Person:
Andrés Guerrero, Vanesa

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First Name
Vanesa
Last Name
Andrés Guerrero
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Farmacia Galénica y Tecnología Alimentaria
Area
Farmacia y Tecnología Farmaceútica
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Search Results

Now showing 1 - 10 of 13
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    Dexamethasone PLGA Microspheres for Sub-Tenon Administration: Influence of Sterilization and Tolerance Studies
    (Pharmaceutics, 2021) Barbosa Alfaro, Deyanira; Andrés Guerrero, Vanesa; Fernández Bueno, Iván; García Gutiérrez, María Teresa; Gil Alegre, María Esther; Molina Martínez, Irene Teresa; Pastor Jimeno, José Carlos; Herrero Vanrell, María Del Rocío; Bravo Osuna, Irene
    Many diseases affecting the posterior segment of the eye require repeated intravitreal injections with corticosteroids in chronic treatments. The periocular administration is a less invasive route attracting considerable attention for long-term therapies. In the present work, dexamethasone-loaded poly(lactic-co-glycolic) acid (PLGA) microspheres (Dx-MS) were prepared using the oil-in-water (O/W) emulsion solvent evaporation technique. MS were characterized in terms of mean particle size and particle size distribution, external morphology, polymer integrity, drug content, and in vitro release profiles. MS were sterilized by gamma irradiation (25 kGy), and dexamethasone release profiles from sterilized and non-sterilized microspheres were compared by means of the similarity factor (f2). The mechanism of drug release before and after irradiation exposure of Dx-MS was identified using appropriate mathematical models. Dexamethasone release was sustained in vitro for 9 weeks. The evaluation of the in vivo tolerance was carried out in rabbit eyes, which received a sub-Tenon injection of 5 mg of sterilized Dx-MS (20–53 µm size containing 165.6 ± 3.6 µg Dx/mg MS) equivalent to 828 µg of Dx. No detectable increase in intraocular pressure was reported, and clinical and histological analysis of the ocular tissues showed no adverse events up to 6 weeks after the administration. According to the data presented in this work, the sub-Tenon administration of Dx-MS could be a promising alternative to successive intravitreal injections for the treatment of chronic diseases of the back of the eye.
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    Smart biodegradable hydrogels: Drug-delivery platforms for treatment of chronic ophthalmic diseases affecting the back of the eye
    (International Journal of Pharmaceutics, 2024) Aragón Navas, Alba; López-Cano, José Javier; Johnson, Melissa; A, Sigen; Vicario De La Torre, Marta; Andrés Guerrero, Vanesa; Tai, Hongyun; Wang, Wenxin; Bravo Osuna, Irene; Herrero Vanrell, María Del Rocío
    This paper aims to develop smart hydrogels based on functionalized hyaluronic acid (HA) and PLGA-PEG-PLGA (PLGA,poly-(DL-lactic-co-glycolic acid); PEG,polyethylene glycol) for use as intraocular drug-delivery platforms. Anti-inflammatory agent dexamethasone-phosphate (0.2 %w/v) was the drug selected to load on the hydrogels. Initially, different ratios of HA-aldehyde (HA-CHO) and thiolated-HA (HA-SH) were assayed, selecting as optimal concentrations 2 and 3 % (w/v), respectively. Optimized HA hydrogel formulations presented fast degradation (8 days) and drug release (91.46 ± 3.80 % in 24 h), thus being suitable for short-term intravitreal treatments. Different technology-based strategies were adopted to accelerate PLGA-PEG-PLGA water solubility, e.g. substituting PEG1500 in synthesis for higher molecular weight PEG3000 or adding cryopreserving substances to the buffer dissolution. PEG1500 was chosen to continue optimization and the final PLGA-PEG-PLGA hydrogels (PPP1500) were dissolved in trehalose or mannitol carbonate buffer. These presented more sustained release (71.77 ± 1.59 % and 73.41 ± 0.83 % in 24 h, respectively) and slower degradation (>14 days). In vitro cytotoxicity studies in the retinal-pigmented epithelial cell line (RPE-1) demonstrated good tolerance (viability values > 90 %). PLGA-PEG-PLGA hydrogels are proposed as suitable candidates for long-term intravitreal treatments. Preliminary wound healing studies with PLGA-PEG-PLGA hydrogels suggested faster proliferation at 8 h than controls.
