Artículos (Química Orgánica y Farmacéutica)

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

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Use of the MOF NU-1000 as a Drug Delivery System for the Antineoplastic Drug Mitoxantrone
(MDPI, 2026-05-28) Alfonso, Daniel R.; Moscoso, Francisco G.; Rodríguez Lucena, David; Roales Batanero, Javier; Carrillo Carrión, Carolina; Cascajo Almenara, María Victoria; Santos Ocaña, Carlos; Pedrosa, José M.; Química Orgánica y Farmacéutica; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; European Union (UE); Junta de Andalucía
Metal–organic frameworks (MOFs) offer unique opportunities for drug delivery due to their high porosity and the possibility of hosting large drug molecules within well-defined pore systems. In this work, the zirconium-based MOF NU-1000 was investigated as a carrier for the antineoplastic drug mitoxantrone (MTX). NU-1000 particles were synthesized and characterized by PXRD, SEM, and DLS, confirming their crystallinity, morphology, and size distribution. MTX loading was achieved by aqueous incubation and quantified by UV-Vis spectroscopy and thermogravimetric analysis, yielding a high loading capacity of ~40–43 wt%, with most of the uptake occurring within the first three hours. Structural characterization demonstrated that the MOF preserves its crystallinity and morphology after drug incorporation, while the DLS results suggest that MTX is mainly accommodated within the internal pore system. To improve stability under physiological conditions, the composite was coated with NH2-PEG-NH2, resulting in PEG@MTX@NU-1000 particles with enhanced stability in phosphate-buffered saline. Cytotoxicity assays in HeLa cells showed that the PEGylated carrier is largely biocompatible, while PEG@MTX@NU-1000 exhibits a significantly enhanced antiproliferative effect compared to free MTX at short incubation times. These results demonstrate that NU-1000 is a promising platform for MTX delivery, combining high loading capacity, structural stability after PEGylation, and improved short-term therapeutic performance.
Synthesis and investigation of selective human carbonic anhydrase IX, XII inhibitors using coumarins bearing a sulfonamide or biotin moiety
(Elsevier, 2024-12-01) Begines Aguilar, Paloma; Bonardi, Alessandro; Giovannuzzi, Simone; Nocentini, Alessio; Gratteri, Paola; Luca, Viviana de; González-Bakker, Aday; Padrón, José M.; Capasso, Clemente; Supuran, Claudiu T.; Química Orgánica y Farmacéutica
The role of carbonic anhydrases isoforms (CAs) IX and XII in the pathogenesis and progression of many types of solid tumors is well known. In this context, selective CA inhibitors (CAIs) towards the mentioned isoforms is a validated strategy for the development of agents to target cancer. For this purpose, novel coumarin derivatives based on the hybridization with arylsulfonamide or biotin scaffolds were synthesized and testing as inhibitors of four different human carbonic anhydrases isoforms: hCA I, II, IX and XII. Coumarin-sulfonamide derived 27, with a thiourea moiety and triazole as linker, showed the highest inhibition activity against hCA XII with an inhibition constant (KI) of 7.5 nM and afforded a very good selectivity over hCA I. Compound 32 was the most potent inhibitor against hCA IX (KI = 6.3 nM), 4-fold stronger than the drug acetazolamide AAZ (KI = 25 nM), used herein as a reference compound, and showed remarkable selectivity over hCA I and II. The coumarin-biotin derivatives 37 ̶ 39 showed outstanding selectivity towards on-target enzymes (hCA IX and XII) and appear as plausible leads for designing of CAIs.
