Artículos (Farmacia y Tecnología Farmacéutica)

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Optimising 3D printed medications for rare diseases: In-line mass uniformity testing in direct powder extrusion 3D printing
(ELSEVIER SCIENCE BV; ELSEVIER, 2025) Mora Castaño, Gloria; Rodríguez Pombo, Lucía; Carou-Senra, Paola; Januskaite, Patricija; Millán Jiménez, Mónica; Caraballo Rodríguez, Isidoro; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Ministerio de Universidades; Xunta de Galicia; Fundación Mutua Madrileña
Biotinidase deficiency is a rare inherited disorder characterized by biotin metabolism issues, leading to neurological and cutaneous symptoms that can be alleviated through biotin administration. Three-dimensional (3D) printing (3DP) offers potential for personalized medicine production for rare diseases, due to its flexibility in designing dosage forms and controlling release profiles. For such point-of-care applications, rigorous quality control (QC) measures are essential to ensure precise dosing, optimal performance, and product safety, especially for low personalized doses in preclinical and clinical studies. In this work, we addressed QC challenges by integrating a precision balance into a direct powder extrusion pharmaceutical 3D printer (M3DIMAKER™) for real-time, in-line mass uniformity testing, a critical quality control step. Small and large capsule-shaped biotin printlets (3D printed tablets) for immediate- and extended-release were printed. The integrated balance monitored and registered each printlet’s weight, identifying any deviations from acceptable limits. While all large printlet batches met mass uniformity criteria, some small printlet batches exhibited weight deviations. In vitro release studies showed large immediate-release printlets releasing 82% of biotin within 45 min, compared to 100% for small immediate-release printlets. For extended-release formulations, 35% of the drug was released from small printlets, whereas 24% was released from large printlets at the same time point. The integration of process analytical technology tools in 3DP shows promise in enhancing QC and scalability of personalized dosing at the point-of-care, demonstrating successful integration of a balance into a direct powder extrusion 3D printer for in-line mass uniformity testing across different sizes of capsule-shaped printlets.
3D-printed implants loaded with acriflavine for glioblastoma treatment
(Elsevier, 2024-09-12) Korelidou, Anna; Domínguez Robles, Juan; Islam, Rayhanul; Donnelly, Ryan F.; Coulter, Jonathan A.; Larrañeta, Eneko; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; European Union (UE). H2020; Agencia Estatal de Investigación. España; Ministerio de Ciencia e Innovación (MICIN). España
Drug delivery routes play an essential role in determining the efficacy and safety of medications. This study focused on the development and optimization of 3Dprinted reservoir type implants as a combinational therapy drug delivery system for Glioblastoma Multiforme (GBM) post-surgery, possessing also antibacterial properties. In this study, we used a multimodal agent, Acriflavine (ACF) as an alternative drug to treat GBM. To date, ACF is used only as an antiseptic agent, although it has been shown to possess strong anticancer activities. ACF and a low molecular weight PCL were loaded into 3D-printed reservoir-type implants for sustained drug delivery. The study demonstrated that ACF implants exhibited sustained drug release kinetics, with faster release during the initial 30 days, followed by a gradual decrease over 90 days. This controlled release profile enhances the effectiveness of ACF delivery to tumour targets while minimizing side effects associated with systemic administration. In vitro experiments confirmed the inhibitory activity of ACF against GBM cells compared to non-tumour cells. The study also highlighted the bacteriostatic effects of ACF, making the implants potentially useful for post-surgery infection management, particularly against S. aureus, a common bacterial infection associated with brain surgery. The long-term drug-release capabilities of the implants make them attractive candidates for both tumour inhibition and antibacterial treatment. The study suggests that the developed ACF delivery systems have the potential for future clinical studies. Their ability to provide increased drug efficacy without systemic toxicity makes them promising candidates for cancer therapy and post-surgery infection management.
