stability and potential health benefits. This study provides a simple, efficient, and scalable strategy for developing functional lipid-based formulations with cardioprotective potential by improving HT solubility while preserving its antioxidant properties.
Nanoparticle Architecture Governing Antibacterial and Osteoinductive Responses in Bone-Integrating Implants
(MDPI, 2025-09-16) Gaviria, Juliana; Gaviria, Veronica; Silva, Kamilla V. R. A.; Alcudia Cruz, Ana; Padrón-Hernández, Eduardo; Torres Hernández, Yadir; Química Orgánica y Farmacéutica; Ingeniería y Ciencia de los Materiales y del Transporte; FQM408: Química Farmacéutica Aplicada; TEP123: Metalurgia e Ingeniería de los Materiales
Metallic nanoparticles (MNPs) have emerged as leading candidates in biomedical applications owing to their unique physicochemical properties and dual functionality, combining potent bactericidal and osteoinductive effects. These bioactivities are intricately governed by structural parameters such as size, shape, crystallinity, and chemical composition, which collectively dictate their interactions with biological systems. These interactions affect key mechanisms including oxidative stress induction, membrane disruption, and modulation of cellular signaling pathways. Despite considerable progress, a comprehensive understanding of the structure property–activity-specific structural relationship in MNPs remains incomplete, hindering the rational design of optimized nanomaterials. This review critically examines recent advances in elucidating the bactericidal and osteoinductive mechanisms of MNPs, with a particular focus on the role of structural determinants. Furthermore, current challenges and future directions for tailoring nanoparticle architecture to enhance clinical performance are discussed. To address this, we conducted a systematic review of the literature published between 2005 and 2024 using Web and Web of Science direct and Scopus databases. Our analysis is structured around a structure →mechanism→outcome perspective, linking nanoparticle features to biological responses. Key insights include the following: (i) nanoparticles below ~20 nm generally enhance bacterial efficiency through enhanced membrane disruption; (ii) surface hydroxyl density above critical thresholds promotes osteogenic signaling; and (iii) safe concentration windows remain narrow, highlighting the importance of dose optimization. We conclude by discussing the translational challenges and future directions for tailoring nanoparticle architectures to advance clinical applications.
Infiltrated 3D-printed zirconia scaffolds with biodegradable and bioactive polymer blend to improve their osseointegration
(Elsevier, 2025-12) Delgado-Pujol, Ernesto J.; Razavi, Ali; Begines Ruiz, Belén; Llanes, Luis; Morales, Miguel; Alcudia Cruz, Ana; Torres Hernández, Yadir; Fargas, Gemma; Ingeniería y Ciencia de los Materiales y del Transporte; Química Orgánica y Farmacéutica; Ministerio de Ciencia e Innovación (MICIN). España; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; TEP123: Metalurgia e Ingeniería de los Materiales; FQM408: Química Farmacéutica Aplicada
Bone defects and skeletal disorders continue to demand advanced biomaterials that combine mechanical strength with enhanced bioactivity and customizability. While yttria-stabilized zirconia (YSZ) offers excellent mechanical properties and biocompatibility, its bioinert nature and processing challenges limit its effectiveness for patient-specific bone implants. This study addresses this gap by developing novel polymer-infiltrated ceramic network (PICN) scaffolds based on 3D-printed porous YSZ fabricated via Direct Ink Writing (DIW). The scaffolds were infiltrated with biodegradable polycaprolactone (PCL)/polyvinyl alcohol (PVA) blends loaded with nanohydroxyapatite (nHA) to impart bioactivity and tunable degradation. Scaffold designs with 40 % and 60 % infill were evaluated for infiltration efficiency, mechanical performance, degradation behavior, and apatite formation capacity. Results demonstrated high infiltration rates (up to 96 %, particularly in 40 % infill scaffolds), mechanical integrity comparable to cancellous bone (compressive strength within the range of 2–12 MPa), and enhanced in vitro apatite formation, especially for scaffolds with an 80:20 PCL/PVA blend containing 15 % nHA. The degradation analysis indicated that higher PVA content accelerated resorption, with the 50:50 blend showing faster surface changes, while the 80:20 blend maintained gradual porosity increase aligned with tissue replacement. Overall, this work presents a feasible strategy for fabricating patient-specific ceramic scaffolds with enhanced osseointegration potential, thereby bridging the gap between mechanical stability and biological functionality for future bone and dental implant applications.