Strong Antiproliferative Activity Observed in Hammett-Guided Electronic Modulation of GPx-Mimetic Pathways in Aryl Selenoureas
(MDPI, 2026) Begines Aguilar, Paloma; Pérez-Lage, Clara I.; Puerta, Adrián; Padrón, José M.; López López, Óscar; Fernández-Bolaños Guzmán, José María; Química Orgánica y Farmacéutica; Química Orgánica; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía
Organoselenium chemistry has undergone remarkable development over the past five decades, evolving from its initial association with high toxicity into a field with pivotal contributions to materials science, organic synthesis, catalysis, and Medicinal Chemistry. Among the diverse biological activities displayed by organoselenium compounds, their redox behaviour is particularly compelling, as many of these molecules act as efficient mimetics of the antioxidant enzyme glutathione peroxidase (GPx). In this work, we investigated the GPx-like activity of a series of N,N′-diaryl selenoureas toward the depletion of H2O2 and cumene hydroperoxide (CumOOH) as model ROS. Their reactivity was correlated with the electronic nature of the aryl substituents using a Hammett-type analysis, revealing a strong dependence of the reaction rate on remote electronic perturbations within the aromatic ring. Combined UV and NMR studies provided mechanistic evidence supporting a catalytic cycle in which selenoureas, operating at sub-stoichiometric loadings (1 mol%) and using a thiol as a cofactor-like molecule, can be used to efficiently scavenge ROS with half-lives of only a few minutes (~10–60 min). Furthermore, these selenoureas exhibited potent antiproliferative activity across several human solid tumour cell lines. Overall, these results offer mechanistic insight into the ROS-eliminating pathways of selenoureas and highlight their potential as chemopreventive or anticancer agents.
Metabolically-Driven Active Targeting of Magnetic Nanoparticles Functionalized with Glucuronic Acid to Glioblastoma: Application to MRI-Tracked Magnetic Hyperthermia Therapy
(Wiley, 2025) Caro, Carlos; Páez-Muñoz, José María; Pernia Leal, Manuel; Carayol, Marta; Feijoo Cuaresma, Mónica; García Martín, María L.; Química Orgánica y Farmacéutica; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; Junta de Andalucía; Junta de Andalucía
Cancer continues to pose a major global health challenge, with malignant brain tumors, particularly Glioblastoma Multiforme (GBM), assuming a prominent role due to their incurable nature. The need for new strategies to combat this devastating tumor is therefore paramount. Nanotechnology offers unique opportunities to develop innovative and more effective therapeutic approaches. However, most nanosystems developed to treat GBMs, particularly those based on metallic nanoparticles (NPs), have proven unsuccessful due to their inability to efficiently target these tumors, as the restrictions imposed by the blood-brain tumor barrier (BBTB) make them particularly inaccessible. Here, we present an innovative strategy to efficiently target metallic NPs to GBMs through glucose transporters (GLUT) overexpressed on the endothelial cells of GBM microvasculature, particularly GLUT1. Specifically, Iron Oxide Nanoparticles (IONPs) are functionalized with glucuronic acid to promote GLUT-mediated transport, which is drastically boosted by inducing mild hypoglycemia. This metabolically-driven active targeting strategy has yielded unprecedented efficacy in targeting metallic NPs to GBMs. Moreover, these IONPs, designed to act as magnetic hyperthermia (MH) mediators, have been used to conduct a proof-of-concept preclinical study on MRI-tracked MH therapy following intravenous administration, resulting in significant tumor growth delay. Our findings lay the ground for developing alternative therapeutic strategies to combat GBM.
