Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)

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Development and Characterization of Lyophilized Chondroitin Sulfate-Loaded Solid Lipid Nanoparticles: Encapsulation Efficiency and Stability
(MDPI, 2025-01-10) Bustos Araya, Marta Eduviges; Nardi Ricart, Anna; Calpena Campmany, Ana Cristina; Prohens López, Rafael; Miñarro Carmona, Montserrat
This study explores the development and characterization of lyophilized chondroitin sulfate (CHON)-loaded solid lipid nanoparticles (SLN) as an innovative platform for advanced drug delivery. Background/Objectives: Solid lipid nanoparticles are increasingly recognized for their biocompatibility, their ability to encapsulate diverse compounds, their capacity to enhance drug stability, their bioavailability, and their therapeutic efficacy. Methods: CHON, a naturally occurring glycosaminoglycan with anti inflammatory and regenerative properties, was integrated into SLN formulations using the hot microemulsion technique. Two formulations (SLN-1 and SLN-2) were produced and optimized by evaluating critical physicochemical properties such as particle size, zeta potential, encapsulation efficiency (EE%), and stability. The lyophilization process, with the addition of various cryoprotectants, revealed trehalose to be the most effective agent in maintaining nanoparticle integrity and functional properties. Results: Morphological analyses using transmission electron microscopy (TEM) and atomic force microscopy (AFM) confirmed the dimensions of the nanoscales and their structural uniformity. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) revealed minimal excipient interaction with CHON, ensuring formulation stability. Stability studies under different environmental conditions highlighted that SLN-2 is the most stable formulation, maintaining superior encapsulation efficiency (≥88%) and particle size consistency over time. Conclusions: These findings underscore the potential of CHON-loaded SLNs as promising candidates for targeted, sustained-release therapies in the treatment of inflammatory and degenerative diseases.
Naturally-derived cellulose-chitosan soft-hydrogel for sustained local docetaxel micelles delivery: from in silico modeling to preclinical validation in ovarian and glioblastoma models
(Elsevier, 2026-03-11) Alcina-Milà, Àngels; Rafael, Diana; Mancilla, Sandra; García Prats, Belén; Diaz-Riascos, Zamira V.; Accardo, Antonella; Ferrer Costa, Roser; Schwartz Jr, Simó; Durán-Lara, Esteban; Marto, Joana; Sureda de la Fuente, Magalí; Vitelli, Giacomoluciano; Campos-Moreno, Sofia; Dike Manica Malachy, Ogechi; German-Cortés, Júlia; José Peresson, Sergio; Goode-Romero, Guillermo; Ávila-Salas, Fabian; Fischer-Albiol, Narine; Montanarella, Vincenzo; Aguayo-Ortiz, Rodrigo; Moltó Abad, Marc; Andrade, Fernanda
Natural biopolymer-based hydrogels represent a promising strategy for localized drug delivery in cancer therapy, helping to overcome the systemic toxicity, limited specificity, and drug resistance associated with conventional treatments. However, sustained delivery of highly hydrophobic drugs using fully natural, physically crosslinked systems remains challenging. We report a fully natural, injectable cellulose-chitosan soft-hydrogel (HG) embedding docetaxel (DTX)-loaded Soluplus® micelles as a multifunctional depot for prolonged local chemotherapy. HG is formed without synthetic crosslinkers and rationally designed using in silico microspecies prediction and molecular dynamics simulations, providing insight into polymer-polymer and drug-carrier interactions, which were corroborated experimentally. Micelles with ∼72 nm diameter efficiently encapsulated DTX (>95%) and homogeneously distributed within the HG matrix. The formulation exhibited shear-thinning and thixotropic behavior, enabling injectability with forces of 30–35 N followed by in situ depot formation. The HG retained structural integrity for over 21 days, showed gradual degradation (∼50% mass loss at 28 days), and enabled sustained DTX release (∼70% over 14 days) under physiological conditions. Biological evaluation demonstrated excellent cytocompatibility in healthy fibroblasts and significant antiproliferative activity in ovarian cancer and glioblastoma models, including 3D tumor spheroids. Overall, this work introduces a sustainable, fully biopolymeric platform for localized and prolonged chemotherapy with reduced systemic toxicity.