Halloysite Nanotube-Based Delivery of Pyrazolo[3,4-d]pyrimidine Derivatives for Prostate and Bladder Cancer Treatment
(Multidisciplinary Digital Publishing Institute (MDPI), 2024) Massaro, M.; Ciani, R.; Grossi, G.; Cavallaro, G.; Melo Barbosa, Raquel de; Falesiedi, M.; Fortuna, C. G.; Carbone, A.; Schenone, S.; Sánchez Espejo, R.; Viseras, C.; Vago, R.; Riela, S.; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
Background/Objectives: The development of therapies targeting unregulated Src signaling through selective kinase inhibition using small-molecule inhibitors presents a significant challenge for the scientific community. Among these inhibitors, pyrazolo[3,4-d]pyrimidine heterocycles have emerged as potent agents; however, their clinical application is hindered by low solubility in water. To overcome this limitation, some carrier systems, such as halloysite nanotubes (HNTs), can be used. Methods: Herein, we report the development of HNT-based nanomaterials as carriers for pyrazolo[3,4-d]pyrimidine molecules. To achieve this objective, the clay was modified by two different approaches: supramolecular loading into the HNT lumen and covalent grafting onto the HNT external surface. The resulting nanomaterials were extensively characterized, and their morphology was imaged by high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM). In addition, the kinetic release of the molecules supramolecularly loaded into the HNTs was also evaluated. QSAR studies were conducted to elucidate the physicochemical and pharmacokinetic properties of these inhibitors, and structure-based virtual screening (SBVS) was performed to analyze their binding poses in protein kinases implicated in cancer. Results: The characterization methods demonstrate successful encapsulation of the drugs and the release properties under physiological conditions. Furthermore, QSAR studies and SBVS provide valuable insights into the physicochemical, pharmacokinetic, and binding properties of these inhibitors, reinforcing their potential efficacy. Conclusions: The cytotoxicity of these halloysite-based nanomaterials, and of pure molecules for comparison, was tested on RT112, UMUC3, and PC3 cancer cell lines, demonstrating their potential as effective agents for prostate and bladder cancer treatment.
Avances terapéuticos en el abordaje de las fisuras anales: explorando la sinergia entre Farmacología y Nanotecnología
(Universidad de Granada, 2024) Pazmiño Chiluiza, Carlos Ostwaldo; González Rodríguez, María Luisa; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
Introducción: La fisura anal es una patología proctológica frecuente, cronificante, caracterizada por la presencia de lesiones dolorosas ocasionadas por la hipertonía del musculo liso del esfínter anal interno. A pesar de su impac-to, los tratamientos convencionales disponibles pueden ser limitados en términos de reproducibilidad, eficacia y tolerabilidad a largo plazo. Debido a ello, la exploración de nuevas terapias farmacológicas, en sincronía con nano-vehículos que permitan su direccionamiento específico al lugar de acción, ofrecen una alternativa potencial para mejorar su tratamiento.Método: Se plantea como un estudio de tipo retrospectivo y longitudinal.Resultados: Se aplican diferentes abordajes terapéuticos, desde medidas higiénico-sanitarias, tratamientos far-macológicos no invasivos, hasta la cirugía, la mayoría de ellos dirigidos a disminuir la hipertonía. Los fármacos habituales a nivel hospitalario son lidocaína, diltiazem, nifedipino, nimodipino, nitrato de isosorbide y la toxina botulínica. Aprovechando las ventajas de la nanotecnología farmacéutica en la mejora de la eficacia terapéutica, disminuyendo los efectos adversos generados en la administración sistémica y aumentando la tasa de curación, se han encontrado estudios sobre la aplicación de nanopartículas poliméricas, vesiculares y micro-nano emulsiones para vehiculizar fármacos para el tratamiento sintomático de la fisura anal. Algunas formulaciones cuentan con autorización sanitaria y otras se encuentran en fase de investigación.Conclusiones: Se ha evidenciado que las nuevas formulaciones, especialmente aquellas basadas en nanotecno-logía, muestran un potencial significativo para mejorar la cicatrización de las fisuras en comparación con los trata-mientos convencionales. No obstante, son necesarios estudios sobre el uso seguro de estos sistemas antes de su implementación clínica generalizada.
