Artículos (Farmacia y Tecnología Farmacéutica)

URI permanente para esta colecciónhttps://hdl.handle.net/11441/11020

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Subretinal Transplant of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium on Nanostructured Fibrin-Agarose
(SAGE Publications, 2019-11-04) García Delgado, Ana Belén; De la Cerda, Berta; Alba Amador, Julia; Valdés Sánchez, Maria Lourdes; Fernández Muñoz, Beatriz; Relimpio López, Isabel; Rodríguez de la Rúa Franch, Enrique; Díaz Corrales, Francisco J.; Farmacia y Tecnología Farmacéutica; Cirugía; Junta de Andalucía; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER)
Damage to the retinal pigment epithelium (RPE) in age‐related macular degeneration (AMD) and other diseases results in photoreceptor cell death and blindness. Replacement of RPE is therefore being explored as a therapy for several retinal diseases. To move towards a future personalized autologous transplant approach, we have prepared a biocompatible implant using RPE derived from induced pluripotent stem cells (iPSC) reprogrammed from a healthy donor´s monocytes. The correct positioning of the polarized RPE is essential to fulfill its role and protect photoreceptors from degeneration. Hence, we have used a biocompatible hydrogel matrix of fibrin and agarose (FAH) that allows the surgical placement of an RPE sheet in the subretinal space, keeping its functional orientation. Our aim was to demonstrate safety and viability of the transplant in preclinical models. Pigs were used to test the feasibility of a regular vitreo‐retinal surgery. Our results show that this implant is suitable for subretinal transplantation allowing human RPE cells to survive and maintain their phenotype and orientation without any local or systemic adverse events. The ability to transplant the iPSC‐derived RPE sheet in its natural orientation will surely increase the chance to obtain a therapeutic effect in future translational studies.
Systematic evaluation of subgroup analyses of inhaled treprostinil in pulmonary hypertension due to interstitial lung disease
(Public Library of Science (PLoS), 2025-02-12) Martínez Puig, Pablo; Báez Gutiérrez, Nerea; Rodríguez Ramallo, Héctor; Abdel-Kader Martín, Laila; Otero Candelera, Remedios; Farmacia y Tecnología Farmacéutica; Medicina
Background The INCREASE trial introduced a novel therapeutic option for Pulmonary Hypertension caused by Interstitial Lung Disease. Subsequently to this trial, several subgroup analyses were conducted, aiming to explore specific effects within subgroups. Objective This study aimed to evaluate the subgroup analyses performed in the INCREASE trial and to identify potentially reliable subgroup effects. Methods A methodological assessment of the subgroup analyses was performed. Claims of subgroup effect were evaluated using three different tools: Sun, X et al. 2012, Gil-Sierra, M.D et al2020, and Schandelmaier, S et al. 2020. Additionally, all statistically significant subgroup effects that were not claimed by the authors were evaluated. Results Five claims of subgroup effect were identified; none of them achieved statistical significance when assessed using an interaction test. The evaluation conducted with the three tools consistently yielded very low credibility for all the claims. During the assessment, a statistically significant subgroup effect of moderate credibility was identified, which the authors did not claim: iTre appeared to improve exercise capacity exclusively in patients with Pulmonary Vascular Resistance ⋝ 4 WUs. Conclusions Due to methodological limitations, the credibility of subgroup claims from the authors of the INCREASE was lacking and, therefore, should not be relied upon to inform decisions on an individual basis.
Generation of the human iPSC line ESi148-A from a patient with sporadic amyotrophic lateral sclerosis
(Elsevier, 2026) Garcia-Delgado, A.B.; Bega, S.; Campos-Cuerva, R.; Martín-Banderas, L.; Paradas, C.; Fernández Muñoz, Beatriz; Farmacia y Tecnología Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. España; Instituto de Salud Carlos III
Nearly 90% of patients with amyotrophic lateral sclerosis (ALS) do not carry mutations in genes previously associated with the disease and are classified as sporadic cases with no identified genetic cause. In this study, peripheral blood mononuclear cells from a patient with sporadic ALS were reprogrammed to generate the human induced pluripotent stem cell (iPSC) line ESi148-A. The line was thoroughly characterized for pluripotency and genomic stability. These cells provide a valuable resource for generating 3D biomodels, such as cortical or spinal cord organoids, to investigate disease mechanisms and develop novel therapeutic approaches for sporadic ALS.