Development of a Carprofen-Loaded Nanoemulsion for Topical Management of Post-Surgical Inflammation
(MDPI, 2026-05-25) Feroze-Bakht, Ayesha Bibi; Espinoza Tituana, Lupe Carolina; Sosa Díaz, Lilian Elisa; Zelaya, Mireia; Gualotuña Campoverde, Dagmar; Morillo-Poma, Jorge; Chaves Moreira Dos Santos, Délia; Braza Reyes, Antonio J.; Calpena Campmany, Ana Cristina; Silva Abreu, Marcelle
AbstractBackground/Objectives: Carprofen (CP) is a potent non-steroidal anti-inflammatory drug whose clinical use is limited by systemic adverse effects associated with oral administra-tion. The aim of this study was to develop and evaluate a CP-loaded nanoemulsion (CP-NE) as a topical formulation for the management of post-surgical inflammation in veteri-nary applications. Methods: CP-NE was physicochemically characterized in terms of droplet size, polydispersity index, morphology, pH, rheological behavior, spreadability, and stability. Biopharmaceutical performance was assessed through in vitro drug release and ex vivo permeation studies using porcine ear skin. Safety was evaluated using in vitro cytotoxicity assays in HaCaT keratinocytes, histological analysis of ex vivo porcine skin, and assessment of biomechanical skin parameters in mice. Finally, anti-inflammatory ef-ficacy was investigated in a murine model. Results: CP-NE showed a mean droplet size of approximately 140 nm, low polydispersity, spherical morphology, and Newtonian flow behavior with good spreadability. Stability studies confirmed the absence of significant physical destabilization and acceptable chemical stability under refrigerated and room temperature conditions. Release studies demonstrated sustained drug release, while per-meation assays revealed low systemic exposure and high drug retention within the skin. Safety evaluations indicated good biocompatibility with no cytotoxicity, no histological alterations in skin tissue, and no alteration of the skin’s biomechanical properties in vol-unteers. In vivo efficacy studies showed that CP-NE significantly reduced post-surgical inflammation, promoting faster restoration of skin architecture and improved wound ap-pearance. Conclusions: These findings suggest that CP-NE represents a promising topical delivery system for localized anti-inflammatory therapy following surgical procedures, offering significant potential for veterinary applications.Keywords: carprofen; nanoemulsion; drug delivery systems; inflammation
Synthesis and biological profiling of new 1,2,3,4-tetrahydrobenzo[h]naphthyridine-based hybrids as dual inhibitors of β-amyloid and tau aggregation with anticholinesterase activity
(MDPI, 2026-04-16) Verano Buenavidez, Aldrick; Muñoz-Torrero López-Ibarra, Diego; Sampietro, Anna; Pérez, Belén; Bartolini, Manuela; Loza, María Isabel; Galdeano Cantador, Carloss; Mallo Abreu, Ana; Brea, José; Spagnuolo, Rosaria; Sabaté Lagunas, Raimon; Juárez Jiménez, Jordi
DP-128 is a multitarget benzonaphthyridine-6-chlorotacrine hybrid molecule with potentin vitro anticholinesterase and Aβ42 and tau anti-aggregating activity. While often usedas a reference protein aggregation inhibitor, its further development as an anti-Alzheimeragent is limited by significant cytotoxicity, suboptimal aqueous solubility and microsomalstability. Since these drawbacks might arise from its rather high lipophilicity, in this workwe have developed a series of more polar analogues, designed by structural modificationsat the benzonaphthyridine or 6-chlorotacrine moieties or within the eight-atom linker.Half of the new analogues are indeed slightly more soluble and clearly less cytotoxic thanDP-128, display single-digit acetylcholinesterase inhibitory activity, and retain the Aβ42and tau anti-aggregating potency of the lead, as well as favourable brain permeation andhigh plasma stability. While further optimization of microsomal stability is necessary fora potential therapeutic use of this class of compounds, hybrids 16 and 17, with similar oreven higher Aβ42 and tau anti-aggregating activity and lower cytotoxicity than DP-128,might represent novel pharmacological tools for protein aggregation studies.