Factores asociados a la mortalidad en pacientes hospitalizados por COVID-19 en España: datos del Registro Español de Resultados de Farmacoterapia frente a COVID-19 (RERFAR)
(Sociedad Española de Farmacia Hospitalaria, 2022) Olry de Labry Lima, Antonio; Sáez de la Fuente, Javier; Abdel-Kader Martín, Laila; Alegre del Rey, Emilio Jesús; García Cabrera, Emilio; Sierra Sánchez, Jesús F.; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Universidad de Sevilla. Departamento de Medicina Preventiva y Salud Pública
Objetivo: Determinar las características basales que se asocian a una mayor mortalidad a los 42 días en aquellos pacientes hospitalizados por COVID-19 en España. Método: Cohorte prospectiva de pacientes COVID-19 hospitalizados. La variable dependiente fue la mortalidad a los 42 días. Además, se recogieron características demográficas, clínicas, comorbilidades, tratamiento habitual, intervenciones de soporte y tratamientos en las primeras 48 horas del ingreso. Para determinar la asociación con la mortalidad, se realizó un análisis multivariante mediante regresión logística. Resultados: Se incluyeron 15.628 pacientes, de ellos falleció el 18,2% (n = 2.806). El análisis multivariante mostró que las variables asociadas significativamente (p < 0,05) con la mortalidad al ingreso fueron: proceder de un centro sociosanitario (odds ratio OR 1,9), frecuencia respiratoria (odds ratio 1,5), gravedad de neumonía (CURB-65) moderada (odds ratio 1,7) o alta (odds ratio 2,9), transaminasa aspartato aminotransferasa ≥ 100 UI/l (odds ratio 2,1), lactato-deshidrogenasa ≥ 360 UI/l (odds ratio 1,6), procalcitonina > 0,5 ng/ml (odds ratio 1,8), creatina- quinasa ≥ 294 U/l (odds ratio 1,5), dímero D > 3.000 ng/ml (odds ratio 1,5), hemoglobina < 11,6 g/dl (odds ratio 1,4) y proteína C reactiva > 120 mg/l (odds ratio 1,2), necesidad de soporte respiratorio en las primeras 48 horas (odds ratio 2,0 de oxigenoterapia; odds ratio 2,8 ventilación no invasiva y odds ratio 3,5 ventilación mecánica) y tratamiento con interferón-beta (odds ratio 1,5). Por el contrario, ser menor de 80 años se asoció a una menor mortalidad. Conclusiones: El análisis del Registro Español de Resultados de farmacoterapia frente a COVID-19 muestra que los factores asociados a peor pronóstico son: mayor edad, valoración mediante la escala CURB‑65, el nivel de requerimiento de soporte respiratorio, neumonía grave (CURB‑65), hipertransaminasemia, elevación de creatina-quinasa, lactato- deshidrogenasa, y dímero-D, anemia y elevación de la frecuencia respiratoria.
Innovations in Cancer Therapy: Endogenous Stimuli-Responsive Liposomes as Advanced Nanocarriers
(MDPI, 2025-02-13) Torres, Jazmín; Valenzuela Oses, Johanna Karina; Rabasco Álvarez, Antonio María; González Rodríguez, María Luisa; García, Mónica Cristina; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Agencia Nacional de Promoción Científica y Tecnológica. Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). Argentina; Universidad de Córdoba. Argentina
Recent advancements in nanotechnology have revolutionized cancer therapy—one of the most pressing global health challenges and a leading cause of death—through the development of liposomes (L), lipid-based nanovesicles known for their biocompatibility and ability to encapsulate both hydrophilic and lipophilic drugs. More recent innovations have led to the creation of stimuli-responsive L that release their payloads in response to specific endogenous or exogenous triggers. Dual- and multi-responsive L, which react to multiple stimuli, offer even greater precision, improving therapeutic outcomes while reducing systemic toxicity. Additionally, these smart L can adjust their physicochemical properties and morphology to enable site-specific targeting and controlled drug release, enhancing treatment efficacy while minimizing adverse effects. This review explores the latest advancements in endogenous stimuli-responsive liposomal nanocarriers, as well as dual- and multi-responsive L that integrate internal and external triggers, with a focus on their design strategies, mechanisms, and applications in cancer therapy.
Lipid nanoparticles as an emerging platform for cannabinoid delivery: physicochemical optimization and biocompatibility
(Taylor & Francis, 2016) Durán Lobato, María Matilde; Martín Banderas, Lucía; Lopes, R.; Gonçalves, L.M.D.; Fernández Arévalo, María Mercedes; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Junta de Andalucía; Fundação para a Ciência e a Tecnologia. Portugal
This work aims at developing and optimizing a valuable oral delivery carrier for the cannabinoid derivative CB13, which presents a high therapeutic potential in chronic pain states that respond poorly to conventional analgesics, but also shows highly unfavorable physicochemical properties. CB13-loaded lipid nanoparticles (LNP) formulations were developed through solvent-emulsion evaporation and optimized in terms of physicochemical properties, long-term stability, integrity under gastric simulated conditions and in vitro interaction with NIH 3T3, HEK 293T and Caco-2 cells. An optimized formulation of LNP containing CB13 was obtained from a wide range of conditions assayed and analyzed. The selection of the lipid core, production conditions and the inclusion of lecithin proved to be key factors for the final properties of encapsulation, integrity and performance of the carriers. The LNP formulation proposed proved to be a promising carrier for the oral delivery of CB13, a cannabinoid with high therapeutic potential in chronic pain states that currently lack a valid oral treatment.