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.
Implantable and injectable drug delivery systems for pain management
(Taylor and Francis, 2025-09-02) Lu, Y. J.; Essadki Aittaji, Ilyas; Gao, J. Q.; Abraham, A. M.; Anjani, Q. K.; Cobo González, A. B.; Iglesias-Martín, Fernando; Vora, L. K.; Millán Jiménez, Mónica; Larrañeta, Eneko; Domínguez Robles, Juan; Farmacia y Tecnología Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. España
Introduction: Pain is a widespread global health issue, significantly affecting quality of life and contributing to disability. It is estimated that between 20% and 30% of the global population suffer from some form of non-cancer chronic pain. Around 80% of surgical patients report postoperative acute pain, with less than 50% achieving adequate pain control. Despite these statistics, the management of pain still remains a significant challenge for clinicians, with many patients experiencing poorly controlled pain or adverse effects related to analgesic medication. Areas covered: This literature review outlines current pain management strategies, focusing on non-oral postoperative pain therapies, including injectable drug delivery systems (such as in situ forming implants, micro- and nano-based formulations) and implantable drug delivery systems. Emphasis is placed on solid implantable devices designed for sustained drug delivery, which can offer more efficient localized drug delivery at the pain site. Expert opinion: While pharmacological treatments, including oral opioids and nonsteroidal anti-inflammatory drugs, are commonly used, implantable controlled release systems are emerging as more effective alternatives. These systems provide localized pain relief with reduced systemic exposure, minimizing side effects, opioid use, and the risk of addiction, offering a promising solution for improved postoperative pain management.
La participación de farmacéuticos y médicos cubanos en las guerras de independencia de Cuba contra España
(Universidad de Sevilla, 2025-12-30) Nuñez Valdés, Juan; Ruiz Altaba, Rocío; Moreno Toral, Esteban; Ramos Carrillo, Antonio; Geometría y Topología; Farmacia y Tecnología Farmacéutica
Este artículo demuestra la participación activa de médicos y farmacéuticos cubanos en las tres guerras de independencia contra España. Se destacan las contribuciones de la familia Figueroa Marty y de Mercedes Sirvén Pérez-Puelles. La investigación se basa en fuentes primarias consultadas en archivos oficiales cubanos y españoles. Los resultados evidencian su papel sanitario y patriótico en la causa independentista.
Long-acting drug delivery systems: Current landscape and future prospects
(Elsevier, 2025-09) Larrañeta, Eneko; Domínguez Robles, Juan; Farmacia y Tecnología Farmacéutica; Academy of Medical Sciences; Ministerio de Ciencia, Innovación y Universidades (MICIU). España
Conventional drug delivery often leads to fluctuating drug levels and reduced efficacy, especially in chronic conditions requiring sustained treatment. Long-acting drug delivery systems (LADDS) offer controlled, extended release, improving efficacy, safety, and patient adherence. This mini review outlines current injectable and implantable LADDS, including approved formulations like nanosuspensions, PLGA microspheres, oil-based injections, in situ-forming and preformed implants. Future directions explore thermoresponsive gels, polymer-drug conjugates, prodrugs, 3D printing, and reservoir-type implants using semipermeable membranes. These innovations highlight the need for continued multidisciplinary collaboration to advance next-generation long-acting therapies.