Protein corona as the key factor governing the in vivo fate of magnetic nanoparticles
(Royal Society of Chemistry, 2025) Avasthi, Ashish; Fernández-Afonso, Yilian; Gutiérrez, Lucía; Fuente, Jesús M. de la; Pernia Leal, Manuel; Caro, Carlos; García Martín, María Luisa; Química Orgánica y Farmacéutica; Junta de Andalucía; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. España; European Union (UE); Instituto de Salud Carlos III; Gobierno de Aragón
Advancements in the field of nanotechnology have opened a myriad of avenues for diverse applications. One such avenue is the role of nanoparticles (NPs) in the healthcare sector, whether it is drug targeting, drug delivery, or imaging, offering unprecedented prospects for improving targeted interventions along with minimal toxicity. Meanwhile, the intricate interplay between the characteristics of NPs and the ensuing biological cross-talk has engendered profound interest among scientists. Amidst the determinants shaping the behavior of NPs within the biological milieu, the biodistribution and pharmacokinetics of the NPs stand as pivotal factors intricately intertwined with their core size, hydrodynamic diameter (HD), coating ligands, as well as the proteins they interact with, forming the protein corona. This article compiles and analyzes the data to decipher the factors determining the fate of NPs in vivo. For this purpose, two IONPs with differing core sizes (≈ 4 nm and ≈ 8 nm) but coated with the same gallol-PEG ligand (GA-PEG3000-OH) and possessing very similar HDs (≈ 35 nm) as well as relaxivity (≈ 100 mM-1•s-1) were selected. Following physicochemical characterization, both protein coronas were thoroughly analyzed, revealing differences in both the composition and the relative abundance. Later, after determining the negligible cytotoxicity of both NPs, they were intravenously injected into Balb/c mice to evaluate their in vivo biodistribution and pharmacokinetics using MRI. Additionally, biodistribution was further investigated ex vivo by quantitative magnetic analysis of blood and tissues, alongside histological evaluation. Our results evidenced that the protein corona, rather than core size or hydrodynamic diameter, is the determining factor governing the in vivo fate of magnetic NPs.
Minimum Perceptual Time (MPT). Repeatability and reproducibility of variables applied to "Sports Vision"
(Springer, 2025) Ríder-Vázquez, Antonio; Vega Holm, Margarita; Sánchez González, María del Carmen; Gutiérrez Sánchez, Estanislao; Física de la Materia Condensada; Química Orgánica y Farmacéutica; Cirugía
Purpose: “Minimum Perceptual Time” (MPT) is the ability to take the most visual information in the least time. The purpose of the study was to assess intraobserver and interobserver repeatability of a MPT measurement method by using COI-SV® software and to analyze the possible influence of age and sex. Methods: MPT was measured in 79 participants by using COI-SV® software. Visual acuity was 20/80 (2.50m) and numbers were gradually increasing in quantity and decreasing in exposure time. The most quantity of numbers and the least time was written down. To assess intraobserver and interobserver repeatability, a protocol based on repeating the test 4 times (2 intrasession and 2 intersessions with 2 examinators) was established. Comparison of means and Spearman correlation were performed to evaluate the influence of sex and age. It was investigated inter and intraexaminer variability using repeatability indices, as well as Bland-Altman analysis to define limits of agreement. Results: A total of 79 participants were included (mean age 32.8±11.95 years, range 19–64 years). Regarding sex, there were no significant differences between men and women (p= 0.080), whereas age and MPT had an inverse correlation (p=0.01). Interexaminer and intraexaminer repeatability proved to be moderate to good in all methods. Bland-Altman showed difference between sessions was 0.259 ± 2.189 (-4.030 and +4.549) and difference between examiners was -0.519 ± 2.104 (-4.642 and +3.604). Conclusion: MPT measurements with COI-SV® software evidenced moderate to good repeatability and observers` independent result, so it could be included in optometric examinations.
Surface chemistry matters: how ligand–core interactions control magnetic and thermal properties of iron oxide nanoparticles?
(Elsevier, 2026-03-21) Gimeno Ferrero, Raúl; García-Martín, María Luisa; Pernia Leal, Manuel; Química Orgánica y Farmacéutica; Junta de Andalucía; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. España
Iron oxide nanoparticles (IONPs) are one of the most developed magnetic nanomaterials due to their potential applications as magnetic resonance imaging (MRI) contrast agents and in magnetic hyperthermia. Most studies have focused on developing synthetic methods to control particle size and morphology to enhance their magnetic performance. In this work, the influence of surface chemistry on the magnetic properties of IONPs by employing a series of purified PEGylated ligands with systematic variations in their anchoring and terminal groups is reported. The ligands were synthesized and used to functionalize IONPs via a ligand exchange approach. These functionalized IONPs exhibited marked differences in their physicochemical and magnetic properties depending on the nature of the ligand. Specifically, the efficiency as MRI T2 contrast agents and the heating capacity under alternating magnetic fields were found to correlate with the anchor group-Fe binding constant, the absolute value of the ξ-potential, and the presence of surface impurities. These findings reveal that subtle chemical changes in the surface coating exert a crucial and quantifiable influence on the overall magnetic performance. This work highlights surface engineering as a rational strategy for developing IONPs with enhanced magnetic properties.