Comparative study of chitosan- and PEG-coated lipid and PLGA nanoparticles as oral delivery systems for cannabinoids
(Elsevier, 2015) Durán Lobato, María Matilde; Martín Banderas, Lucía; Gonçalves, Lídia M.D.; Fernández Arévalo, María Mercedes; Almeida, Antonio J.; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Junta de Andalucía; imed - Research Institute for Medicines. Portugal
The cannabinoid derivative 1-naphthalenyl[4-(pentyloxy)-1-naphthalenyl]methanone (CB13) has an important therapeutic potential as analgesic in chronic pain states that respond poorly to conventional drugs. However, the incidence of its mild-to-moderate and dose-dependent adverse effects, as well as its pharmacokinetic profile, actually holds back its use in humans. Thus, the use of a suitable carrier system for oral delivery of CB13 becomes an attractive strategy to develop a valuable therapy. Polymeric poly(lactic-co-glycolic) acid (PLGA) and lipid nanoparticles (LNPs) are widely studied delivery vehicles that improve the bioavailability of lipophilic compounds and present special interest in oral delivery. Their surface can be modified to improve the adhesion of particles to the oral mucosa and increase their circulation time in blood with additives such as chitosan (CS) and polyethylene glycol (PEG), which can be feasibly incorporated onto these particles in a post-production step. In this work, CS- and PEG-modified polymeric PLGA and LNPs were successfully obtained and comparatively evaluated under the same experimental conditions as oral carriers for CB13. All the formulations presented adequate blood compatibility and absence of cytotoxicity in Caco-2 cells. Coating with CS led to a higher interaction with Caco-2 cells and a limited uptake in THP1 cells, while coating with PEG led to a limited uptake in Caco-2 cells and strongly prevented THP1 cells uptake. The performance of each formulation is discussed as a comparison of the potential of these carriers as oral delivery systems of CB13.
Engineering of Δ9-tetrahydrocannabinol delivery systems based on surface modified-PLGA nanoplatforms
(Elsevier, 2014-11-01) Martín Banderas, Lucía; Muñoz Rubio, Inmaculada; Álvarez Fuentes, Josefa; Durán Lobato, María Matilde; Arias, José L.; Holgado Villafuerte, María Ángeles; Fernández Arévalo, María Mercedes; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Junta de Andalucía; Instituto de Salud Carlos III
The objective of this work is to develop a nanoplatform that can potentiate the oral administration of Δ9-tetrahidrocannabinol, a highly lipophilic active agent with very promising antiproliferative and antiemetic activities. To that aim, colloidal carriers based on the biodegradable and biocompatible poly(d,l-lactide-co-glycolide) were investigated. Such delivery systems were prepared by nanoprecipitation, and nanoparticle engineering further involved surface modification with a poly(ethylene glycol), chitosan, or poly(ethylene glycol)-chitosan shells to assure the greatest uptake by intestinal cells and to minimize protein adsorption. Characterization of the nanoplatforms included particle geometry (size and shape), electrophoretic properties (surface charge). Δ9-tetrahydrocannabinol vehiculization capabilities (loading and release), blood compatibility, and cellular uptake and cytotoxicity. Results were satisfactorily used to define the optimum engineering conditions to formulate surface modified nanoparticles for the efficient oral administration of Δ9-tetrahydrocannabinol. To the best of our knowledge, this is the first time that biocompatible polymeric nanoparticles have been formulated for Δ9-tetrahydrocannabinoldelivery.
Biocompatible gemcitabine-based nanomedicine engineered by Flow Focusing® for efficient antitumor activity
(Elsevier, 2013) Martín Banderas, Lucía; Sáez-Fernández, Eva; Holgado Villafuerte, María Ángeles; Durán Lobato, María Matilde; Prados, José C.; Melguizo, Consolación; Arias, José L.; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Instituto de Salud Carlos III
We investigated the incorporation of gemcitabine into a colloidal carrier based on the biodegradable and biocompatible poly(d,l-lactide-co-glycolide) (PLGA) to optimize its anticancer activity. Two synthesis techniques (double emulsion/solvent evaporation, and Flow Focusing®) were compared in terms of particle geometry, electrophoretic properties (surface charge), gemcitabine vehiculization capabilities (drug loading and release), blood compatibility, and in vitro antitumor activity. To the best of our knowledge, the second formulation methodology (Flow Focusing®) has never been applied to the synthesis of gemcitabine-loaded PLGA particles. With the aim of achieving the finest (nano)formulation, experimental parameters associated to these preparation procedures were analyzed. The electrokinetics of the particles suggested that the chemotherapy agent was incorporated into the polymeric matrix. Blood compatibility was demonstrated in vitro. Flow Focusing® led to a more appropriate geometry, higher gemcitabine loading and a sustained release profile. In addition, the cytotoxicity of gemcitabine-loaded particles prepared by Flow Focusing® was tested in MCF-7 human breast adenocarcinoma cells, showing significantly greater antitumor activity compared to the free drug and to the gemcitabine-loaded particles synthesized by double emulsion/solvent evaporation. Thus, it has been identified the more adequate formulation conditions in the engineering of gemcitabine-loaded PLGA nanoparticles for the effective treatment of tumours.