Formulation and evaluation of PVA-based composite hydrogels: physicochemical, leachables, and in vitro immunogenicity studies
(Royal Society of Chemistry, 2025-06-06) Himawan, Achmad; Korelidou, Anna; Pérez-Moreno, Ana M.; Paris, Juan L.; Domínguez Robles, Juan; Vora, Lalitkumar K.; Permana, Andi Dian; Larraneta, Eneko; Graham, Robert; Scott, Christopher J.; Donnelly, Ryan F.; Farmacia y Tecnología Farmacéutica; European Union (UE); Ministerio de Ciencia e Innovación (MICIN). España
This study explores the formulation and characterization of poly(vinyl alcohol) (PVA)-based composite hydrogels synthesized through solid-state crosslinking. Comprehensive assessments were conducted on their physicochemical properties, leachables, and immunogenicity. Swelling experiments demonstrated that the incorporation of poly(vinylpyrrolidone) (PVP) enhanced water retention, while chitosan had a minimal effect on swelling behavior. Qualitative analysis of leachables identified water-soluble components, including dehydrated PVA and PVP. Fourier-transform infrared (FTIR) spectroscopy confirmed the formation of ester bonds and indicated increased hydrogen bonding post-crosslinking. Thermal stability was validated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), with decomposition observed at 320–330 °C. X-ray diffraction (XRD) analysis revealed enhanced crystallinity following crosslinking. Solid-state nuclear magnetic resonance (NMR) further confirmed chemical changes consistent with the results from other characterization techniques. In vitro assays using DC2.4 mouse dendritic cells showed that hydrogel extracts inhibited cell proliferation without causing cytotoxicity or triggering significant immune responses. These findings highlight the hydrogels’ biocompatibility and stability, supporting their potential for biomedical applications.
Formulation and evaluation of 3D-printed dressings loaded with curcumin and levofloxacin for wound healing application
(Elsevier, 2025-11-07) Wongso, Brilivia Joan; Hartrianti, Pietradewi; Adhami, Masoud; Febriani, Erlina; Chandra, Cynthia Valentina; Anginan, Theresia Brigita Rangga Allo; Salim, Enrica Angelina; Domínguez Robles, Juan; Donnelly, Ryan F.; Larrañeta, Eneko; Anjani, Qonita Kurnia; Farmacia y Tecnología Farmacéutica; Wellcome Trust
Curcumin (CUR), traditionally used for wound healing, is a promising candidate for incorporation into wound dressings. To enhance its antibacterial efficacy, levofloxacin (LEVO), a broad-spectrum antibiotic effective against both gram-positive and gram-negative bacteria, was co-formulated. CUR and LEVO were incorporated into wound dressings using a semi-solid extrusion (SSE) 3D printing technique. The SSE approach minimised potential drug interactions and eliminated the use of organic solvents. Two different polymers, ethyl cellulose (ethocel) and corn protein (zein), were employed as the matrix materials and comparatively evaluated. The physicochemical and mechanical properties of the printed dressings were assessed, along with drug release profile and antimicrobial activity. Ethocel-based wound dressings demonstrated lower elasticity but higher fracture resistance due to superior tensile strength. In vitro release studies showed that the type of polymer (ethocel or zein) did not significantly affect the release profiles of CUR or LEVO. Antimicrobial assays revealed bacterial counts of <1 CFU/mL in all treated groups for ethocel-based wound dressing except the blank, confirming the antibacterial effectiveness of CUR, LEVO, and their combination against Staphylococcus aureus. The ethocel-CUR-LEVO group showed the most favourable wound healing response, characterised by increased epithelialisation, enhanced fibroblast migration, and reduced neovascularisation. These findings suggest that the CUR-LEVO-loaded ethocel-based dressing is a promising candidate for advanced wound care application.