An Affordable and Simple Novel Approach to Obtain the Heat Transfer Coefficient (Kv) for Primary Drying Models Without Product Temperature Sensors
(American Association of Pharmaceutical Scientists, 2026-02-25) Amor, C. A.; Nardi Ricart, Anna; Ticó Grau, Josep R.; Samarkanova, D.; Miñarro Carmona, Montserrat
In this paper a novel method to obtain the heat transfer coefficient Kv value by the gravimetric method without using product temperature sensors is described. The sublimation front temperature is measured manometrically (indirectly by measuring the pressure). The key finding is a method to obtain the Kv value by using a primary drying model with a tailored algorithm. The authors have named it the gravi-manometric method. Kv values at different pressures are presented for two different containers: a freeze-drying stainless-steel cup, and for nested vials. The traditional gravimetric method has been compared against the new gravi-manometric method. Product temperature measurement can be challenging in applications with complex accessibility, as in large batch freeze dryers or when using protective membranes which enclose the product. This novel method is presented as an affordable and simple procedure by which the Kv value is obtained. The gravi-manometric method has the advantage that all the Kv values for a whole batch of vials can be obtained, as it is not limited to a discrete number of product temperature sensors. Keywords: freeze drying cup; heat transfer coefficient; lyophilization; manometric temperature measurement; primary drying model.
Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimers disease in metabolically stressed APPswe/PS1dE9 mice
(BioMed Central, 2021-07-22) Ettcheto Arriola, Miren; Sánchez López, E. (Elena); Cano Fernández, Amanda; Carrasco, Marina (Carrasco Pérez); Herrera, Katherine; Manzine, Patricia; Espinosa Jiménez, Triana; Busquets Figueras, Oriol; Verdaguer Cardona, Ester; Olloquequi, Jordi; Auladell i Costa, M. Carme; Folch, Jaume; Camins Espuny, Antoni
Several studies stablished a relationship between metabolic disturbances and Alzheimer´s disease (AD) where inflammation plays a pivotal role. However, mechanisms involved still remain unclear. In the present study, we aimed to evaluate central and peripheral effects of dexibuprofen (DXI) in the progression of AD in APPswe/PS1dE9 (APP/PS1) female mice, a familial AD model, fed with high fat diet (HFD). Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice, at 6 months. Moreover, mice were divided into subgroups to which were administered drinking water or water supplemented with DXI (20 mg kg-1 d-1) for 3 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-ITT) were performed to evaluate peripheral parameters and also behavioral tests to determine cognitive decline. Moreover, molecular studies such as Western blot and RT-PCR were carried out in liver to confirm metabolic effects and in hippocampus to analyze several pathways considered hallmarks in AD. Results: Our studies demonstrate that DXI improved metabolic alterations observed in transgenic animals fed with HFD in vivo, data in accordance with those obtained at molecular level. Moreover, an improvement of cognitive decline and neuroinflammation among other alterations associated with AD were observed such as beta-amyloid plaque accumulation and unfolded protein response. Conclusions: Collectively, evidence suggest that chronic administration of DXI prevents the progression of AD through the regulation of inflammation which contribute to improve hallmarks of this pathology. Thus, this compound could constitute a novel therapeutic approach in the treatment of AD in a combined therapy.
Drug Discovery Approaches to Target E3 Ligases
(Wiley-VCH, 2024-12-17) Rodríguez Gimeno, Alejandra; Galdeano Cantador, Carloss
Targeting E3 ligases is a challenging area in drug discovery. Despite the human genome encoding for more than 600 E3 ubiquitin ligases, only a handful of E3 ligases have been pharmacologically modulated or exploited for targeted protein degradation (TPD) strategies. The main obstacle for hijacking these E3 ligases is the lack of small-molecule ligands. As research into this field advances, the identification of new small molecules capable of binding to E3 ligases has become an essential pursuit. These ligases not only expand the repertoire of druggable targets but also offer the potential for increased specificity and selectivity in protein degradation. The synergy between academia and industry is key, as it combines academic expertise in fundamental research with the industrial capabilities of translating these findings into novel therapeutics. In this review, we provide an overview of the different strategies employed in academia and industry to the discovery of new E3 ligases ligands, showing them with illustrative cases.