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    Enhancing the hypotensive effect of latanoprost by combining synthetic phosphatidylcholine liposomes with hyaluronic acid and osmoprotective agents
    (Drug Delivery and Translational Research, 2024) Brugnera, Marco; Vicario De La Torre, Marta; González-Cela Casamayor, Miriam Ana; López Cano, José Javier; Bravo Osuna, Irene; Huete Toral, Fernando; González Rubio, María Luisa; Carracedo Rodríguez, Juan Gonzalo; Molina Martínez, Irene Teresa; Andrés Guerrero, Vanesa; Herrero Vanrell, María Del Rocío
    The first line of glaucoma treatment focuses on reducing intraocular pressure (IOP) through the prescription of topical prostaglandin analogues, such as latanoprost (LAT). Topical ophthalmic medicines have low bioavailability due to their rapid elimination from the ocular surface. Nanotechnology offers innovative ways of enhancing the ocular bioavailability of antiglaucoma agents while reducing administration frequency. This study aims to combine LAT-loaded synthetic phosphatidylcholine liposomes with hyaluronic acid (0.2% w/v) and the osmoprotectants betaine (0.40% w/v) and leucine (0.90% w/v) (LAT-HA-LIP) to extend the hypotensive effect of LAT while protecting the ocular surface. LAT-HA-LIP was prepared as a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phosphocholine, cholesterol and α-tocopherol acetate. LAT-HA-LIP exhibited high drug-loading capacity (104.52 ± 4.10%), unimodal vesicle sizes (195.14 ± 14.34 nm) and a zeta potential of -13.96 ± 0.78 mV. LAT-HA-LIP was isotonic (284.00 ± 1.41 mOsm L-1), had neutral pH (7.63 ± 0.01) and had suitable surface tension (44.07 ± 2.70 mN m-1) and viscosity (2.69 ± 0.15 mPa s-1) for topical ophthalmic administration. LAT-HA-LIP exhibited optimal in vitro tolerance in human corneal and conjunctival epithelial cells. No signs of ocular alteration or discomfort were observed when LAT-HA-LIP was instilled in albino male New Zealand rabbits. Hypotensive studies revealed that, after a single eye drop, the effect of LAT-HA-LIP lasted 24 h longer than that of a marketed formulation and that relative ocular bioavailability was almost three times higher (p < 0.001). These findings indicate the potential ocular protection and hypotensive effect LAT-HA-LIP offers in glaucoma treatment.
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    Project number: 372
    Resiliencia y adaptabilidad en Farmacia: Aprovechamiento de la experiencia de enseñanza-aprendizaje en tiempos de pandemia por CoVid19 aplicando B-Learning y learning analytics
    (2022) Notario Pérez, Fernando; Ruiz Caro, Roberto; Veiga Ochoa, María Dolores; Molina Martínez, Irene Teresa; Herrero Vanrell, María Del Rocío; Bravo Osuna, Irene; Vicario De La Torre, Marta; Martin Erdocia, Izaskun; Cazorla Luna, Raúl; García Herranz, David; López Cano, José Javier; Martín Illana, Araceli; Gil Alegre, María Esther; Andrés Guerrero, Vanesa; Aragón Navas, Alba
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    Proinflammatory cytokine profile differences between primary open angle and pseudoexfoliative glaucoma
    (Ophthalmic Research, 2021) Vidal Villegas, Beatriz; Burgos Blasco, Bárbara; Santiago Álvarez, Jose Luis; Espino Paisán, Laura; Fernández Vigo, José Ignacio; Andrés Guerrero, Vanesa; García Feijoo, Julián; Martínez De La Casa Fernández-Borrella, José María
    Introduction: Few studies have investigated glaucoma biomarkers in aqueous humor and tear and have found elevations of proinflammatory cytokines in patients with primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PXG). In this study we investigate differences in inflammatory cytokines between POAG and PXG patients to find specific disease biomarkers. Methods: For this purpose, tear and aqueous humor samples of 14 eyes with POAG and 15 eyes with PXG undergoing cataract surgery were immunoassayed for 27 pro-inflammatory cytokines. The concentrations of cytokines in tear and aqueous humor and their association with clinical variables were analysed, correlated and compared between the groups. Results: We found that the levels of three cytokines differed significantly in the aqueous humor of POAG and PXG patients: IL-12 and IL-13 were higher in the POAG group, while MCP-1(MCAF) was higher in the PXG group. The number of topical hypotensive medications was correlated with diminished levels of two cytokines (IL-7 and basic fibroblast growth factor) in aqueous humor in the POAG group and with diminished levels of IL-12 in tear in the PXG group. Conclusion: We conclude that both POAG and PXG show elevated concentrations of proinflammatory cytokines in tear and aqueous humor that could be used as biomarkers for these types of glaucoma and that the concentrations in aqueous humor of three cytokines: IL-12, IL-13 and MCP-1(MCAF) could be used to differentiate POAG and PXG.