Rewritting the history of spanish pharmacy in feminism
(Universidad Complutense de Madrid, 2025) Ramos Carrillo, Antonio; Nuñez Valdés, Juan; Moreno Toral, Esteban; Ruiz Altaba, Rocío; Farmacia y Tecnología Farmacéutica; Geometría y Topología
Introduction and Objectives. The main objective of this article is to highlight the role of first Spanish women in pharmacy, through history in feminine. Concretely, authors wish to praise the figure of the first Spanish female pharmaceutical university students, emphasizing the difficulties they had to overcome simply because they were women, to achieve their goals. Methodology. To publicize the history of the pioneering Spanish women of pharmacy, authors made a video which was aimed at second-year students of the degree in Pharmacy at the University of Seville (Spain) and it was elaborated according to the conditions of that time (places and clothing, above all), which was projected in a classroom of the Faculty of Pharmacy of that university and reflected, in the form of interviews, the lives of four first Spanish pharmacists, chosen from among those women who can be considered pioneers of the Spanish pharmaceutical profession, who managed to study in the first Pharmacy faculties in the country. Subsequently, students were asked to respond to a questionnaire in which they could express their impressions about the difficult life that these women had had due to issues of their gender. The enormous efforts they had to make to be able to overcome these difficulties and be able to practice their professions. Results. Apart from promoting a methodological resource that can be used by other professors in their own universities, a qualitative and quantitative statistical analysis is carried out on the responses given by the students to the aforementioned questionnaire. Conclusions and discussion. This study concludes that the pioneering women of Spanish Pharmacy laid. the first stone to try to achieve, on the one hand, equality between genders. On the other hand, to serve as references and models for those women of the future who also want to follow in their footsteps.
Microneedles From Shape-Preserving Crosslinked Poly(Vinyl Alcohol) Hydrogels: Minimising Interference in Transdermal Proteomics
(Wiley, 2025-08-22) Himawan, Achmad; Graham, Robert; Volpe-Zanutto, Fabiana; Li, Huanhuan; Pandya, Anjali K.; Aisyah, Andi Nur; Domínguez Robles, Juan; Donnelly, Ryan F.; Farmacia y Tecnología Farmacéutica; Queen's University de Belfast; European Union (UE). H2020; Ministerio de Ciencia, Innovación y Universidades (MICIU). España
Hydrogel-forming microneedle array patches (HFMAPs) enable minimally invasive interstitial fluid (ISF) sampling for biomarker detection. However, optimising their formulation to enhance biomarker recovery and minimise analytical interference while maintaining mechanical properties remains a challenge. This study presents interference-free HFMAPs fabricated from shape-preserving polyvinyl alcohol and polyvinyl pyrrolidone (PVA-PVP) hydrogel. Two formulations are developed with PVA-PVP without chitosan (PP) and with chitosan (PPChi) using micromoulding and evaluated for mechanical strength, insertion efficiency, ISF absorption, and biomarker recovery. The impact of washing to remove interference and chitosan modification on IgG sampling is assessed ex vivo, while in vivo studies measure ISF uptake and skin response. Both formulations exhibit sufficient mechanical strength for insertion, with washed patches maintaining tip sharpness despite minor shrinkage. Formulated HFMAPs absorb over 5 µL of ISF and facilitate quantifiable IgG detection ex vivo, whereas chitosan-modified patches reduce IgG recovery due to biomarker-hydrogel interactions. In vivo, all formulations absorb over 1.5 µL of ISF within 2 h, obtaining sufficient samples for subsequent analysis. Proteomic study reveale 50 to 200 proteins, with chitosan affecting abundance but not the total number detected. These findings support HFMAPs as a promising tool for non-invasive transdermal sampling of protein biomarkers, enabling subsequent proteomic analysis.
