Artículos (Farmacia y Tecnología Farmacéutica)

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

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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; Universidad de Sevilla. Departamento de 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.
Preparation, Characterisation, and Testing of Reservoir-based Implantable Devices Loaded with Tizanidine and Lidocaine
(Springer, 2025) Picco, Camila J.; Bhalerao, Mihir S.; Fandino, Octavio E.; Magill, Elizabeth R.; Anjani, Qonita Kurnia; Acheson, Jonathan G.; Donnelly, Ryan F.; Domínguez Robles, Juan; Larrañeta, Eneko; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Engineering and Physical Sciences Research Council (UK); Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Universidad de Sevilla
Multiple sclerosis is a chronic neuroimmunological disorder that causes progressive disability, primarily in young adults. It places a significant burden on healthcare systems due to high medication costs and long-term care needs. Implantable devices offer a promising alternative for delivering sustained drug doses in the treatment of chronic conditions. This study introduces a novel long-acting subcutaneous implant for dual-drug delivery: tizanidine (TZ) for spasticity management and lidocaine (LD) for post-insertion pain relief. Reservoir-type implants were developed with TZ in the core and LD in the shell. Two fabrication methods—direct compression and vacuum compression moulding (VCM)—were evaluated for TZ-loaded pellets (3 mm diameter, ~10 mm length) using TZ base and TZ hydrochloride. Pellets were encapsulated inside a biodegradable polycaprolactone (PCL) tubular membrane to control drug release. Direct compression pellets, made with poly(vinyl pyrrolidone) and hydroxypropyl-β-cyclodextrin, disintegrated quickly, releasing TZ over 20 days. VCM pellets, formulated with PCL or PCL/poly(ethylene glycol) (PEG), offered prolonged release: up to 200 days for TZ base and 80 days for TZ hydrochloride. Adding PEG accelerated TZ release, reducing duration to 20 days (TZ base) and 125 days (TZ hydrochloride). LD was incorporated into the PCL membrane, providing up to three days of sustained release. Physicochemical analysis confirmed formulation homogeneity and no covalent interactions. These findings highlight the potential of this implant system for MS-related spasticity management, supporting further research into long-acting implants to improve treatment adherence and patient outcomes.
Evaluating the Potential of Ultrasound-assisted Compression for Crafting Implantable Drug Delivery Systems
(Elsevier, 2025) Millán Jiménez, Mónica; Sánchez Díaz, Elena; Mora Castaño, Gloria; Kurnia Anjani, Qonita; García Martín, Adela; Caraballo Rodríguez, Isidoro; Larrañeta, Eneko; Domínguez Robles, Juan; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Ministerio de Ciencia e Innovación (MICIN). España; Universidad de Sevilla; Engineering and Physical Sciences Research Council (UK)
This study aimed to evaluate the feasibility of using ultrasound-assisted compression (USAC) for manufacturing implantable drug delivery systems (IDDS). USAC integrates the principles of traditional compression techniques with the application of ultrasound waves. The combined mechanical pressure and thermal energy generated by this technology result in material heating, melting, and sintering. This work investigates how the combination of ultrasound waves and a formulation comprising thermoplastic polyurethane (TPU) and low molecular weight polycaprolactone (L-PCL) influences the final properties of an implantable device designed for the sustained release of dipyridamole (DIP). The USAC-fabricated implants were thoroughly characterized to assess the material properties and the impact of the USAC technique. A comprehensive analysis was performed, including microscopy techniques such as Raman microscopy, acoustic microscopy, scanning electron microscopy (SEM), and optical coherence tomography (OCT), as well as X-ray Microcomputer Tomography (μCT). Additionally, thermal analysis, along with Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD), was performed to assess the interactions between the components and evaluate the crystallinity of the materials. Moreover, the mechanical properties and DIP release profiles of the implants were evaluated to study the feasibility of the USAC technique for manufacturing IDDS. The results suggested that the resulting materials were homogeneous, and non-covalent interactions between DIP and TPU were identified. These materials offered an attractive option for preparing TPU-based implantable devices due to their mechanical properties. Indeed, the addition of DIP in concentrations up to 20 % did not influence the compression modulus. In vitro release study demonstrated that the USAC-fabricated implants exhibited a sustained drug release profile throughout the 4-week study. Nevertheless, implants containing lower DIP loading exhibited a higher percentage release (6.29 %) compared to those with higher DIP loading (4.28 %), suggesting that the drug may be interacting with TPU within the USAC implantable devices, potentially limiting the release of DIP.