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    Enhancing the hypotensive effect of latanoprost by combining synthetic phosphatidylcholine liposomes with hyaluronic acid and osmoprotective agents
    (Drug Delivery and Translational Research, 2024) Brugnera, Marco; Vicario De La Torre, Marta; González-Cela Casamayor, Miriam Ana; López Cano, José Javier; Bravo Osuna, Irene; Huete Toral, Fernando; González Rubio, María Luisa; Carracedo Rodríguez, Juan Gonzalo; Molina Martínez, Irene Teresa; Andrés Guerrero, Vanesa; Herrero Vanrell, María Del Rocío
    The first line of glaucoma treatment focuses on reducing intraocular pressure (IOP) through the prescription of topical prostaglandin analogues, such as latanoprost (LAT). Topical ophthalmic medicines have low bioavailability due to their rapid elimination from the ocular surface. Nanotechnology offers innovative ways of enhancing the ocular bioavailability of antiglaucoma agents while reducing administration frequency. This study aims to combine LAT-loaded synthetic phosphatidylcholine liposomes with hyaluronic acid (0.2% w/v) and the osmoprotectants betaine (0.40% w/v) and leucine (0.90% w/v) (LAT-HA-LIP) to extend the hypotensive effect of LAT while protecting the ocular surface. LAT-HA-LIP was prepared as a mixture of 1,2-dioleoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-glycero-3-phosphocholine, cholesterol and α-tocopherol acetate. LAT-HA-LIP exhibited high drug-loading capacity (104.52 ± 4.10%), unimodal vesicle sizes (195.14 ± 14.34 nm) and a zeta potential of -13.96 ± 0.78 mV. LAT-HA-LIP was isotonic (284.00 ± 1.41 mOsm L−1), had neutral pH (7.63 ± 0.01) and had suitable surface tension (44.07 ± 2.70 mN m−1) and viscosity (2.69 ± 0.15 mPa s−1) for topical ophthalmic administration. LAT-HA-LIP exhibited optimal in vitro tolerance in human corneal and conjunctival epithelial cells. No signs of ocular alteration or discomfort were observed when LAT-HA-LIP was instilled in albino male New Zealand rabbits. Hypotensive studies revealed that, after a single eye drop, the effect of LAT-HA-LIP lasted 24 h longer than that of a marketed formulation and that relative ocular bioavailability was almost three times higher (p < 0.001). These findings indicate the potential ocular protection and hypotensive effect LAT-HA-LIP offers in glaucoma treatment.