Oleocanthal Supplemented Diet Improves Renal Damage And Endothelial Dysfunction In Pristane-Induced Systemic Lupus Erythematosus In Mice
(Elsevier, 2023) Montoya García, Tatiana; Sánchez Hidalgo, Marina; Castejón Martínez, María Luisa; Vázquez Román, María Victoria; Álvarez de Sotomayor Paz, María; Ortega Vidal, Juan; González Rodríguez, María Luisa; Alarcón de la Lastra Romero, Catalina; Farmacología; Citología e Histología Normal y Patológica; Farmacia y Tecnología Farmacéutica; Ministerio de Economía y Competitividad (MINECO). España; Junta de Andalucía
Systemic lupus erythematosus (SLE) is a multiorgan disorder with a deregulated immune-inflammatory response. Nutritional therapy has been considered a promising approach to SLE management. Oleocanthal (OLE), the main extra virgin olive oil (EVOO)-derived secoiridoid, has shown to regulate the immune-inflammatory response in various disease contexts; however, its possible beneficial effects on SLE remain unclear. This study sought to evaluate the effects of OLE enriched diet on renal damage and aortic endothelial dysfunction in murine pristane-induced SLE, focusing on the action mechanisms and signaling pathways involved. BALB/c mice were injected with pristane and fed with OLE supplemented diet (0.01 % (w/w)) for six months. Levels of cytokines were measured by ELISA in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and splenocytes. Presence of IgG and IgM immune complexes was examined by immunofluorescence and immunohistochemistry. Thoracic aortas were used to evaluate endothelial dysfunction. Western blotting was employed to detect signaling pathways and oxidative-inflammatory-related mediators. Dietary OLE supplementation reduced Th1/Th17 pro-inflammatory cytokines production and alleviated renal damage by decreasing immunoglobulin complexes deposition, and inflammation-mediating enzymes expression. The mechanisms underlying these protective effects could be related to the regulation of nuclear factor erythroid 2-related factor 2/Haem oxygenase 1 (Nrf-2/HO-1), mitogen-activated protein kinases (MAPKs), signal transducer and transcription activator of transcription (STAT-3), inflammasome and, nuclear factor kappa B (NF-B) signaling pathways. Also, dietary OLE improved aortic endothelial dysfunction and vascular reactivity, normalizing endothelial nitric oxide synthase (eNOS) uncoupling, and NADPH oxidase-1 (NOX-1) overexpression. This study shows the immunomodulatory effects of OLE in an in vivo model of SLE by improving renal damage and regulating aortic endothelial dysfunction. These preliminary results provide OLE as a new therapeutic strategy in SLE management.
A Web-Based Virtual Laboratory for Teaching Chemical Synthesis: A Case Study on Lidocaine Synthesis
(American Chemical Society (ACS) Publications, 2025-07-08) Larrañeta, Eneko; McCrudden, Maelíosa T.C.; Courtenay, Aaron J.; Kearney, Mary Carmel; McCalmont, Mark; Domínguez Robles, Juan; Farmacia y Tecnología Farmacéutica
The COVID-19 pandemic prompted a rapid shift from conventional in-person teaching to remote learning, posing significant challenges for laboratory-based courses. In response, a virtual lab toll was developed for the “Medicinal Substances” module focused on the chemical synthesis of lidocaine. Unlike conventional video demonstrations, this innovative approach integrated interactive, decision-based simulations, allowing students to engage in key procedural choices and experience variable outcomes based on their decisions. The design emphasized critical techniques such as liquid–liquid extractions, a known area of difficulty for students, fostering deeper conceptual understanding and reinforcing decision-making skills essential for future pharmacists and pharmaceutical sciences students. Undergraduates worked through a series of web-based tasks, encountering realistic scenarios that required the careful evaluation of options. Wrong selections led to reduced outcomes and explanatory feedback, encouraging repeated learning without the time constraints of in-person lab sessions. A postsession questionnaire evaluated the effectiveness of the virtual experience. Results demonstrated enhanced comprehension of the synthesis process, improved knowledge with critical procedural steps, and a strong student preference for interactive learning over passive observation. Students highlighted the engagement and clarity provided by the virtual format and expressed interest in its continued use alongside conventional laboratories. This study illustrates the value of interactive virtual laboratories as both a supplement to hands-on practice and a scalable tool for broadening students’ exposure to diverse chemical synthesis techniques. By reducing time demands and resource constraints, virtual laboratories offer a flexible complement to in-person sessions, enhancing chemical education through experiential, decision-based learning.