Enhanced Metabolic Syndrome Management Through Cannabidiol-Loaded PLGA Nanoparticles: Development and In Vitro Evaluation
(Wiley, 2025) El Hammadi, Mazen M.; Martín Navarro, Lucía; Berrocoso, Esther; Álvarez Fuentes, Josefa; Crespo Facorro, Benedicto; Suárez Pereira, Irene; Vázquez Bourgon, Javier; Martín Banderas, Lucía; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Instituto de Investigación Valdecilla (IDIVAL); Ministerio de Ciencia e Innovación (MICIN). España; Gobierno de España
Cannabidiol (CBD) holds promise for managing metabolic diseases, yet enhancing its oral bioavailability and efficacy remainschallenging. To address this, we developed polymeric nanoparticles (NPs), using poly(lactic-co-glycolic acid) (PLGA), encapsu-lating CBD using nanoprecipitation, aiming to create an effective CBD-nanoformulation for metabolic disorder treatment. TheseNPs (135–265 nm) demonstrated high encapsulation efficiency (EE% ≈ 100%) and sustained release kinetics. Their therapeuticpotential was evaluated in an in vitro metabolic syndrome model employing sodium palmitate-induced HepG2 cells. Key as-sessment parameters included cell viability (MTT assay), glucose uptake, lipid accumulation (Oil Red O staining), triglycerides,cholesterol, HDL-c levels, and gene expression of metabolic regulators. Results showed an IC50 of 9.85 μg/mL for free CBD
Effects of Combined CBGA and Cannabis-derived terpene nanoformulations on TRPV1 Activation: Implications for Enhanced Pain Management
(Elsevier, 2025) El Hammadi, Mazen M.; Small Howard, Andrea L.; Fernández Arévalo, María Mercedes; Turner, Helen; Martín Banderas, Lucía; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Universidad de Sevilla; National Institutes of Health (NIH)
Cannabinoids and terpenes, key bioactive components of cannabis, are increasingly studied for their individual and combined contributions to the therapeutic potential of cannabis-based treatments, with ongoing research exploring their distinct and interactive effects. This study aimed to encapsulate cannabigerolic acid (CBGA) in poly(ethylene glycol)-poly(lactic-co-glycolic acid) nanoparticles (PEG-PLGA NPs) and investigate the effects of combining CBGA NPs with cannabis-derived terpene-loaded NPs (myrcene [MC], nerolidol [NL], and caryophyllene [CPh]) for potential applications in pain management. CBGA NPs (152 nm) and terpene-loaded NPs (233–297 nm) were prepared via nanoprecipitation and emulsion-solvent evaporation, respectively, exhibiting a polydispersity index < 0.3 and negative zeta potentials (−23 to −26 mV). Encapsulation efficiency was 98.6 % for CBGA and 13–33 % for terpenes. CBGA release followed a biphasic profile, with ∼ 20 % released within 4 h and sustained release over 72 h. In vitro evaluation used HEK293 cells expressing the nociceptive transient receptor potential vanilloid-1 (TRPV1) channel, a key mediator of pain perception. TRPV1 activation was assessed via calcium influx kinetics (Fluo-4 indicator). The EC50 values were 23.8 µg/mL (CBGA NPs), 8.0 µg/mL (MC NPs), 6.7 µg/mL (NL NPs), and 13.3 µg/mL (CPh NPs). Combinatorial treatments of CBGA NPs with terpene NPs at their respective EC50 concentrations revealed significantly enhanced calcium influx compared to individual NPs, with the strongest interaction observed for CBGA/NL and moderate effects for CBGA/MC. Fluorescence imaging further corroborated these findings. These results suggest that combining CBGA NPs with terpene-loaded NPs could potentiate pain-relief efficacy, offering a promising strategy for advanced therapeutic formulations.