Functional PLGA NPs for Oral Drug Delivery: Recent Strategies and Developments
(Bentham Science, 2013) Martín Banderas, Lucía; Durán Lobato, María Matilde; Muñoz Rubio, Inmaculada; Álvarez Fuentes, Josefa; Fernández Arévalo, María Mercedes; Holgado Villafuerte, María Ángeles; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Junta de Andalucía
This article presents the potential of PLGA nanoparticles for the oral administration of drugs. Different strategies are used to improve oral absorption of these nanoparticles. These strategies are based on modification of nanoparticle surface properties. They can be achieved either by coating the nanoparticle surface with stabilizing hydrophilic bioadhesive polymers or surfactants, or by incorporating biodegradable copolymers containing a hydrophilic moiety. Some substances such as chitosan, vitamin E, methacrylates, lectins, lecithins, bile salts and RGD molecules are employed for this purpose. Of especial interest are nanoparticles production methods and, in order to improve oral bioavailability, the mechanism of each additive.
Cannabinoids as Emergent Therapy Against COVID-19
(Mary Ann Liebert, 2022-10-12) McGrail, Joseph; Martín Banderas, Lucía; Durán Lobato, María Matilde; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory distress syndrome coronavirus 2 (SARS-Cov-2), was identified for the first time in late 2019 in China, resulting in a global pandemic of massive impact. Despite a fast development and implementation of vaccination strategies, and the scouting of several pharmacological treatments, alternative effective treatments are still needed. In this regard, cannabinoids represent a promising approach because they have been proven to exhibit several immunomodulatory, anti-inflammatory, and antiviral properties in COVID-19 disease models and related pathological conditions. This mini-review aims at providing a practical brief overview of the potential applications of cannabinoids so far identified for the treatment and prevention of COVID-19, finally considering key aspects related to their technological and clinical implementation.
Preparation and In Vivo Evaluation of Rosmarinic Acid-Loaded Transethosomes After Percutaneous Application on a Psoriasis Animal Model
(Springer Nature, 2021) Rodríguez Luna, Azahara María; Talero Barrientos, Elena Mª; Ávila Román, Francisco Javier; Fernández Romero, Ana María; Rabasco Álvarez, Antonio María; Motilva Sánchez, Virginia; González Rodríguez, María Luisa; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Junta de Andalucía; Universidad de Sevilla
The topical use of rosmarinic acid (RA) in skin inflammatory pathologies is restricted due to its poor water solubility, poor permeability, and chemical instability. In this study, RA-loaded transethosomes-in-Carbopol® formulations have been developed to evaluate its anti-inflammatory activity on imiquimod-induced psoriasis-like skin inflammation in mice. In vitro release profiles demonstrated sustained behavior due to the retentive action of gel and the entrapment of RA into the vesicles. However, the low viscosity of the combined formulation increased the drug release rate. Animal evaluation of anti-inflammatory activity demonstrated that transethosomes-in-gel containing dexamethasone (Dex-TE-Gel), as positive control, showed effect in all the pro-inflammatory parameters evaluated, evidencing that these drug-loaded nanocarriers have been effectively reached the site of action. In addition, transethosomes-in-gel containing RA (RA-TE-Gel) formulations produced a great reduction in the punch edema (P < 0.001) and in TNF-α and IL-6 (P < 0.05). However, non-significant differences were obtained for IL-1β, IL17, and MPO. Despite the protecting effect of Carbopol® and transethosomes on oxidation index and antioxidant activity of RA over the 7 days of treatment, however, a degradation process of this antioxidant to caffeic acid may be the cause of these in vivo results. We have also checked that the pH existing into the intercellular space of damaged cells (pH 6.8) may be affecting. Therefore, our results suggest that RA-TE-Gel could act as an effective RA formulation for skin delivery; further studies will help to understand the loss of activity at the cellular level.