Hydroxytyrosol Bioavailability: Unraveling Influencing Factors and Optimization Strategies for Dietary Supplements
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-09-12) Jordán, Marta; García-Acosta, Natalia; Espartero Sánchez, José Luis; Goya, Luis; Mateos, Raquel; Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España
Hydroxytyrosol (HT) is a major phenolic compound in olives and extra virgin olive oil (EVOO), known for its antioxidant, anti-inflammatory, and cardiometabolic properties. The European Food Safety Authority (EFSA) has approved a health claim for the protection of LDL particles from oxidative damage only when HT is consumed within EVOO, which limits its direct use in supplements or functional foods. Since its biological effects depend on absorption, distribution, metabolism, and excretion (ADME), understanding how formulation and delivery strategies influence bioavailability is essential. HT is mainly present as secoiridoid derivatives in EVOO, whereas in supplements, it often appears in its free form, potentially affecting its metabolic fate. This review summarizes human studies on HT bioavailability from EVOO, isolated supplements, and enriched foods, and examines how matrix type, chemical modifications of HT, and advanced delivery systems, such as emulsions, encapsulation, and vesicular carriers, modulate absorption and metabolism. The gut microbiota is highlighted as an emerging factor in HT biotransformation, although its role remains underexplored. Further well-designed human studies are needed to guide the development of nutraceutical formulations capable of replicating the health benefits of EVOO beyond its natural matrix.
Monovalent glycoconjugates of sulforaphane prevent inflammation induced by lipopolysaccharide in human dendritic cells by inhibiting NF-ĸB signalling pathway
(John Wiley and Sons Inc, 2025-11) Leiva‐Castro, Camila; Múnera‐Rodríguez, Ana Maria; Martínez Bailén, Macarena; Carmona Asenjo, Ana Teresa; López Enríquez, Soledad; Palomares Jerez, María Francisca; Química Orgánica y Farmacéutica; Química Orgánica; Bioquímica Médica y Biología Molecular e Inmunología; Ministerio de Ciencia e Innovación (MICIN). España; Universidad de Sevilla
Background and Purpose: Sulforaphane (SFN) has notable health benefits but faces challenges due to its poor solubility and delivery. This study investigates SFN-glycoconjugates effects on lipopolysaccharide (LPS)-induced inflammation in dendritic cells (DCs). With the aiming to enhance their therapeutic potential against inflammatory diseases. Novel monovalent SFN-glycoconjugates with mannose (Man) and fucose (0Fuc) were developed and tested for their anti-inflammatory and immune-modulatory properties in DCs from healthy donors under chronic LPS exposure. Experimental Approach: By leveraging therapeutic strategies, SFN-glycoconjugates significantly improved the solubility and bioavailability of SFN, thereby overcoming the limitations of traditional delivery methods. Monocyte-derived DCs were treated with SFN-glycoconjugates and subsequently exposed to a chronic inflammatory environment induced by LPS. Key Results: Our results showed that SFN-glycoconjugates enhance effectiveness in suppressing inflammation by targeting the p65 NF-κB pathway, without affecting MAPK signalling. SFN-glycoconjugates induce a tolerogenic immune response, characterized by increased IL-10 production and enhanced regulatory T- and B-cell proliferation. These effects surpass those of p65 NF-κB inhibition alone, highlighting a distinct and potent regulatory mechanism independent of MAPK pathways. Conclusion and Implications: The integration of food therapeutic strategies not only enhances the stability and delivery of bioactive compounds but also broadens their potential applications in functional foods and therapeutic approaches. In particular, SFN-glycoconjugates represent a promising option as biologically active compounds for inflammatory diseases, offering enhanced anti-inflammatory and immunomodulatory effects through optimized delivery systems and the activation of specific molecular pathways.