Prescription of vitamin D in neonates and infants under one year of age in Spain: An eight-year observational study
(BioMed Central, 2026-02-25) Lizano Díez, Irene; Viñas Bastart, Montserrat; Braza Reyes, Antonio J.; Figueiredo Escribá, Carlos de; Mariño Hernández, Eduardo L.; Modamio Charles, Pilar; Jorge-Novoa, Camila; Muñoz-Cortés, Mónica
in early life. While its supplementation is widely recommended during infancy, data on prescribing patterns in the pediatric population— especially in a primary health care setting—are limited, particularly in Spain. Objective To determine the prevalence and characteristics of vitamin D prescriptions in infants under one year of age in Spain, and to identify potential safety concerns related to off-label use and excipients. Methods We conducted a cross-sectional, observational study using prescription data from January 2013 to December 2020. All prescriptions of medications containing vitamin D (cholecalciferol or calcifediol) for infants aged < 1 year in primary health care were analyzed. Variables included were pharmaceutical form, dosage regimen, age indication, prescription requirement, and the presence of mandatory-declaration excipients. Results A total of 4,829,158 prescriptions were recorded. Cholecalciferol was the most frequently prescribed active ingredient (96.43%). Considering all vitamin D medications, oral solution was the predominant pharmaceutical form (99.43%), and daily administration was the most common dosing regimen (96.51%). Off-label prescriptions accounted for 4.03% of the total, often involving adult-only formulations or pharmaceutical forms unsuitable for infants, such as tablets/capsules and orodispersible tablets. Several medications included excipients with known pediatric safety concerns, such as ethanol, sorbitol, aspartame, and sucrose. Conclusion This large long-term study provides critical insight into vitamin D prescribing practices in primary care for infants in Spain. While most prescriptions aligned with pediatric recommendations, the presence of off-label use and potentially harmful excipients highlights the need for improved regulatory oversight and prescriber awareness. Highlights • Analysis of 4.8 million vitamin D prescriptions in Spanish neonates and infants aged < 1 year. • 96.43% of prescriptions involved cholecalciferol, primarily as an oral solution with daily dosing.
Reaction space charting as a tool in organic chemistry research and development
(Wiley-VCH, 2024-01-31) Lozano Baró, Eloy; Nadal Rodríguez, Pau; Juárez-Jiménez, Jordi; Ghashghaei, Ouldouz; Lavilla Grífols, Rodolfo
The chemical and reaction spaces are incredibly vast and special procedures are required tostudy them. Their complex and multiparametric nature encompass myriads of compounds and inter-actions and endless modifications involving the distinct impact of relevant variables (temperature, solvent, stoichiometry, etc.). This often calls for the design, collection, and analysis/interpretation of large datasets. Reaction charting, the systematic scanning,description, analysis, and guided modifications of a given process, stands as the most promising approach. It offers fast and accurate solutions as well as expanding the knowledge about the systems. This deeper understanding enables reliable predictions, improvement of the productivity (yields, scope),eventually leading to sustainable, economic, and safe applications. The present review introduces the topic, analyzing selected examples and recent advancements in different organic chemistry-related fields. The covered methodologies range from classical experimentation modifying one factor at a time, to Design of Experiments and more modern computational approaches involving Machine Learning and Artificial Intelligence. In this way, the impact of charting in process development, biological and medicinal chemistry, catalysis, reaction discovery and computational methods is accounted. Finally, the conclusion/outlook section gives a general appraisal and a prospect on the future implementation of the methodology.