Optimizing Complex Pharmaceutical Formulations Using Lexicographic Goal Programming: A Case Study on Ultradeformable Liposomes
(2025-06-20) Valverde Cabeza, Sonia; González Rodríguez, Pedro Luis; González Rodríguez, María Luisa; Farmacia y Tecnología Farmacéutica
Introduction: Optimizing pharmaceutical formulations requires advanced approaches to ensure quality, safety, and efficacy. While the desirability function and Weighted Goal Programming balance multiple responses, they lack hierarchical prioritization. Lexicographic Goal Programming overcomes this limitation by optimizing objectives sequentially. This study introduces this tool as an innovative approach for optimizing ultradeformable nanolipo-somes.Method: The study follows six structured steps, including identifying key factors, developing a Design of Experi-ments, defining aspiration levels, assigning priorities, and sequential optimization. It focuses on critical parameters such as vesicle size, zeta potential, and encapsulation efficiency, ensuring a comprehensive hierarchical approach.Results: Lexicographic Goal Programming prioritized zeta potential and encapsulation efficiency first, followed by vesicle size and lower-priority responses. It preserved critical attributes without compromise, efficiently minimizing deviations for both maximization and minimization objectives.Conclusions: Lexicographic Goal Programming provides a robust hierarchical framework for optimization in the pharmaceutical field, effectively managing trade-offs. Ensuring key objectives are met first, it aligns with Quali-ty-by-Design principles. This method is particularly advantageous for complex formulations, such as liposomal drug delivery systems, requiring precise control over vesicle stability, size, and drug encapsulation
Conservation for Teaching: Restoration and Educational Use of an 18th-Century “Albarelo” at the Museum of the History of Pharmacy in Seville (Spain)
(Multidisciplinary Digital Publishing Institute (MDPI), 2025-10-23) Ramos Carrillo, Antonio; Nuñez Valdés, Juan; Ruiz Altaba, Rocío; Farmacia y Tecnología Farmacéutica; Geometría y Topología
The permanent historical-pharmaceutical collection at the Faculty of Pharmacy, University of Seville (Spain), offers visitors a vivid impression of what an apothecary’s shop looked like around the turn of the 19th to the 20th century. In that era, pharmacists manually prepared medicines and stored raw materials in various ceramic containers, including jars, oil cruets, burnias, and albarelos. Each year, the museum receives new donations, such as a recent set of pharmacy jars from a private collection. Most of these are albarelos, with one dating back to the 18th century and others originating from more recent ceramic workshops. During transport from Murcia to Seville, the 18th-century albarelo was accidentally broken. To preserve its historical and artistic value, we commissioned a master potter to restore the piece. Thanks to this intervention, the albarelo is now part of the museum’s exhibition and can be appreciated by students and visitors interested in cultural heritage beyond the pharmaceutical field.
Controlled release of amitriptyline via the transdermal route using SmartReservoirs and hydrogel-forming microneedles
(Elsevier, 2025) Abraham, Abraham M.; Simon, Amitha; Anjani, Qonita Kurnia; Jiang, Yueming; Adhami, Masoud; Domínguez Robles, Juan; Donnelly, Ryan F.; Farmacia y Tecnología Farmacéutica; Engineering and Physical Sciences Research Council (EPSRC). United Kingdom; Ministerio de Ciencia e Innovación (MICIN). España; Universidad de Sevilla