Design and Characterization of Gelatin-Based Interpenetrating Polymer Networks for Biomedical Use: Rheological, Thermal, and Physicochemical Evaluation
(Multidisciplinary Digital Publishing Institute (MDPI), 2026-01-10) Grosso, Roberto; Díaz-Carrasco, Fátima; Vidal-Nogales, Elena; Paz Báñez, María Violante de; Díaz-Blanco, M. Jesús; Benito Hernández, Elena María; Química Orgánica y Farmacéutica; Ministerio de Ciencia e Innovación (MICIN). España; Junta de Andalucía
Tissue engineering is a multidisciplinary field that aims to address tissue and organ failure by integrating scientific, engineering, and medial expertise. Gelatin is valued in this field for its biocompatibility; however, it faces thermal and mechanical weaknesses that limit its biomedical utility. This work proposes a strategy for improving gelatin properties by fabricating semi-interpenetrating polymer networks via in situ Diels–Alder crosslinking within gelatin colloidal solutions. Ten systems with variable polymer concentrations (2–4%) and crosslinking degrees (2–5%) were prepared and characterized. Rheological analysis revealed that elastic modulus, zero-shear viscosity, and complex viscosity were substantially enhanced, being especially dependent on the crosslinking degree, while critical strain values mostly depended on gelatin concentration. The incorporation of a synthetic Diels–Alder-crosslinked network also improved the thermal stability of gelatin hydrogels, particularly at physiological temperatures. Additionally, these systems exhibit favorable buoyancy, swelling and biodegradation profiles. Collectively, the resultant hydrogels are cytocompatible, solid-like, and mechanically robust, allowing for further tunability of their properties for specific biomedical uses, such as injectable matrices, load-bearing scaffolds for tissue repair, and 3D bioinks.
NRF2 as a therapeutic target in dermatological disorders: mechanisms and molecules
(MDPI, 2026-03-17) Khiar-Fernández, Ismael; Khiar-Fernández, Nora; Pereyra-Rodríguez, José-Juan; Fernández Fernández, Inmaculada; Medicina; Química Orgánica y Farmacéutica; ERDF/EU; Universidad de Sevilla; FQM102: Estereoquímica y Síntesis Asimétrica
The nuclear factor erythroid 2–related factor 2 (NRF2) is a master transcription factor that orchestrates cellular defense against oxidative and electrophilic stress. Dysregulation of the KEAP1–NRF2–ARE pathway has been implicated in several dermatological disorders, including vitiligo, psoriasis, atopic dermatitis, photoaging, and radiation dermatitis. This review summarizes recent advances in the understanding of NRF2 activation mechanisms and highlights pharmacological and natural compounds with potential dermatological applications. A comprehensive analysis of natural, semisynthetic, and synthetic NRF2 modulators is provided, describing their chemical structures, synthetic approaches, mechanisms of action, preclinical and clinical evidence, and therapeutic relevance for skin disorders. Multiple classes of NRF2 activators, including isothiocyanates such as sulforaphane, triterpenoids such as omaveloxolone, flavonoids including baicalein and apigenin, alkaloids such as berberine, glycosides like afzelin and paeoniflorin, stilbenoids such as tapinarof, and α,β-unsaturated fumaric acid esters such as dimethyl fumarate, have demonstrated antioxidant, anti-inflammatory, and cytoprotective effects in keratinocytes and melanocytes. Some of these agents, particularly dimethyl fumarate and tapinarof, have advanced to clinical development or commercialization, whereas others remain at the preclinical stage but show encouraging results in animal models and cell culture systems. Overall, pharmacological activation of NRF2 represents a promising therapeutic strategy to counteract oxidative stress–driven skin damage and inflammation; however, continued translational and clinical research is required to optimize formulations, dosing regimens, and safety profiles for integration into dermatological practice.