Exploration of moisture activated dry granulation for the development of gastroretentive tablets aided by SeDeM diagram
(Elsevier B.V., 2024-10-01) Nardi Ricart, Anna; Suñé Pou, Marc; Pérez Lozano, Pilar; Romero Obon, Miquel; Suñé i Negre, Josep M. (Josep Maria); Ochoa-Andrade, Ana Teresa; García Montoya, Encarna
Moisture activated dry granulation (MADG) is an attractive granulation process. However, only a few works have explored modified drug release achieved by MADG, and to the best of the authors knowledge, none of them have explored gastroretention. The aim of this study was to explore the applicability of MADG process for developing gastroretentive placebo tablets, aided by SeDeM diagram. Floating and swelling capacities have been identified as critical quality attributes (CQAs). After a formulation screening step, the type and concentration of floating matrix formers and of binders were identified as the most relevant critical material attributes (CMAs) to investigate in ten formulations. A multiple linear regression analysis (MLRA) was applied against the factors that were varied to find the design space. An optimized product based on principal component analysis (PCA) results and MLRA was prepared and characterized. The granulate was also assessed by SeDeM. In conclusion, granulates lead to floating tablets with short floating lag time (<2 min), long floating duration (>4 h), and showing good swelling characteristics. The results obtained so far are promising enough to consider MADG as an advantageous granulation method to obtain gastroretentive tablets or even other controlled delivery systems requiring a relatively high content of absorbent materials in their composition
The piper at the gates of brain: A systematic review of surface modification strategies on lipid nanoparticles to overcome the Blood-Brain-Barrier
(Elsevier B.V., 2024-09-13) Vargas, Ronny; Suñé Pou, Marc; Lizano-Barrantes, Catalina; Romero Obon, Miquel ; València Clua, Kevin; Narváez-Narváez, David; Suñé i Negre, Josep M. (Josep Maria); Pérez Lozano, Pilar; García Montoya, Encarna; Martinez-Martinez, Noelia; Hernández-Munain, Cristina; Suñé, Carlos
The Blood-Brain Barrier (BBB) significantly impedes drug delivery to the central nervous system. Nanotechnology, especially surface-functionalized lipid nanoparticles, offers innovative approaches to overcome this barrier. However, choosing an effective functionalization strategy is challenging due to the lack of detailed comparative analysis in current literature. Our systematic review examined various functionalization strategies and their impact on BBB permeability from 2041 identified articles, of which 80 were included for data extraction. Peptides were the most common modification (18) followed by mixed strategies (12) proteins (9), antibodies (7), and other strategies (8). Interestingly, 26 studies showed BBB penetration with unmodified or modified nanoparticles using commonly applied strategies such as PEGylation or surfactant addition. Statistical analysis across 42 studies showed correlation between higher in vivo permeation improvements and nanoparticle type, size, and functionalization category. The highest ratios were found for nanostructured lipid carriers or biomimetic systems, in studies with particle sizes under 150 nm, and in those applying mixed functionalization strategies. The interstudy heterogeneity we observed highlights the importance of adopting standardized evaluation protocols to enhance comparability. Our systematic review aims to provide a comparative insight and identify future research directions in the development of more effective lipid nanoparticle systems for drug delivery to the brain to help improve the treatment of neurological and psychiatric disorders and brain tumours.
Allosteric rescue of catalytically impaired ATP phosphoribosyltransferase variants links protein dynamics to active-site electrostatic preorganisation
(Nature Publishing Group, 2022-12) Fisher, G.emma; Corbella i Cordomí, Montserrat; Alphey, Magnus S.; Nicholson, John; Read, Benjamin J.; Kamerlin, Shina Caroline Lynn; Da Silva, Rafael G.
ATP phosphoribosyltransferase, which catalyzes the first step of histidine biosynthesis, is regulated by a complex allosteric mechanism involving the regulatory protein HisZ and the catalytic subunit HisGS. HisZ enhances catalysis and mediates inhibition by histidine, even though it binds about 20 Å away from the active site.The study shows that mutations in key active-site residues of HisGS that impair catalysis can be functionally rescued by HisZ. Molecular dynamics simulations reveal that HisZ binding restricts HisGS dynamics, promoting a preorganized active site in which Arg56 and Arg32 stabilize the departure of the pyrophosphate leaving group. In the Arg56Ala mutant, HisZ shifts Arg32 dynamics to partially compensate for the missing Arg56.Overall, the work demonstrates how long-range protein–protein interactions can restore catalytic activity by reestablishing electrostatic preorganization at the active site, highlighting a mechanism for allosteric rescue and catalytic resilience.
Supramolecular gels for antimicrobial photodynamic therapy against E. coli and S. aureus
(Elsevier, 2025-04-01) Anguluri, Kavya; Sharma, Bunty; Bagherpour, Saman; Calpena Campmany, Ana Cristina; Halbaut, Lyda; Amabilino, David B.; Kaur, Gurpreet; Chaudhary, Ganga Ram; Pérez García, M. Lluïsa (Maria Lluïsa)
Singlet oxygen (SO) reacts with organic molecules, for example in degrading environmental contaminants and causing toxicity to cells in photodynamic therapy (PDT). The relevance of SO in the environmental and biomedical domains has fuelled research towards improved methodologies for its efficient generation. In this paper, we report the use of a bis-imidazolium-based amphiphile that forms supramolecular gels in water-ethanol mixtures encapsulating SO generating chromophores. The gels comprise twisted fibres that incorporate one of four different porphyrins: 5,10,15,20-tetrakis(N-methyl-4-pyridinium)porphyrin tetraiodide (TPPP), 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP), 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (TPP-3OH) and 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin (TPP-4OH). Rheological measurements confirmed viscoelastic properties characteristic of these types of supramolecular gels, suggesting their potential as effective local PDT delivery systems. Enhanced SO generation within the hydrogel matrix compared to the solution of the chromophores was observed in suspension in a spectrophotometer using uric acid as the molecular probe. The SO generation was also shown through antimicrobial PDT (aPDT) studies. The TPPP-containing gel showed the highest reduction in the colony forming unit (CFU) count, which is 94% against E. coli and 100% against S. aureus. These results indicate that the porphyrin gels based on a gemini amphiphile with a high level of SO production are of significant interest and have a lot of potential use in aPDT.