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    Novel Osmoprotective DOPC-DMPC Liposomes Loaded with Antihypertensive Drugs as Potential Strategy for Glaucoma Treatment
    (Pharmaceutics, 2022) González-Cela Casamayor, Miriam Ana; López Cano, José Javier; Bravo Osuna, Irene; Andrés Guerrero, Vanesa; Vicario De La Torre, Marta; Guzmán Navarro, Manuel; Benítez Del Castillo Sánchez, José Manuel; Herrero Vanrell, María Del Rocío; Molina Martínez, Irene Teresa
    Glaucoma is a group of chronic irreversible neuropathies that affect the retina and the optic nerve. It is considered one of the leading causes of blindness in the world. Although it can be due to various causes, the most important modifiable risk factor is the elevated intraocular pressure (IOP). In this case, the treatment of choice consists of instilling antihypertensive formulations on the ocular surface. The chronicity of the pathology, together with the low bioavailability of the drugs that are applied on the ocular surface, make it necessary to instill the formulations very frequently, which is associated, in many cases, with the appearance of dry eye disease (DED). The objective of this work is the design of topical ocular formulations capable of treating glaucoma and, at the same time, preventing DED. For this, two liposome formulations, loaded with brimonidine or with travoprost, were Tadeveloped using synthetic phospholipids and enriched by the addition of compounds with osmoprotective activity. The proposed formulations not only presented physicochemical characteristics (size, pH, osmolarity, surface tension, and viscosity) and encapsulation efficiency values (EE% of 24.78% and ≥99.01% for brimonidine and travoprost, respectively) suitable for ocular surface administration, but also showed good tolerance in human corneal and conjunctival cell cultures, as well as an in vitro osmoprotective activity. The hypotensive effect of both liposomal formulations was evaluated in normotensive albino New Zealand rabbits, showing a faster and longer lasting reduction of intraocular pressure in comparison to the corresponding commercialized products used as control. According to these results, the hypotensive liposomal formulations combined with osmoprotective agents would result in a very promising platform for the treatment of glaucoma and the simultaneous protection of the ocular surface.
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    Combined hyperosmolarity and inflammatory conditions in stressed human corneal epithelial cells and macrophages to evaluate osmoprotective agents as potential DED treatments
    (Experimental Eye Research, 2021) López Cano, José Javier; González-Cela Casamayor, Miriam Ana; Andrés Guerrero, Vanesa; Herrero Vanrell, María Del Rocío; Benítez Del Castillo Sánchez, José Manuel; Molina Martínez, Irene Teresa
    Purpose: To develop an easy-to-perform combined model in human corneal epithelial cells (HCECs) and Balb/c mice macrophages J774.A1 (MP) for preliminary screening of potential ophthalmic therapeutic substances. Methods: HCECs were exposed to different osmolarities (350–500 mOsm/L) and MTT assay was employed for cell survival and flow cytometry to assess apoptosis-necrosis and relative cell size (RCS) distribution. Effectiveness of Betaine, L-Carnitine, Taurine at different concentrations (ranging from 20 mM to 200 mM) was studied. Also, mucoadhesive polymers such as Hyaluronic acid (HA) and Hydroxypropylmethylcellulose (HPMC) (0.4 and 0.8%) were evaluated. Cells were pre-incubated with the compounds (8h) and then exposed to hyperosmotic stress (470 mOsm/L) for 16h. Moreover, anti-inflammatory activity was performed in LPS-stimulated MP. Results: Exposure to hyperosmotic solutions between 450 and 500 mOsm/L promoted the highest cell death after 16h exposures (p < 0.0001) with a drop in viability to 34.96% ± 11.77 for 470 mOsm/L. Pre-incubation with Betaine at 150 mM and 200 mM provided the highest cell survival against hyperosmolarity (66.01% ± 3.65 and 65.90% ± 0.78 respectively) while HA 0.4% was the most effective polymer in preventing cell death (42.2% ± 3.60). Flow cytometry showed that Betaine and Taurine at concentrations between 150-200 mM and 20–80 mM respectively presented the highest anti-apoptotic activity. Also, HA and HPMC polymers reduced apoptoticinduced cell death. All osmoprotectants modified RCS, and polymers increased their value over 100%. LCarnitine 50 mM, Taurine 40 mM and HA 0.4% presented the highest TNF-α inhibition activity (60%) albeit all of them showed anti-inflammatory inhibition percentages higher than 20%. Conclusions: HCECs hyperosmolar model combined with inflammatory conditions in macrophages allows the screening of osmoprotectants by simulating chronic hyperosmolarity (16h) and inflammation (24h).