Synthesis and in vitro cytotoxicity of benzoxazole-based PPARα/γ antagonists in colorectal cancer cell lines
(Wiley, 2024-09) Moreno Rodríguez, Nazaret; Laghezza, Antonio; Cerchia, Carmen; Sokolova, Darina V.; Spirina, Tatiana S.; De Filippis, Barbara; Romanelli, Virgilio; Recio Jiménez, Rocío; Fernández Fernández, Inmaculada; Loiodice, Fulvio; Pokrovsky, Vadim S.; Ammazzalorso, Alessandra; Lavecchia, Antonio; Química Orgánica y Farmacéutica; RUDN University; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Ministry of Education. Italy
A series of benzoxazole-based amides and sulfonamides were synthesized and evaluated for their human peroxisome proliferator-activated receptor (PPAR)α and PPARγ activity. All tested compounds showed a dual antagonist profile on both PPAR subtypes; based on transactivation results, seven compounds were selected to test their in vitro antiproliferative activity in a panel of eight cancer cell lines with different expression rates of PPARα and PPARγ. 3f was identified as the most cytotoxic compound, with higher potency in the colorectal cancer cell lines HT-29 and HCT116. Compound 3f induced a concentration-dependent activation of caspases and cell-cycle arrest in both colorectal cancer models. Docking experiments were also performed to shed light on the putative binding mode of this novel class of dual PPARα/γ antagonists.
Exploring the Broad-spectrum Activity of Carbohydrate-based Iberin Analogues: From Anticancer Effect to Antioxidant Properties
(Elsevier, 2025) Prieto Ramírez, Luis Alberto; Khiar Fernández, N.; Calderón Montaño, José Manuel; López Lázaro, Miguel; Lucía Tamudo, J.; Nogueira, J. J.; León, R.; Moreno Rodríguez, Nazaret; Valdivia Giménez, Victoria Esther; Recio Jiménez, Rocío; Fernández Fernández, Inmaculada; Química Orgánica y Farmacéutica; Farmacología; Ministerio de Ciencia e Innovación (MICIN). España; Universidad de Sevilla
Iberin is a lower homologue of sulforaphane (SFN) which has shown effectiveness in addressing various pathologies, including its anti-inflammatory properties, antitumor activity against various cancers, and antimicrobial effects. Building on this activity, a series of carbohydrate-based analogues of the natural isothiocyanate (ITC) iberin were synthesized, and their anticancer and antioxidant activities were evaluated. Cytotoxicity studies on three cancer cell lines using Resazurin assay demonstrated significant cytotoxic activity, particularly against bladder cancer. The sulfonyl derivatives exhibited the most potent effects, with IC50 values comparable to those of reference natural isothiocyanates (from 10 to 20 μM). Computational simulations support the hypothesis that carbohydrate-based ITCs can interact with STAT3's SH2 domain in a manner similar to SFN, laying the groundwork for their potential development as STAT3-targeted anticancer agents. The antioxidant potential of these compounds was assessed by their ability to activate the Nrf2 factor, yielding CD values (concentration required to double luciferase activity compared to basal conditions) between 1.55 and 10.36 μM, without cytotoxicity at these concentrations. Notably, the phenylsulfone derivative 22β displayed slightly higher or comparable antioxidant activity to that of natural isothiocyanates. Based on these findings, this phenylsulfone analogue was selected as the optimal compound due to its dual anticancer and antioxidant activities. An additional advantage of this carbohydrate-based ITC is that it is a solid compound, making it easier to handle than natural isothiocyanates, which are typically liquids.