Reservoir-Type Subcutaneous Implantable DevicesContaining Porous Rate Controlling Membranes forSustained Delivery of Risperidone
(Wiley, 2025-01-16) Li, Linlin; Permana, Andi Dian; Domínguez Robles, Juan; Amir, Muh Nur; Habibie, Habibie; Anjani, Qonita Kurnia; Larrañeta, Eneko; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. España; European Union (UE); Ministerio de Ciencia e Innovación (MICIN). España
Implantable drug delivery systems are crucial for achieving sustained deliveryof active compounds to speciﬁc sites or systemic circulation. In this study, anovel reservoir-type implant combining a biodegradable rate-controllingmembrane with a drug-containing core prepared using direct compressiontechniques is developed. The membrane is composed of poly(caprolactone)(PCL), and risperidone (RIS) served as the model drug. Characterization ofboth membranes and direct compressed pellets includes hardness testing,optical coherence tomography, mercury intrusion porosimetry, and surfacemorphology observation. In vitro release studies of RIS reveal that higher drugloading in the pellets extended-release duration up to 70 days whenincorporated into membranes with four layers. Increasing the number ofmembrane layers slows the release rate further, ranging from 70 to 170 daysdepending on membrane thickness. Biocompatibility studies demonstratethat these implantable devices are non-toxic and biocompatible with cells invitro. In vivo studies conduct in male Wistar rats demonstrate sustainedrelease of RIS, with plasma levels showing a signiﬁcant increasepost-implantation at a relatively constant rate for up to 49 days. These resultsindicate that the developed implants have the potential to provide long-actingdrug delivery to the systemic circulation.
Curcumin-Loaded High-Charge Swelling Synthetic Mica: Characterization Studies and Stability under Stress Conditions
(American Chemical Society (ACS), 2025-05-23) Orta Cuevas, María del Mar; Fernández Romero, Ana María; Rabasco Álvarez, Antonio María; Medina Carrasco, Santiago; González Rodríguez, María Luisa; Universidad de Sevilla. Departamento de Química Analítica; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Universidad de Sevilla
Curcumin (Cur) is a bioactive compound with various pharmacotherapeutic effects. However, its limited solubility and stability pose challenges for therapeutic applications. Clay minerals, such as montmorillonite (MMT) and high-charge swelling synthetic micas, show promise as drug carriers due to their properties. This study aimed to obtain complexes with clay minerals that could enhance the stability of Cur. MMT, Na-Mica-4, and the latter organofunctionalized with 18-carbon alkylamines (C18-Mica-4) were used as support for Cur. Adsorption studies showed that Na-Mica-4 exhibited the highest percentage of adsorption (60%). Cur-Mica-4 complexes were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermal analysis (DSC and TGA), specific surface area (BET), pore size and volume determinations, and surface charge determination by zeta potential measurement. The effect of light on Cur and Cur-Mica-4 complexes was also evaluated. Forced degradation studies were performed under hydrolytic, oxidative, photolytic, and thermal conditions to assess the stability and degradation pathways. The FTIR spectra indicated that the enol tautomer mainly formed part of the complexes. BET analysis showed a reduced pore size after adsorption, indicating Cur immobilization. TGA and scanning electron microscopy (SEM) suggested degradation primarily occurring under exposure to sunlight, heat, and ultraviolet light. The effect of acidic and basic conditions on the Cur-Mica-4 complex was evaluated. Under acidic conditions, a decrease in the specific surface area of the complex was observed, suggesting the formation of larger configurational structures. An increase in the specific surface area with a smaller pore size was observed in the basic medium, possibly due to the formation of new structures in the clay minerals, supported by XRD results. These findings indicate that the pH of the medium can significantly influence the structure and stability of the Cur-Mica-4 complex, which could have important implications for its application in specific environments, such as drug delivery systems.
La regulación del establecimiento de las oficinas de farmacia y la planificación farmacéutica de las ordenanzas a la regulación autonómica
(2023-10) Leiva Bugella, Sara; González Lara, Francisco; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
Este trabajo reúne la normativa vinculada al establecimiento de las oficinas de farmacia, así como de la planificación farmacéutica española, haciendo un recorrido a lo largo de los años, hasta la normativa actual. El sector farmacéutico, pese a ser una actividad privada, siempre ha tenido una vital importancia en la salud pública, por lo que su control administrativo ha sido necesario, siendo de gran importancia la autorización administrativa de las oficinas de farmacia. Analizamos por ello la normativa que ha regido su establecimiento, desde las primeras ordenanzas dictadas para su control hasta la vigente normativa autonómica. Un largo recorrido de más de dos siglos, en los que la evolución de la profesión farmacéutica corre paralela a los cambios políticos y económicos que han transformado nuestro país.