Drug diffusion from disperse systems with a hydrophobically modified polysaccharide: Enhancer (R) vs Franz cells
(Elsevier Science Ltd, 2012-09-13) Lucero Muñoz, María Jesús; Claro Cala, Carmen María; Casas Delgado, Marta; Jiménez-Castellanos Ballesteros, María Rosa; Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
This study assesses the capacity of a new hydrophobically modified polysaccharide –hydroxypropyl cellulose–methyl methacrylate – to control drug release in semisolid formulations. The dispersed sys tems contain the new polymer, Igepal®CO520 as surfactant and theophylline as model drug at three concentrations (0.5, 1 and 1.5%, w/w). Drug release study shows that the systems containing 0.5% (w/w) of drug have faster release and higher diffusion coefficient than the other two concentrations. These results can be explained by two different structures (“relaxed” and “structured”) found from a rheologi cal point of view. Also, this paper compares two different devices for testing drug release and diffusion. It has been obtained more reliable and reproducible results with Enhancer Cell®respect to Franz diffusion cell. In both cases, Fickian diffusion was the mechanism predominant for all systems. Finally, the utility of this polymer has been demonstrated to make three-dimensional gel structure and control theophylline release from systems in topical application.
Rheological and mechanical properties of hydrophilic dispersions using a new hydrophobically modified polymer and Igepal (R) CO520
(Elsevier, 2011-08-15) Lucero Muñoz, María Jesús; Claro Cala, Carmen María; Casas Delgado, Marta; Jiménez Castellanos, María Rosa; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología; Instituto de Biomedicina de Sevilla (IBIS); Universidad de Sevilla. CTS-1015: Desarrollo galénico de medicamentos y productos cosméticos; Universidad de Sevilla. CTS-547: Caracterización y optimización estadística de medicamentos; Universidad de Sevilla. CTS-1074: Inmunonutrición e inmunometabolismo
Hydroxypropyl cellulose-methyl methacrylate and non-ionic surfactant Igepal (R) CO520 (20-25% (w/w)) have been characterized in aqueous-based dispersions for topical application systems. The systems have similar viscosity curves independent of the surfactant's concentration, showing shear-thinning fluids. Also, the elastic and viscous moduli are constant and independent of critical stress values applied; however, the storage modulus was always higher than the loss modulus. Both parameters showed a slightly dependence on the applied frequency, indicating a gel-like behavior. The complex dynamic viscosity increases until 23% (w/w) of surfactant, keeps then constant. The hardness, compressibility and adhesiveness parameters increase when increase the Igepal (R) CO520 concentration. The adhesiveness properties are 18-47% higher than the compressibility ones, with low values for hardness (similar to 0.4 N). While fracture and Hencky's strain values increase when increase the surfactant concentration, fracture work decreased, and no relation is found to deformability modulus. Also, the dispersed system with 20% (w/w) of Igepal CO520 has less stiffness than with 25% (w/w). (C) 2011 Elsevier Ltd. All rights reserved.
Reservoir-type intranasal implants for sustained release of risperidone: A potential alternative for long-term treatment of schizophrenia
(Elsevier, 2024-09) Utomo, Emilia; Li, Linlin; Gao, Jiaqi; Anjani, Qonita Kurnia; Picco, Camila J.; Moreno-Castellanos, Natalia; Donnelly, Ryan F.; Domínguez Robles, Juan; Larrañeta, Eneko; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Engineering & Physical Sciences Research Council (EPSRC); Ministerio de Ciencia e Innovación (MICIN). España
To overcome the challenges of the blood-brain barrier for drug delivery to the central nervous system (CNS), intranasal implants were developed to improve the management of CNS conditions, such as schizophrenia. In the present work, we developed and characterised a drug-containing implant consisting of two parts: a core layer made from risperidone (RIS) and water-soluble polymers, including poly(vinylpyrrolidone) (PVP) and poly(ethylene glycol) (PEG), and a coating layer made of poly(caprolactone) (PCL) membrane. The obtained implants, where the core layer contained 75 % w/w risperidone, were characterised using several techniques: scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR). Moreover, the in vitro release profile of RIS was studied, showing that the PCL membrane could extend the release of RIS from 2 days up to 100 days. The in vitro release profile of the PCL-coated implant exhibited a linear release over the first 10 days, followed by a slower release rate that reached another linear phase up to 40 days. Subsequently, the drug release rates progressively slowed down. Finally, the results of in vitro biocompatibility studies indicated that the intranasal implants were biocompatible and non-cytotoxic. These findings suggest that the implants prepared in this work have the potential to provide long-acting drug delivery for targeting the brain.