Virgin olive oil polyphenol hydroxytyrosol acetate inhibits in vitro platelet aggregation in human whole blood: comparison with hydroxytyrosol and acetylsalicylic acid
(2008-09-08) González Correa, José Antonio; López Villodres, Juan Antonio; Asensi, Rocío; Espartero Sánchez, José Luis; Rodríguez Gutiérrez, Guillermo; Cruz, José Pedro de la; Química Orgánica y Farmacéutica; Ministerio de Ciencia y Tecnología (MCYT). España
Hydroxytyrosol acetate (HT-AC) is a polyphenol present in virgin olive oil (VOO) at a proportion similar to hydroxytyrosol (HT) (160–479 μmol/kg oil). The present study was designed to measure the in vitro platelet antiaggregating activity of HT-AC in human whole blood, and compare this effect with that of HT and acetylsalicylic acid (ASA). The experiments were designed according to the standard procedure to investigate the activity of ASA. HT-AC and HT inhibited platelet aggregation induced by ADP, collagen or arachidonic acid in both whole blood and platelet-rich plasma (PRP). ASA and HT-AC had a greater effect in whole blood than in PRP when ADP or collagen was used as inducer. ASA and HT-AC had a greater effect in PRP+leucocytes than in PRP alone. All three compounds inhibited platelet thromboxane B2 and leucocyte 6-keto-prostaglandin F1α (6-keto-PF1α) production. The thromboxane/6-keto-PGF1α inhibition ratio (as an indirect index of the prostanoid equilibrium) was 10·8 (se 1) for HT-AC, 1·0 (se 0·1) for HT and 3·3 (se 0·2) for ASA. All three compounds stimulated nitric oxide production, although HT was a weaker effect. In our experiments only concentrations higher than 500 μm (HT) or 1 mm (HT-AC and ASA) inhibited 3-nitrotyrosine production. All three compounds inhibited the production of TNFα by leucocytes, with no significant differences between them. In quantitative terms HT-AC showed a greater antiplatelet aggregating activity than HT and a similar activity to that of ASA. This effect involved a decrease in platelet thromboxane synthesis and an increase in leucocyte nitric oxide production.
Hydrogels and Nanogels: Pioneering the Future of Advanced Drug Delivery Systems
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-02-07) Delgado-Pujol, Ernesto J.; Martínez Muñoz, Guillermo; Casado Jurado, David; Vázquez Cabello, Juan; León Barberena, Jesús; Rodríguez Lucena, David; Torres Hernández, Yadir; Alcudia Cruz, Ana; Begines Ruiz, Belén; Química Orgánica y Farmacéutica; Ingeniería y Ciencia de los Materiales y del Transporte; Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España
Conventional drug delivery approaches, including tablets and capsules, often suffer from reduced therapeutic effectiveness, largely attributed to inadequate bioavailability and difficulties in ensuring patient adherence. These challenges have driven the development of advanced drug delivery systems (DDS), with hydrogels and especially nanogels emerging as promising materials to overcome these limitations. Hydrogels, with their biocompatibility, high water content, and stimuli-responsive properties, provide controlled and targeted drug release. This review explores the evolution, properties, and classifications of hydrogels versus nanogels and their applications in drug delivery, detailing synthesis methods, including chemical crosslinking, physical self-assembly, and advanced techniques such as microfluidics and 3D printing. It also examines drug-loading mechanisms (e.g., physical encapsulation and electrostatic interactions) and release strategies (e.g., diffusion, stimuli-responsive, and enzyme-triggered). These gels demonstrate significant advantages in addressing the limitations of traditional DDS, offering improved drug stability, sustained release, and high specificity. Their adaptability extends to various routes of administration, including topical, oral, and injectable forms, while emerging nanogels further enhance therapeutic targeting through nanoscale precision and stimuli responsiveness. Although hydrogels and nanogels have transformative potential in personalized medicine, challenges remain in scalable manufacturing, regulatory approval, and targeted delivery. Future strategies include integrating biosensors for real-time monitoring, developing dual-stimuli-responsive systems, and optimizing surface functionalization for specificity. These advancements aim to establish hydrogels and nanogels as cornerstones of next-generation therapeutic solutions, revolutionizing drug delivery, and paving the way for innovative, patient-centered treatments.