Engineering TNZT-coated titanium scaffolds via additive manufacturing and magnetron sputtering for bone tissue replacement
(Elsevier, 2026-02-15) Vilella, Tània; Delgado-Pujol, Ernesto J.; García-Hernández, Celia; Fargas Ribas, Gemma; Alfonso, Conrado R.M.; Rodríguez, Daniel; García Cabezón, Cristina; Alcudia Cruz, Ana; Sánchez López, Juan Carlos; Torres Hernández, Yadir; Ingeniería y Ciencia de los Materiales y del Transporte; Química Orgánica y Farmacéutica; Generalitat de Catalunya; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Ministerio de Ciencia e Innovación (MICIN). España; TEP123: Metalurgia e Ingeniería de los Materiales; FQM408: Química Farmacéutica Aplicada
The biomechanical behavior and corrosion phenomena of porous metallic implants can compromise their clinical success. This work proposes modifying the surface of c.p. titanium scaffolds manufactured by 3D-printing (Direct Ink Writing), depositing a thin film of a β-Ti alloy (Ti-35Nb-7Zr-5Ta) using the High-Power Impulse Magnetron Sputtering (HiPIMS) technique. The versatility of this technique has enabled the fabrication of conformal coatings with uniform thickness, excellent adhesion, a nanorough surface, and a homogeneous columnar distribution. Regarding the biofunctional behavior of the coatings, contact angle measurements and a comprehensive electrochemical study (including impedance spectroscopy, open-circuit potential, and anodic polarization) were performed in artificial saliva. The results are discussed in terms of 1) the potential of the HiPIMS technique; and 2) the role of the coating (effect on stress shielding, improved corrosion resistance, and fatigue life potential). Electrochemical measurements demonstrate the effectiveness of the coating in improving corrosion resistance. In particular, the corrosion current density decreased from 1.62 ± 0.06 μA/cm2 for uncoated scaffolds to 0.31 ± 0.01 μA/cm² after coating. At the same time, the polarization resistance increased nearly fivefold (from 0.84 × 10⁵ to 3.72 × 10⁵ Ω·cm²), confirming the protective effect of the TNZT film. The scaffold porosity favors bone ingrowth, while the reduced Young's modulus of the HiPIMS-deposited TNZT coating minimizes bone resorption. Moreover, its higher nanohardness suggests a potential increase in fatigue resistance. Finally, the synergistic combination of DIW-engineered porosity and a compact HiPIMS-deposited TNZT film will successfully alleviate stress shielding while enhancing corrosion resistance and biofunctional compatibility.
Potent Nrf2-Inducing C6-Isothiocyanate Glucose Derivatives with Dual Antioxidant and Antitumor Activity
(Multidisciplinary Digital Publishing Institute (MDPI), 2026-01-18) Prieto, Luis Alberto; Khiar-Fernández, Nora; Calderón-Ruiz, Rocío; Giraud, Emelyne; Calderón Montaño, José Manuel; Lucia-Tamudo, Jesús; León, Rafael; Pérez Simón, José Antonio; López Lázaro, Miguel; Torre, Elena de la; Valdivia Giménez, Victoria Esther; Fernández Fernández, Inmaculada; Química Orgánica y Farmacéutica; Medicina; Farmacología; Ministerio de Ciencia, Innovación y Universidades (MICIU). España
Isothiocyanates (ITCs) are well-known electrophilic agents with antioxidant and anticancer properties, largely attributed to their ability to activate the Nrf2/ARE pathway. Building on previous work with C1-ITC glycosyl derivatives, we designed and synthesized a new series of S-glycosyl isothiocyanates in which the ITC group was repositioned to the C6 carbon of the glucose scaffold. This structural rearrangement yielded stable and synthetically accessible derivatives with markedly enhanced biological profiles. Several compounds showed potent Nrf2 activation at non-cytotoxic concentrations, with CD values comparable to or exceeding those of natural ITCs. In parallel, the new C6-ITC derivatives displayed significant antiproliferative activity against leukemia and solid tumor cell lines. Among them, the phenylsulfone derivative 13 emerged as a particularly promising dual-action molecule, combining strong Nrf2 induction with low-micromolar cytotoxicity. Molecular docking was used as a hypothesis-generating approach and suggested a possible interaction with the STAT3 SH2 domain, although further studies are needed to validate this target. Overall, these results support glucose-based ITCs as a versatile platform for the development of multifunctional antioxidants with complementary anticancer properties.