SmartReservoirs (SRs) are novel drug reservoirs made from a cellulose-based matrix for hydrogel-forming microneedles (HF-MNs). SRs can incorporate drug molecules within a cellulose-based matrix in amorphous form. This significantly improves the solubility of poorly soluble drugs, which enhances drug delivery by allowing for rapid dissolution and absorption once the dosage form is administered. In contrast to improving the solubility of hydrophobic drugs, SRs might be used to modify the amorphous/crystalline properties of hydrophilic drugs, thus leading to a controlled release profile. Hence, SRs hold a promise as drug reservoirs for hydrophilic drugs and has not yet been investigated for such drugs; this study explores the transdermal delivery of the hydrophilic model drug amitriptyline hydrochloride (AMT) using SRs. Furthermore, the effect of the cellulose-based matrix on drug loading and release profile was also tested using tissue paper-based (SR-T) and copier paper-based (SR-P) SmartReservoirs. The current research involves the fabrication of HF-MNs and two types of AMT-SRs. Subsequently, a comprehensive characterisation of the HF-MNs and SRs was conducted regarding their morphological features, mechanical and physicochemical properties, amorphous/crystallinity state, interaction with the cellulose matrix, drug distribution, drug loading capacity, and transdermal permeation efficiency. The findings of the study demonstrated that the active pharmaceutical ingredient (API) remained intact within the cellulose matrices of both SRs. The type of cellulose matrix employed had a major influence on the loading and release of the drug. The SR-P demonstrated a significantly enhanced drug loading and release profile compared to the SR-T. The drug content analysis of the SRs revealed that SR-T had approximately 4 mg/ cm2 of AMT, in comparison to SR-P, which had a concentration nearly double that amount. The results of the skin deposition and permeation studies were also consistent, indicating that SR-T combined with HF-MNs deposited approximately 75 μg and permeated <150 μg (~5 % delivered), while SR-P combined with HF-MNs deposited approximately 128 μg and permeated >500 μg of AMT into the skin (~9 % delivered). Ultimately, this work provides substantial evidence to support the use of SRs as a hydrophilic drug reservoir for HF-MNs
Cannabinoid effective targeting of atherosclerotic plaques by optimized-PLGA nanoparticles
(Elsevier, 2025-08-25) Martín Navarro, Lucía; Herrera González, María Dolores; Álvarez Fuentes, Josefa; Claro Cala, Carmen María; Martín Banderas, Lucía; Farmacia y Tecnología Farmacéutica; Farmacología; Junta de Andalucía; European Union (UE); Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. España
Aim While selective CB2 receptor agonists hold significant promise for mitigating inflammation and atherosclerosis, their poor physicochemical properties have hampered clinical translation. To overcome this, we engineered a sophisticated, nanoparticle-based delivery system designed for precise cannabinoid deposition at atheromatous plaque sites. Our approach utilized PEGylated PLGA nanoparticles (NPs), functionalized with a peptide ligand specifically targeting vascular cell adhesion molecule-1 (VCAM-1), a well-established biomarker of atherosclerotic lesions. Methods PEGylated PLGA NPs were synthesized via nanoprecipitation using a blend of PLGA, PLGA-PEG, and PLGA-PEG-Mal polymers. Peptide conjugation was then achieved through a maleimide-click reaction. The resulting functionalized nanoparticles were characterized for their physicochemical properties and evaluated both in vitro (using human vascular endothelial cells), and in vivo (in apolipoprotein E-deficient, ApoE-/-, mice). Results Optimal NP functionalization with the VBP peptide was achieved using a 1:1 maleimide-to-ligand molar ratio in 10 mM HEPES / 0.4 mM EDTA buffer after a 2-hour incubation. In vitro assays demonstrated that these functionalized NPs significantly downregulated the expression of adhesion molecules, inflammatory cytokines, and chemokines, while also successfully restoring oxidative balance in human endothelial cells. Importantly, in vivo experiments demonstrated efficient and site-specific delivery of the functionalized NPs to atheroprone regions in ApoE⁻/⁻ mice, resulting in a significant reduction of atherosclerotic plaque formation in the aortic sinus. Conclusion These findings indicate that this developed nanosystem represents a highly promising strategy for targeted cannabinoid delivery. This breakthrough could significantly contribute to the advancement of novel anti-atherogenic therapies, offering a new avenue for treating atherosclerosis.