Lyocell/silver knitted fabrics for prospective diabetic foot ulcers treatment: Effect of knitting structure on bacteria and cell viability
(Elsevier, 2025-04-01) Tavares, Tânia D.; Ribeiro, Artur; Bengoechea Ruiz, Carlos; Rocha, Diana; Alcudia Cruz, Ana; Begines Ruiz, Belén; Silva, Carla Carolina; Antunes, Joana C.; Felgueiras, Helena P.; Ingeniería Química; Química Orgánica y Farmacéutica; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Fundación Nacional de Ciencia y Tecnología de Portugal (FCT)
Diabetic foot ulcers (DFUs) are a serious complication of diabetes, often resulting in infections and further health deterioration. Thus, the development of an approach combining different therapies in just one formulation to treat DFUs remains very challenging. Silver-plated polyamide fibers offer antimicrobial properties, while lyocell provides biodegradability, biocompatibility and moisture management abilities. In this sense, the present study explores the potential of lyocell/silver-plated polyamide fabrics as part of advanced wound dressings designed to improve DFU treatment. The most common knitting structures, namely single jersey, “false” rib 1 × 1, single pique, and “false” interlock, were selected for combining the yarns and successfully processed using seamless technology. The knitted fabrics were then subjected to a comprehensive analysis of their physical, chemical, and thermomechanical properties, demonstrating that the samples met the criteria for effective wound dressing development. Their antimicrobial efficacy was evaluated against DFU-associated Gram-negative pathogens, Escherichia coli and Pseudomonas aeruginosa, showing strong antimicrobial activity for up to 24 h, with total inhibition in some cases (jersey, pique and interlock structures for E. coli and interlock structure for P. aeruginosa). Antioxidant testing revealed DPPH reduction of 61.7 ± 14.4 %. Biocompatibility was assessed using keratinocytes HaCaT cell lines, showing that knitted fabrics with up to 1.46 % silver content did not harm mammalian cells. In general, interlock structure revealed the most promising features, including mechanical performance, and air and water vapor permeability, for promoting optimal wound healing conditions.
Enhanced porous titanium biofunctionalization based on novel silver nanoparticles and nanohydroxyapatite chitosan coatings
(Elsevier, 2025-04) Castillejo, Ana; Martínez Muñoz, Guillermo; Delgado-Pujol, Ernesto J.; Villalobo Polo, Eduardo; Carrillo de la Fuente, Francisco; Casado Jurado, David; Pérez Bernal, Juan Luis; Begines Ruiz, Belén; Torres Hernández, Yadir; Alcudia Cruz, Ana; Química Orgánica y Farmacéutica; Ingeniería y Ciencia de los Materiales y del Transporte; Química Analítica; Ingeniería Química; Microbiología; Ministerio de Ciencia e Innovación (MICIN). España
Titanium is widely used for implants however it presents limitations such as infection risk, stress shielding phenomenon, and poor osseointegration. To address these issues, a novel approach was proposed that involves fabricating porous titanium substrates, to reduce implant stiffness, minimizing stress shielding and bone resorption, and applying polymeric coatings to improve bioactivity. Composite coating prepared from chitosan, silver nanoparticles, and nanohydroxyapatite was optimized to enhance antibacterial properties and promote osseointegration. Chitosan with 80.5 % of deacetylation degree was used to prepare composites with diverse compositions, including different methodologies of adding silver nanoparticles, with silver concentrations below toxic level. Antibacterial activity was tested with three different strains, including Gram+ and Gram− bacteria, demonstrating excellent inhibition after 21 days. In addition, the induction of hydroxyapatite formation was investigated. Finally, the optimal porous metallic substrate that exhibited a more suitable stiffness (29 GPa) (close to the cortical bone tissue they intend to replace) was chosen to be infiltrated with the selected composites. In summary, this synergistic approach based on the combination of porous titanium substrates with 60 vol% porosity and a 355–500 μm pore size distribution coated with 3%CS-nHA-AgNPs-TPP-AgNPsbath composite provided a potential solution to provide implants with improved biomechanical balance and biofunctionality.

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