Development of chitosan-clay nanocomposite films from Hermetia illucens: analysis of chemical, physical, and mechanical properties
(Elsevier, 2025-06) Ianniciello, Dolores; Peláez Montosa, Ada; Melo Barbosa, Raquel de; García Villén, Fátima; Salvia, Rosanna; Scieuzo, Carmen; Viseras, César; Falabella, Patrizia; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; European Union (UE); Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Italian Ministry of University and Research
Chitosan has gained great attention due to its properties. In this study, chitosan obtained from an innovative and sustainable source, the bioconverter insect Hermetia illucens, known as Black Soldier Fly (BSF), was used for the development of Chitosan-Clay Nanocomposite Films. Sepiolite and montmorillonite clays were used to produce the membranes. The interaction between insect-derived chitosan and clays was studied and the chemical, thermal, mechanical, and adhesive properties of the films were assessed. The incorporation of clays enhanced thermal stability and hydrophobicity of all formulations. Films prepared with chitosan from H. illucens exhibited greater hydrophobicity than those made with commercial chitosan, particularly in unbleached samples. However, chitosan from H. illucens displayed lower elasticity and tensile strength. Despite this, the addition of clays to pupal exuviae and adult unbleached samples resulted in mechanical properties comparable to commercial chitosan. Adhesive properties of BSF chitosan consistently outperformed commercial chitosan. Unbleached samples demonstrated better performance, suggesting that the bleaching process is unnecessary for film production. Based on the results obtained, insect chitosan could be particularly advantageous in applications requiring improved adhesiveness and enhanced thermal resistance and hydrophobicity, such as in wound dressings for exudative wounds.
La presencia de mujeres en los estudios de Farmacia de las universidades peninsulares españolas (1913-1936)
(Sociedad Española de Historia de las Ciencias y de las Técnicas (SEHCYT), 2022) González Bueno, Antonio; Nuñez Valdés, Juan; Ramos Carrillo, Antonio; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
La incorporación de las mujeres a la actividad farmacéutica corre paralela a su actividad social. En este artículo nos ocupamos de describir el proceso que llevó a las mujeres a cursar, en la España metropolitana, los estudios de la Licenciatura en Farmacia. Utilizando los Anuarios Estadísticos de España (Fondo documental del Instituto Nacional de Estadística) cuantificamos la presencia de mujeres entre los inicios de la década de 1910 y el comienzo de la Guerra Civil española (1936), constatando una línea claramente ascendente; el mítico 10% del alumnado femenino se supera, en lo que a los estudios de Farmacia respecta, en el curso 1922/23. Los porcentajes de alumnas matriculadas en las Facultades de Farmacia tienden a la estabilización en el gozne de las décadas de 1920 a 1930; en el curso 1932/33 este porcentaje femenino rozaba un 20% (19.95%). De acuerdo con los datos ofrecidos por los Anuarios Estadísticos de España, fue la Facultad de Farmacia de la Universidad Central la que recibió un mayor número de alumnas; sus valores más altos se alcanzan durante el curso 1928/29 (32.15%); las otras universidades hispanas donde podían cursarse los estudios de Farmacia: Barcelona, Santiago de Compostela y Granada, presenta valores significativamente más bajos que la Central.