Phytochemical Analysis and Therapeutic Potential of Tuberaria lignosa (Sweet) Samp. Aqueous Extract in Skin Injuries
(MDPI, 2025-07-25) González Vázquez, Manuel; Quílez Guerrero, Ana María; Zuzarte, Mónica; Salgueiro, Lígia; Alves Silva, Jorge; González Rodríguez, María Luisa; Puerta Vázquez, Rocío de la; Farmacología; Farmacia y Tecnología Farmacéutica; Caixa Catalunya
Tuberaria lignosa (Sweet) Samp. (Cistaceae) is a herbaceous species native to southwestern Europe, traditionally used to treat wounds, ulcers, and inflammatory or infectious skin conditions. This study aimed to characterize the phytochemical profile of its aqueous leaf extract and evaluate its skin-related in vitro biological activities. The phenolic composition was determined using UHPLC-HRMS/MS, HPLC-DAD, and quantitative colorimetric assays. Antioxidant activity was assessed against synthetic free radicals, reactive oxygen and nitrogen species, transition metals, and pro-oxidant enzymes. Enzymatic inhibition of tyrosinase, hyaluronidase, collagenase, and elastase were evaluated using in vitro assays. Cytocompatibility was tested on human keratinocytes and NIH/3T3 fibroblasts using MTT and resazurin assays, respectively, while wound healing was evaluated on NIH/3T3 fibroblasts using the scratch assay. Antifungal activity was investigated against several Candida and dermatophyte species, while antibiofilm activity was tested against Epidermophyton floccosum. The extract was found to be rich in phenolic compounds, accounting for nearly 45% of its dry weight. These included flavonoids, phenolic acids, and proanthocyanidins, with ellagitannins (punicalagin) being the predominant group. The extract demonstrated potent antioxidant, anti-tyrosinase, anti-collagenase, anti-elastase, and antidermatophytic activities, including fungistatic, fungicidal, and antibiofilm effects. These findings highlight the potential of T. lignosa as a valuable and underexplored source of bioactive phenolic compounds with strong potential for the development of innovative approaches for skin care and therapy.
Venlafaxine-PLGA Nanoparticles Provide a Fast Onset of Action in an Animal Model of Depression Via Nose-to-brain
(Elsevier, 2025) Cayero Otero, María Dolores; Pérez Caballero, Laura; Suárez Pereira, Irene; Hidalgo Figueroa, María; Delgado Sequera, Alejandra; Montesinos, Juan Manuel; Berrocoso, Esther; Martín Banderas, Lucía; Farmacia y Tecnología Farmacéutica; Universidad de Sevilla; Junta de Andalucía
Background: Current treatment of depression is hindered by the delayed onset of the action of antidepressant drugs, often resulting in treatment failure. Therefore, new therapeutic solutions are imperative. Methodology: Venlafaxine-loaded poly(lactic-co-glycolic acid) nanoparticles were produced by a double emulsion-solvent evaporation method. Cellular safety assessment and internalization assays were carried out in vitro in human olfactory neuroepithelium cells. The antidepressant effect of intranasal (nose-to-brain) nanoparticle administration was assessed in animals submitted to an animal model of depression by behavioral tests, including open-field, sucrose preference test and tail suspension test. Results: The drug entrapment efficiency (55–65 %), particle size (190–210 nm), polydispersity index (<0.2), and zeta potential ( 20 mV) of Venlafaxine-loaded poly(lactic-co-glycolic acid) nanoparticles were determined to be adequate. Nanoparticles did not show cytotoxic effects. Cell viability was more than 90 % for all formulations and concentrations assayed. The results of the quantitative and qualitative cell uptake assays were consistent, showing an evident internalization of the nanoparticles into the cells. Furthermore, venlafaxine-loaded nanoparticles administered for just 7 days were able to reverse the phenotype induced by a depressive-like model, showing a significant antidepressant-like effect compared to those treated with free venlafaxine. Conclusions: These findings indicated that intranasal venlafaxine-loaded poly(lactic-coglycolic acid) nanoparticles could become a viable technique for improving venlafaxine brain uptake via nose-to-brain. It could also be a promising nanoplatform for enhancing the treatment of depression.

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