Nanostructured lipid carriers co-encapsulating Apigenin and Melatonin: An innovative strategy against cancer
(Elsevier, 2025-02-01) Bonilla Vidal, Lorena; Switalska, Marta; Espina García, Marta; Wietrzyk, Joanna; García López, María Luisa; Souto, Eliana B.; Gliszczyńska, Anna; Sánchez-López, E. (Elena)
Cancer remains a global health concern, being one of the leading causes of premature death worldwide. In 2020, around 19 million people were diagnosed with cancer, leading to approximately 10 million deaths [1], [2]. Conventional cancer therapies, including chemotherapy and radiotherapy, often exhibit adverse effects and suboptimal treatment outcomes. Specifically, chemotherapy is frequently administered to over 50 % of cancer patients, but it can simultaneously impact both healthy and cancerous cells, causing significant side effects. Moreover, these therapies can induce chemoresistance, compromising their effectiveness over time [3], [4]. As a result, there is an urgent need for the development of innovative therapeutic strategies to address these limitations.
A Thermosensitive Gel Containing Biodegradable Nanoparticles Carrying Calcium Hydroxide as Antibacterial Intracanal Therapy
(John Wiley & Sons, 2025-12-01) Duran-Sindreu, Fernando; Roig-Soriano, Xavier; Delgado, Luís María; Elmsmari, Firas; Teulé Trull, Míriam; Espina García, Marta; Esteruelas Navarro, Gerard; García López, María Luisa; González Sánchez, Jose Antonio; Sánchez-López, E. (Elena)
Aim: To characterise and evaluate mucoadhesive strength and antibacterial properties of a nanotechnological formulation forendodontic disinfection based on biodegradable nanoparticles dispersed in a thermosensitive gel containing calcium hydroxide(Ca(OH) 2 -NPs-gel).Methodology: Morphology of Ca(OH) 2 -NPs-gel was studied using transmission electron microscopy. Moreover, Ca(OH) 2 -NPs-gel was sterilised using gamma irradiation (25 kGy), and the stability after the sterilisation process was studied by measuringCa(OH) 2 -NPs-gel average size, polydispersity index, zeta potential and encapsulation efficiency. To assess the ex vivo mucoad-hesive strength, extracted single-rooted human teeth were used to measure the force necessary to separate the formulationfrom the teeth. In addition, the short-time stability of Ca(OH) 2 -NPs-gel was evaluated monthly, analysing entrapment efficacy,backscattering and transmittance of Ca(OH) 2 -NPs-gel stored at different temperatures (4°C, 25°C and 37°C). Furthermore, theantibacterial analysis of Ca(OH) 2 -NPs-gel was performed against Enterococcus faecalis inoculated in extracted human single-root teeth and evaluated by confocal and scanning electron microscopy. Finally, the metabolic activity of bacteria was studiedthrough a resazurin assay to evaluate bacterial survival after treatment.Results: Ca(OH) 2 -NPs-gel owned a round shape and a smooth surface without particle aggregation. Sterilisation did not inducean alteration in Ca(OH) 2 -NPs-gel physicochemical properties and Ca(OH) 2 -NPs-gel presented a high adhesion strength. In addi-tion, 4°C was the best temperature to store Ca(OH) 2 -NPs-gel. Regarding the antibacterial therapeutic efficacy, Ca(OH) 2 -NPs-gelpossesses suitable antibacterial properties, indicating that it efficiently reduces bacterial biofilms.Conclusion: Calcium hydroxide-loaded PLGA nanoparticles dispersed in a thermosensitive gel have been developed, optimisedand characterised, obtaining excellent antibacterial properties and achieving bacterial disinfection levels similar to those ofcommercial formulations.