Fibrosis Quística: tratamiento actual y avances con la nanotecnología
(Universidad de Granada, 2020) Guerra Morillo, María Oliva; Rabasco Álvarez, Antonio María; González Rodríguez, María Luisa; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
Introducción: Actualmente, los tratamientos existentes para tratar la fibrosis quística (FQ) están diseña-dos para controlar sus síntomas, consistentes principalmente en retención de moco e infección crónica. Se propone la vía pulmonar como alternativa para la administración de los fármacos, principalmente antimicrobianos. Sin embargo, su rápido aclaramiento, que conduce a niveles bajos de fármaco e incremento de los regímenes posológicos, así como la aparición de efectos adversos, hacen de la nanotecnología una estrategia interesante para esta enfermedad. Objetivo: estudiar y analizar los diferentes sistemas nanoparticulares existentes para su uso por vía pulmonar, concretando en el uso de sistemas lipídicos para el tratamiento de la FQ. Método: se realizó una búsqueda no sistemática de artículos en diferentes bases de datos, en los últimos 10 años principalmente, siguiendo pautas establecidas de palabras clave. Resultados: Los progresos que se han conseguido en los últimos años hacen que la FQ pase a ser una enfermedad de adultos. Los tratamientos que se están usando en la actualidad están siendo cada vez más desplazados por otras alternativas, como los sistemas nanoparticulares, siendo idóneos para la administración pulmonar debido a su pequeño tamaño, su liberación sostenida y su elevada biocompatibilidad. Entre éstos, destacan los liposomas por su similitud estructural con el surfactante pulmonar, así como por su capacidad de destruir las biopelículas bacterianas. La mayoría de las formulaciones encontradas contenían un solo fármaco. Conclusión: Existen evidencias científicas que indican que la investigación debe dirigirse hacia el desarrollo de formulaciones que sean capaces de destruir la biopelícula.
Generalidades sobre las vacunas comercializadas en España: estudio monográfico de la vacuna contra el sarampión
(Universidad de Granada, 2020) Mejías Padilla, Carmen; Ginés Dorado, Juan Manuel; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica
Introducción: la vacunación es, en la historia de la medicina, una de las actuaciones más significativas en la reducción de la mortalidad infantil y la erradicación de enfermedades. Sin embargo, con el apogeo de los denominados grupos “antivacunas” ha aumentado la incidencia de enfermedades infecciosas, entre ellas, el sarampión, cuya erradicación no ha sido posible para el año 2015, como había propuesto la Organización Mundial de la Salud. Objetivo: hemos estudiado diferentes aspectos tecnológicos de las vacunas comercializadas en España, centrándonos en las utilizadas contra el sarampión, y su problemática actual a la hora de su administración. Método: se ha realizado un estudio de las fichas técnicas de las vacunas recogidas en la Agencia Española de Medicamentos y Productos Sanitarios. Resultados: se obtuvieron resultados sobre diferentes aspectos: tipo de vacuna, sistema fisicoquímico, forma farmacéutica, vía de administración y dispositivo para su administración. Además, se han analizado las formulaciones de las vacunas existentes contra el sarampión, haciendo hincapié en los diversos excipientes que contienen: estabilizadores, antibióticos, medios de cultivo, etc. Conclusiones: la mayoría de las vacunas comercializadas en España se presentan en forma de suspensión para administración intramuscular o subcutánea mediante jeringa precargada. En el caso de la vacuna contra el sarampión, encontramos tres medicamentos de preparación extemporánea, que se presentan en forma de polvo liofilizado en vial y vehículo en jeringa precargada, producidas a partir de diferentes virus vivos o atenuados, siendo por tanto vacunas combinadas
Development of Axitinib-loaded Polymeric Ocular Implants for the Treatment of Posterior Ocular Diseases
(Elsevier, 2025) Annuryanti, Febri; Adhami, Masoud; Abdi, Ubah; Domínguez Robles, Juan; Larrañeta, Eneko; Vora, Lalitkumar K.; Raghu Raj Singh, Thakur; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Wellcome Trust; Ministerio de Ciencia e Innovación (MICIN). España
Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are the primary causes of vision impairment and blindness worldwide. The current treatment for these diseases is an intravitreal injection of anti-VEGF agents, which are costly and require frequent injections. Implants can be used to sustain the release of drugs and minimize side effects. Axitinib (AX) is a potent VEGF receptor inhibitor and a promising candidate for treating posterior ocular diseases, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). A sustained release of AX was successfully achieved from 3D-printed AX-loaded implants fabricated using the well-known 3D printing technique, semi-solid extrusion (SSE). AX at concentrations of 10% w/w and 20% w/w was incorporated within the polycaprolactone (PCL) and Precirol®-based matrix. The fabricated implants were characterized via FTIR spectroscopy, SEM imaging, and thermal analysis. The implants were also evaluated for their drug release and biocompatibility. The AX-loaded implants exhibited thermal stability, and no chemical interactions were found between AX and the matrix components. The release mechanism study of AX revealed that the concentration of drug loading influenced AX release from the implant, with a 10% w/w and 20 %w/w of AX showing first-order and Korsmeyer-Peppas mechanism, respectively. A biocompatibility study using ARPE-19 cells confirmed that AX-loaded implants are nontoxic and safe for ocular use.