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    Thermo-Responsive PLGA-PEG-PLGA Hydrogels as Novel Injectable Platforms for Neuroprotective Combined Therapies in the Treatment of Retinal Degenerative Diseases
    (Pharmaceutics, 2021) López Cano, José Javier; A, Sigen; Andrés Guerrero, Vanesa; Tai, Hongyun; Bravo Osuna, Irene; Molina Martínez, Irene Teresa; Wang, Wenxin; Herrero Vanrell, María Del Rocío
    The present study aims to develop a thermo-responsive-injectable hydrogel (HyG) based on PLGA-PEG-PLGA (PLGA = poly-(DL-lactic acid co-glycolic acid); PEG = polyethylene glycol) to deliver neuroprotective agents to the retina over time. Two PLGA-PEG PLGA copolymers with different PEG:LA:GA ratios (1:1.54:23.1 and 1:2.25:22.5) for HyG-1 and HyG-2 development respectively were synthetized and characterized by different techniques (gel permeation chromatography (GPC), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), critical micelle concentration (CMC), gelation and rheological behaviour). According to the physicochemical characterization, HyG-1 was selected for further studies and loaded with anti-inflammatory drugs: dexamethasone (0.2%), and ketorolac (0.5%), alone or in combination with the antioxidants idebenone (1 µM) and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) (0.002%). In vitro drug release and cytotoxicity studies were performed for the active substances and hydrogels (loaded and drug-free). A cellular model based on oxidative stress was optimized for anti-inflammatory and antioxidant screening of the formulations by using retinal-pigmented epithelial cell line hTERT (RPE-1). The copolymer 1, used to prepare thermo-responsive HyG-1, showed low polydispersity (PDI = 1.22) and a strong gel behaviour at 25% (w/v) in an isotonic buffer solution close to the vitreous temperature (31–34 °C). Sustained release of dexamethasone and ketorolac was achieved between 47 and 62 days, depending on the composition. HyG-1 was well tolerated (84.5 ± 3.2%) in retinal cells, with values near 100% when the anti-inflammatory and antioxidant agents were included. The combination of idebenone and dexamethasone promoted high oxidative protection in the cells exposed to H2O2, with viability values of 86.2 ± 14.7%. Ketorolac and dexamethasone-based formulations ameliorated the production of TNF-α, showing significant results (p ≤ 0.0001). The hydrogels developed in the present study entail a novel biodegradable tool to treat neurodegenerative processes of the retina overtime
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    Project number: 416
    Convertir las adversidades en oportunidades: Propuesta de digitalización y sostenibilidad de aplicación a la modalidad de enseñanza presencial en Farmacia
    (2023) Andrés Guerrero, Vanesa; Herrero Vanrell, María Del Rocío; Gil Alegre, María Esther; Bravo Osuna, Irene; Ruiz Caro, Roberto; Vicario De La Torre, Marta; Notario Pérez, Fernando; Martín Erdocia, Izaskun; Aragón Navas, Alba; Brugnera, Marco; García Herranz, David; González-Cela Casamayor, Miriam Ana; López Cano, José Javier
    Mientras que la resiliencia es la capacidad de poder hacer frente a circunstancias inesperadas, superar las barreras y obstáculos y recuperarse después de los contratiempos, también implica aprender de esos contratiempos, para afrontarlos mejor la próxima vez. Por otro lado, la adaptabilidad es estar dispuesto y ser capaz de ajustarse a las condiciones cambiantes, notar esos cambios y encontrar nuevos enfoques y alternativas para responder a esos cambios. Analizar las experiencias adaptativas de los estudiantes y profesores de la asignatura de Tecnología Farmacéutica durante la pandemia con el fin de proponer mejoras de cara al futuro para mantener y mejorar la enseñanza si de nuevo se tuviera que impartir 100% online. Comparación de los resultados de varias encuestas realizadas por el Vicerrectorado de Calidad de la UCM y los profesores de Tecnología Farmacéutica a los alumnos, contrastando esa información con la encuesta realizada a los profesores de esa asignatura y los resultados cuantitativos calculados en tasas de éxito llevados a cabo por el Vicedecanato de Calidad de la Facultad de Farmacia. A pesar de que entre las respuestas realizadas por los alumnos a las encuestas en escala de Likert se mejora levemente el nivel de satisfacción con el profesorado en pandemia mediante enseñanza online, manteniéndose la tasa de éxito de alumnos que superan la asignatura respecto a otros cursos pre-pandemia, tanto alumnos como profesores en varias cuestiones, con respuestas abiertas o cerradas, además de valorar positivamente la experiencia, plantean algunas mejoras asumibles para el futuro, tanto a nivel de impartición de clases, evaluación y mayor y mejor uso de herramientas virtuales. Por ello, podemos concluir que aunque estudiantes, profesores y la calidad de la enseñanza se adaptaron virtualmente durante la pandemia, es posible mejorar algunos aspectos de cara a una situación futura similar.