Unraveling Charge-Transfer States and Their Ultrafast Dynamics in Artificial Light-Harvesting Complexes
(American Chemical Society, 2026-01-11) Teixeira Alves Duarte, Luís Gustavo; Lamas, Iker; Bäuerle, Dominik; Shareef, Saeed; Cunha, Renato D.; Curutchet Barat, Carles E.; Curti, Mariano; Romero, Elisabet
Photosynthesis relies on highly organized pigment–protein complexes in order to store sunlight energy as biochemical energy. These complexes capture light with remarkable efficiency and are responsible for ultrafast charge separation within a finely tuned energy landscape provided by the protein environments, producing one of nature’s most sophisticated energy conversion systems. Inspired by nature, de novo designed proteins have been proven to be versatile platforms to emulate the function of natural light-harvesting complexes and reaction centers. With Stark and ultrafast transient absorption spectroscopies, we explored the exciton and charge-transfer (CT) mixing, as well as the excited-state dynamics, of a chlorophyll a analogue (Zn-pheophorbide a) in dimers formed within 4-α-helix bundles whose design was previously guided by molecular dynamics simulations. Due to dimerization, we observe an increase in the CT character of the excitonically coupled dimers’ excited state in comparison to monomeric ZnP. Furthermore, additional nonradiative relaxation pathways, together with the formation of transient species absent in monomeric systems, were observed for the dimers. We demonstrate that de novo designed proteins can replicate key features of photosynthetic energy conversion, serving as tunable scaffolds for optimizing light-harvesting processes. Ultimately, these systems have promising applications including photovoltaic cells and biomedical treatments based on sustainable materials.
Uso fuera de indicación de la combinación a dosis fija de tramadol/dexketoprofeno en atención primaria de salud: ¿Basado en la evidencia científica o motivo de preocupación?
(Fundación Pharmaceutical Care, 2022) Viñas Bastart, Montserrat; Oms, Míriam; Pedraza-Gutiérrez, Àfrica; Lizano Díez, Irene; Mariño Hernández, Eduardo L.; Modamio Charles, Pilar
La utilización de la combinación a dosis fija de tramadol/dexketoprofeno en España y en otros países ha aumentado de forma considerable. La indicación terapéutica autorizada de este medicamento es el tratamiento sintomático a corto plazo del dolor agudo de moderado a intenso en pacientes adultos. El objetivo de este estudio fue describir el patrón de uso de tramadol/dexketoprofeno en el ámbito de la atención primaria de salud.Método: Se realizó un estudio transversal, descriptivo y multicéntrico. La población de estudio incluyó a todos los pacientes de una Dirección de Atención Primaria (53 equipos de Atención Primaria) que tenían activa la prescripción de tramadol/dexketoprofeno el 28 de marzo de 2018. La población diana fueron aquellos pacientes a los que se les prescribió tramadol/dexketoprofeno durante más de 20 días.Resultados: Un total de 176 pacientes tenía activa la prescripción de tramadol/dexketoprofeno. Todos los pacientes (100%) tuvieron una duración del tratamiento superior a 5 días y el 72,7% (N=128) superior a 20 días. La duración media del tratamiento fue de 14±160,9 días en pacientes que tenían menos de 20 días de tratamiento y de 224±160,8 días en pacientes que tenían más de 20 días de tratamiento. El 35,1% de los pacientes estaban tratados con más de 2 medicamentos para aliviar el dolor de forma concomitante con tramadol/dexketoprofeno. El médico de atención primaria inició un 65,6% de las prescripciones.Conclusiones: La combinación a dosis fija de tramadol/dexketoprofeno se utilizó con frecuencia fuera de indicación, de acuerdo con la ficha técnica y la evidencia científica disponible. Este estudio alerta sobre los riesgos potenciales asociados a la utilización de este medicamento en la práctica clínica, como son la falta de efectividad y/o la aparición de efectos adversos.