Bioinspired Orthogonal-shaped protein–biometal Nanocrystals Enable Oral Protein Absorption
(Elsevier, 2025) Durán Lobato, María Matilde; Tovar, Sulay; Cuñarro, Juan; Ramos Membrive, Rocío; Peñuelas, Iván; Marigo, Ilaria; Benetti, Federico; Chenlo, Miguel; Álvarez, Clara V.; Ildikó, Vashegyi; Alonso, María José; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; European Union (UE); Ministerio de Ciencia e Innovación (MICIN). España
With the growing number of marketed biological drugs, the development of technological strategies for their oral systemic absorption, becomes increasingly important. The harsh gastrointestinal environment and low permeability of the intestinal epithelium, represent a huge challenge for their systemic delivery. Herein, bioinspired in the physiological insulin-Zn interaction, the design of orthogonal-shaped protein-biometal hybrid nanocrystals, further enveloped by a bilayer of functional biomaterials, is reported. The nanocrystals exhibited a size of 80 nm, a neutral surface charge and a high insulin loading. In vitro studies showed the capacity of the nanocomplexes to control the release of the associated insulin, while preserving its stability. In vivo evaluation showed sustained blood glucose reductions in both healthy and diabetic rats (up to 40 % and 80 %, respectively), while chronic immunotoxicity studies in mice indicated no toxicity effect. Preliminary efficacy studies in healthy awake pigs following oral capsule administration showed over 20 % absolute bioavailability.
Starch-Based scaffold produced by FDM 3D printing technique as Innovative and biosustainable wound dressing
(Elsevier, 2025-05) Dominici, Franco; Imbriano, Anna; Puglia, Debora; Pagano, Cinzia; Luzi, Francesca; Rafanelli, Aurora; Michele, Alessandro Di; Bonacci, Francesco; Melo Barbosa, Raquel de; Perioli, Luana; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Italian Ministry of University and Research (MUR); Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Junta de Andalucía
Starch is a safe biopolymer, whose use for the production of scaffolds intended for deep wounds treatment is limited, due to its low mechanical and thermal properties. For this reason, until now, it has been used in low amounts and/or in combination with other biopolymers. The aim of the study was to produce thermoplastic filaments (TPS) with high starch content, useful for scaffolds production by Fusion Deposition Modelling 3D printing technique. TPS was obtained by hot melt extrusion from a mixture of starch (70 % w/w) and glycerol (30 % w/w) combined to cationic clay montmorillonite, citric acid and magnesium stearate to improve strength and processability. The prepared scaffold was characterized and compared to other two scaffolds, where the effect of the addition of polycaprolactone (PCL) or methylsulphonylmethane (MSM) (as thermostable model drug) to the blend was evaluated. The mechanical properties were investigated by Brillouin Light Scattering. In vitro studies highlighted that the scaffolds are: i) able to absorb simulated exudates (reaching a hydration of 35 % in 7 days); ii) safe on keratinocytes (viability > 70 %) stimulating their growth; iii) able to inhibit S. pyogenes growth.
Optimising 3D printed medications for rare diseases: In-line mass uniformity testing in direct powder extrusion 3D printing
(Elsevier, 2025) Mora Castaño, Gloria; Rodríguez Pombo, Lucía; Carou-Senra, Paola; Januskaite, Patricija; Rial, Carlos; Bendicho-Lavilla, Carlos; Couce, Maria L.; Millán Jiménez, Mónica; Caraballo Rodríguez, Isidoro; Basit, Abdul W.; Alvarez-Lorenzo, Carmen; Goyanes, Alvaro; Universidad de Sevilla. Departamento de Farmacia y Tecnología Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Xunta de Galicia; Fundación Mutua Madrileña; Engineering and Physical Sciences Research Council (EPSRC)
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.

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