Efficacy assessment of liposome crosslinked hyaluronic acid and standard hyaluronic acid eye drops for dry eye disease management: a comparative study employing the ocular surface analyzer and subjective questionnaires
(Frontiers Media S.A., 2024-06-26) Sánchez González, José María; Hita Cantalejo, María Concepción de; González Rodríguez, María Luisa; Fernández-Trueba-Fagúndez, Ana; Ballesteros-Sánchez, Antonio; Martínez-Pérez, Clara; Caro-Díaz, Romina; Montiel Guzmán, Carla; González-Oyarce, María Fernanda; Sánchez González, María del Carmen; Universidad de Sevilla. Departamento de Física de la Materia Condensada; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
Introduction: Dry eye disease (DED) is a prevalent condition causing ocular discomfort and visual disturbances, often managed with artificial tears. This study aimed to assess and compare the efficacy of eye drops containing Crosslinked Hyaluronic Acid (CHA) with liposomes and crocin and standard Hyaluronic Acid (HA) for DED management. Methods: A single-blind, longitudinal study was conducted on 24 participants (48 eyes), randomized to receive one of the two treatments. Ocular health measures, including the ocular surface disease index (OSDI) and the standard patient evaluation of eye dryness (SPEED) scores, were assessed at baseline and 6 weeks post-treatment using the Ocular Surface Analyzer. Results: CHA achieved a lipid layer thickness increase of 1.29 ± 1.08 Guillon pattern degree (p < 0.01), FNIBUT increase 0.64 ± 0.77 s (p < 0.01), MNIBUT increase1.28 ± 4.74 s (p = 0.19), OSDI decrease 11.72 ± 6.73 score points (p < 0.01) and SPEED decrease 1.16 ± 5.05 score points (p = 0.27). Significant reductions in the OSDI and SPEED scores post-treatment were observed with both treatments, indicating their effectiveness. Conclusion: CHA with liposomes exhibits superior efficacy compared to standard HA eye drops in the management of DED. These findings highlight the potential for personalized treatment strategies incorporating CHA, indicating a more effective approach to DED management. However, further research is required to validate these results and investigate the long-term effects, which may pave the way for a data-driven and optimized approach to managing DED.
Deepvirusclassifier: a deep learning tool for classifying SARS-CoV-2 based on viral subtypes within the coronaviridae family
(Springer Nature, 2024-07-05) Azevedo, Karolayne S.; de Souza, Luísa C.; Coutinho, Maria G. F.; Melo Barbosa, Raquel de; Fernandes, Marcelo A. C.; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Purpose: In this study, we present DeepVirusClassifier, a tool capable of accurately classifying Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral sequences among other subtypes of the coronaviridae family. This classification is achieved through a deep neural network model that relies on convolutional neural networks (CNNs). Since viruses within the same family share similar genetic and structural characteristics, the classification process becomes more challenging, necessitating more robust models. With the rapid evolution of viral genomes and the increasing need for timely classification, we aimed to provide a robust and efficient tool that could increase the accuracy of viral identification and classification processes. Contribute to advancing research in viral genomics and assist in surveilling emerging viral strains. Methods: Based on a one-dimensional deep CNN, the proposed tool is capable of training and testing on the Coronaviridae family, including SARS-CoV-2. Our model’s performance was assessed using various metrics, including F1-score and AUROC. Additionally, artificial mutation tests were conducted to evaluate the model’s generalization ability across sequence variations. We also used the BLAST algorithm and conducted comprehensive processing time analyses for comparison. Results: DeepVirusClassifier demonstrated exceptional performance across several evaluation metrics in the training and testing phases. Indicating its robust learning capacity. Notably, during testing on more than 10,000 viral sequences, the model exhibited a more than 99% sensitivity for sequences with fewer than 2000 mutations. The tool achieves superior accuracy and significantly reduced processing times compared to the Basic Local Alignment Search Tool algorithm. Furthermore, the results appear more reliable than the work discussed in the text, indicating that the tool has great potential to revolutionize viral genomic research. Conclusion: DeepVirusClassifier is a powerful tool for accurately classifying viral sequences, specifically focusing on SARS-CoV-2 and other subtypes within the Coronaviridae family. The superiority of our model becomes evident through rigorous evaluation and comparison with existing methods. Introducing artificial mutations into the sequences demonstrates the tool’s ability to identify variations and significantly contributes to viral classification and genomic research. As viral surveillance becomes increasingly critical, our model holds promise in aiding rapid and accurate identification of emerging viral strains.