Diseño y validación de 2 instrumentos para analizar y evaluar la calidad formal en el proceso de consentimiento informado de ensayos clínicos con medicamentos
(Sociedad Española de Farmacia Hospitalaria, 2023) Jaramillo Velez, A. G.; Aguas Compaired, M. (Margarita); Granados Plaza, M.; Mariño Hernández, Eduardo L.; Modamio Charles, Pilar
Objetivo: la actividad de los promotores y Comitésde ÉticadelaInvestigación con medicamentos haaumentado enlosúltimosaños.Elobjetivofuediseñaryvalidar2instrumentosparaanalizaryevaluarlacalidadformal dela hoja de información al participante y el formulario de consentimiento informado de ensayos clínicos con medicamentos, acorde con la legislación. Método: diseño (Buenas Prácticas Clínicas y normativas europea y española); validación (método Delphi y consenso de expertos: concordancia ≥ 80%); fiabilidad (método inter-observadores, índice Kappa). 40 hojas de información al participante/consentimientos informados evaluados. Resultados: se obtuvo muy buena concordancia en ambos instrumentos (k ≥ 0,81, p b 0,001). Las versiones definitivas estaban formadas por: checklist-hoja de información al participante: 5 secciones, 16 ítems y 46 subítems; checklist-consentimiento informado: 11 ítems. Conclusiones: los instrumentos desarrollados son válidos, fiables y facilitan el análisis, la evaluación y la toma de decisión sobre las hojas de información al participante/consentimientos informados de ensayos clínicos con medicamentos.
A study protocol for an experimental study for a pharmaceutical care programme to improve chronic complex disease management: PCAF programme
(Open Access Text, 2021) Torres-Novellas, Berta; Guayta, Rafael (Guayta Escolies); Rius, Pilar; Castellà, Amparo; Gascón Lecha, M. Pilar; Modamio Charles, Pilar; Mariño Hernández, Eduardo L.
The prevalence of elderly patients with chronic illnesses, associated polypharmacy and a high risk of functional and cognitive impairment has increased in recentyears. The care of Complex Chronic Patients (CCP) therefore represents a challenge for health systems in developed countries around the world. This paper presentsa study protocol that will explore the effects of an intervention within a pharmaceutical care programme (PCAF) on optimising CCP care and on the suitability ofthe organisational methods proposed for the PCAF programme.This is a multicentre experimental study. The setting will be primary health care and community pharmacies in the so-called ‘autonomous community’ of Cataloniain Spain. The participants will be CPP attended to Primary Healthcare Centres with the CCP code in their electronic medical record. The included CCP will bedistributed in two strata depending on whether they will be considered likely to receive the arranged medicinal treatment as Monitored Dosage System accordingto benefits based on criteria or not. They will then be assigned by random stratified sampling at a ratio of 1:1 to the control or intervention groups. A sample size of860 patients is estimated. Patients will undergo 12 months follow-up. The primary outcome of this study will be the medication adherence measured by the MoriskyGreen Test and the billing/prescription ratio.
Assessment of the quality of patient information sheets and informed consent forms for clinical trials at a hospital neurology service
(Wiley, 2020-07-20) Jaramillo Velez, A. G.; Aguas Compaired, M. (Margarita); Granados Plaza, M.; Mariño Hernández, Eduardo L.; Modamio Charles, Pilar
Background and purpose: Clinical trials (CTs) aimed at vulnerable groups, such as patients with mental disorders, create ethical complexity. The patient information sheet (PIS) should provide all of the information about the CT that is relevant to the subject's decision to participate. After being informed, the subject will decide freely whether to take part in the CT and will read and sign the informed consent form (ICF). The objective was to assess the quality of PISs/ICFs from a hospital neurology service. The assessment was made using validated and reliable checklists of the information included in the PISs/ICFs of CTs with medicinal products.Methods: The study comprised analyses of compliance with the checklists of 21 PISs and ICFs reviewed/approved during 2016-2017 by a medicinal research ethics committee.Results: All PISs/ICFs were from multicenter CTs sponsored by pharmaceutical companies in different therapeutic areas, mainly Parkinson's (52.4%) and Alzheimer's (38.1%) diseases. The PISs from the neurology service demonstrated good compliance (≥80%) with the checklist, whereas ICFs should be improved. Sponsors omitted some relevant information, such as the study title or that the participant be informed of any information arising from the research that may be relevant to the subject's health, although this information may be in the PIS.Conclusions: The PISs/ICFs of CTs of medicinal products that are currently used need improvement. PISs and ICFs should be separate documents for each CT. In particular, the PISs/ICFs should consider the criteria related to the decision of participants, protect their rights and ensure that the information received is complete.

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