Biodegradable polyacrylamide-based hydrogels with unique bactericidal and osteoinductive properties to improve the clinical success of porous titanium implants
(Elsevier, 2026-01) Martínez Muñoz, Guillermo; Castellano Pozo, Maikel; Merinero de los Santos, Manuel; Casado Jurado, David; Huertas Sánchez, Pablo; Pajuelo Domínguez, Eloísa; Miguel Rodríguez, Manuel de; Begines Ruiz, Belén; Torres Hernández, Yadir; Alcudia Cruz, Ana; Química Orgánica; Genética; Microbiología y Parasitología; Citología e Histología Normal y Patológica; Ingeniería y Ciencia de los Materiales y del Transporte; Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España
Stress-shielding phenomenon, infections, and limited bone integration are traditional drawbacks associated with titanium implants. Biodegradable polyacrylamide-based hydrogels synthesized with an 8-fold scaled up, disulfide bond-containing crosslinker, were prepared to overcome these limitations. Hydrogels' biodegradability in the presence of glutathione has been demonstrated. Additionally, hydrogels exhibited strong antibacterial activity against pathogens such as P. aeruginosa and S. aureus, along with promising osseointegrative properties, in vitro fibroblast (CCL-1) viability, and in vivo biocompatibility in C. elegans. Porous titanium (Ti) fabricated via space-holder technique were infiltrated with previously described hydrogels. The optimal system, featuring a 4 wt% crosslinked acrylamide-based hydrogel infiltrated into 60 vol%, 355–500 μm Ti substrate, showed excellent biomechanical integrity and biofunctionality, supporting its potential as a safe and effective bone implant. Additionally, the study introduces streamlined, cost-effective methodologies for implant testing and characterization.
Study of the properties of the new biodegradable polyurethane PU (TEG-HMDI) as matrix forming excipient for controlled drug delivery
(Taylor & Francis, 2013) Campiñez, María Dolores; Aguilar de Leyva, Mercedes Ángela; Ferris, Cristina; Paz Báñez, María Violante de; Galbis Pérez, Juan Antonio; Caraballo Rodríguez, Isidoro; Farmacia y Tecnología Farmacéutica; Química Orgánica y Farmacéutica
The purpose of this work is to study the ability of a new biodegradable polyurethane PU(TEG-HMDI) obtained by reaction of triethylene glycol (TEG) with 1,6-hexamethylene diisocyanate (HMDI) to act as matrix forming polymer for controlled release tablets and to estimate its percolation threshold in a matrix system. Matrix tablets weighing 250 mg were prepared by direct compression with 10–30% wt/wt of PU(TEG-HMDI) and anhydrous theophylline as model drug. Release studies were carried out using the paddle method. The results were analyzed using the kinetics models of Higuchi, Korsmeyer-Peppas, and Peppas and Sahlin. These studies confirm the existence of an excipient percolation threshold between 10 and 20 % wt/wt of PU(TEG-HMDI) for the different batches prepared. It has been observed that the new biodegradable polyurethane PU(TEG-HMDI) shows adequate compatibility as well as a high ability to control the drug release.
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, María Luisa; 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.

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