Cryopreserved nanostructured fibrin-agarose hydrogels are efficient and safe hemostatic agents
(Nature Research, 2024-08-21) Casado, Carlos; Cepeda-Franco, Carmen; Pereira Arenas, Sheila; Suárez, María Dolores; Gómez Bravo, Miguel Ángel; Alaminos, Miguel; Chato-Astrain, Jesús;; Fernández Muñoz, Beatriz; Campos-Cuerva, Rafael; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Universidad de Sevilla. Departamento de Cirugía; Instituto de Salud Carlos III; Universidad de Sevilla
Uncontrolled bleeding during surgery is associated with high mortality and prolonged hospital stay, necessitating the use of hemostatic agents. Fibrin sealant patches offer an efficient solution to achieve hemostasis and improve patient outcomes in liver resection surgery. We have previously demonstrated the efficacy of a nanostructured fibrin-agarose hydrogel (NFAH). However, for the widespread distribution and commercialization of the product, it is necessary to develop an optimal preservation method that allows for prolonged stability and facilitates storage and distribution. We investigated cryopreservation as a potential method for preserving NFAH using trehalose. Structural changes in cryopreserved NFAH (Cryo-NFAH) were investigated and comparative in vitro and in vivo efficacy and safety studies were performed with freshly prepared NFAH. We also examined the long-term safety of Cryo-NFAH versus TachoSil in a rat partial hepatectomy model, including time to hemostasis, intra-abdominal adhesion, hepatic hematoma, inflammatory factors, histopathological variables, temperature and body weight, hemocompatibility and cytotoxicity. Structural analyses demonstrated that Cryo-NFAH retained most of its macro- and microscopic properties after cryopreservation. Likewise, hemostatic efficacy assays showed no significant differences with fresh NFAH. Safety evaluations indicated that Cryo-NFAH had a similar overall profile to TachoSil up to 40 days post-surgery in rats. In addition, Cryo-NFAH demonstrated superior hemostatic efficacy compared with TachoSil while also demonstrating lower levels of erythrolysis and cytotoxicity than both TachoSil and other commercially available hemostatic agents. These results indicate that Cryo-NFAH is highly effective hemostatic patch with a favorable safety and tolerability profile, supporting its potential for clinical use.
Improved antileishmanial activity and cytotoxicity of a novel nanotherapy for N-iodomethyl-N,N-dimethyl-N-(6,6-diphenylhex-5-en-1-yl)ammonium iodide
(Elsevier, 2021-02) Fernández, Maritza; Holgado Villafuerte, María Ángeles; Cayero Otero, María Dolores; Pineda, Tatiana; Yepes, Lina M; Gaspar, Diana P.; Almeida, António J.; Robledo, Sara M; Martín Banderas, Lucía; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Investigación y Desarrollo Tecnológico en Nanomedicina CTS-480 (Universidad de Sevilla)
The N-iodomethyl-N, N-Dimethyl-N-(6,6-diphenylhex-5-en-1-yl) ammonium iodide (C6I) is a new chemical entity (NCE) with demonstrated in vitro and in vivo antileishmanial activity. As many others NCE, C6I is poorly water soluble (Class II of the Biopharmaceutical Classification System), thus its oral administration is potentially compromised. To overcome the issue, nanotechnology is a real and useful tool. Moreover, nanotechnology can improve C6I internalization by macrophages, the drug targets, therefore increasing its antileishmanial activity. The present work aimed to develop a potential suitable oral nanodrug delivery system for C6I to improve its antileishmanial activity. For this purpose, polymeric and solid lipid nanoparticles were developed. Polylactic-co-glycolic acid polyester (PLGA) were prepared by nanoprecipitation while solid lipid nanoparticles made of glycerol tripalmitate (Trp) and glyceryl tristearate (Trs) were obtained by emulsion–solvent evaporation method. Physicochemical characterization of all formulations was performed, as well as stability studies. A lyophilization procedure was also established. Biological activity was evaluated by antileishmanial activity and cytotoxicity in vitro assays. Five types of commercial PLGA to encapsulate C6I were tested. The best results were obtained using PLGA 752S and d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS), the water-soluble form of vitamin E. Particles around 220 nm in diameter and encapsulation efficiency (EE) up to 60% were obtained. Solid lipid nanoparticles based on Trs and Trp lipids were also in the nanoscale showing a low polydispersity index and EE% >60%. Both types of nanoformulations, polymeric and lipidic, thd C6I cytotoxicity in human and hamster macrophages cell cultures. In vitro assays with PLGA loaded- C6I showed a noticeable improved antileishmanial activity on on intracellular amastigotes of L. (V.) panamensis, with the following EC50 values: PLGA <<< Trs-SLN<< free C6I < Trp-SLN. In conclusion, PLGA nanoformulation could be a suitable candidate for preclinical evaluation in animal model.

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