Person: Herrero Vanrell, María Del Rocío
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First Name
María Del Rocío
Last Name
Herrero Vanrell
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Farmacia Galénica y Tecnología Alimentaria
Area
Farmacia y Tecnología Farmaceútica
Identifiers
37 results
Search Results
Now showing 1 - 10 of 37
Item 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, IreneMany 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.Item Optimising the controlled release of dexamethasone from a new generation of PLGA-based microspheres intended for intravitreal administration(European Journal of Pharmaceutical Sciences, 2016) Rodríguez Villanueva, Javier; Bravo Osuna, Irene; Herrero Vanrell, María Del Rocío; Molina Martínez, Irene Teresa; Guzmán Navarro, M.Successful therapy for chronic diseases affecting the posterior segment of the eye requires sustained drug concentrations at the site of action for extended periods of time. To achieve this, it is necessary to use high systemic doses or frequent intraocular injections, both associated with serious adverse effects. In order to avoid these complications and improve patient`s quality of life, an experimental study has been conducted on the preparation of a new generation of biodegradable poly D-L(lactide-co-glycolide (50:50) (PLGA) polymer microspheres (MSs) loaded with Dxm, vitamin E and/or human serum albumin (HSA). Particles were prepared according to a S/O/W encapsulation method and the 20-40μm fraction was selected. This narrow size distribution is suitable for minimally invasive intravitreal injection by small calibre needles. Characterisation of the MSs showed high Dxm loading and encapsulation efficiency (> 90%) without a strong interaction with the polymer matrix, as revealed by DSC analysis. MSs drug release studies indicated a small burst effect (lower than 5%) during the first five hours and subsequently, drug release was sustained for at least 30 days, led by diffusion and erosion mechanisms. Dxm release rate was modulated when solid state HSA was incorporated into MSs formulation. SDS-PAGE analysis showed that the protein maintained its integrity during the encapsulation process, as well as for the release study. MSs presented good tolerance and lack of cytotoxicity in macrophages and HeLa cultured cells. After 12 months of storage under standard refrigerated conditions (41ºC), MSs retained appropriate physical and chemical properties and analogous drug release kinetics. Therefore, we conclude that these microspheres are promising pharmaceutical systems for intraocular administration, allowing controlled release of the drug.- Project number: 215
Item Diseño de herramientas para la adquisición de competencias transversales CT9, CT11, CT12 y CT13 que fomenten el desarrollo de habilidades de aplicación en la formación y competencia laboral de alumnos del Grado en Farmacia(2018) Gil Alegre, María Esther; Molina Martínez, Irene Teresa; Pastoriza Abal, María Pilar; Herrero Vanrell, María Del Rocío; Bravo Osuna, Irene; Ruiz Caro, Roberto; Arranz Romera, AliciaA través de las competencias transversales comunes al Grado en Farmacia y a la materia Tecnología Farmacéutica se pretende dotar a los alumnos de herramientas para el desarrollo de habilidades necesarias en sus estudios y en su empleabilidad. Item Microspheres as intraocular therapeutic tools in chronic diseases of the optic nerve and retina(Advanced Drug Delivery Reviews, 2018) Bravo Osuna, Irene; Andrés-Guerrero, Vanessa; Arranz Romera, Alicia; Esteban Pérez, Sergio; Molina Martínez, Irene Teresa; Herrero Vanrell, María Del RocíoPathologies affecting the optic nerve and the retina are one of the major causes of blindness. These diseases include age-related macular degeneration (AMD), diabetic Retinopathy (DR) and glaucoma, among others. Also, there are genetic disorders that affect the retina causing visual impairment. The prevalence of neurodegenerative diseases of the posterior segment are increased as most of them are related with the elderly. Even with the access to different treatments, there are some challenges in managing patients suffering retinal diseases. One of them is the need for frequent interventions. Also, an unpredictable response to therapy has suggested that different pathways may be playing a role in the development of these diseases. The management of these pathologies requires the development of controlled drug delivery systems able to slow the progression of the disease without the need of frequent invasive interventions, typically related with endophthalmitis, retinal detachment, ocular hypertension, cataract, inflammation, and floaters, among other. Biodegradable microspheres are able to encapsulate low molecular weight substances and large molecules such as biotechnological products. Over the last years, a large variety of active substances has been encapsulated in microspheres with the intention of providing neuroprotection of the optic nerve and the retina. The purpose of the present review is to describe the use of microspheres in chronic neurodegenerative diseases affecting the retina and the optic nerve. The advantage of microencapsulation of low molecular weight drugs as well as therapeutic peptides and proteins to be used as neuroprotective strategy is discussed. Also, a new use of the microspheres in the development of animal models of neurodegeneration of the posterior segment is described.Item Pharmaceuticalmicroscale and nanoscale approaches for efficient treatment of ocular diseases(Drug Delivery and Translational Research, 2016) Bravo Osuna, Irene; Andrés Guerrero, Vanesa; Pastoriza Abal, María Pilar; Molina Martínez, Irene Teresa; Herrero Vanrell, María Del RocíoEfficient treatment of ocular diseases can be achieved thanks to the proper use of ophthalmic formulations based on emerging pharmaceutical approaches. Among them, microtechnology and nanotechnology strategies are of great interest in the development of novel drug delivery systems to be used for ocular therapy. The location of the target site in the eye as well as the ophthalmic disease will determine the route of administration (topical, intraocular, periocular, and suprachoroidal administration) and the most adequate device. In this review, we discuss the use of colloidal pharmaceutical systems (nanoparticles, liposomes, niosomes, dendrimers, and microemulsions), microparticles (microcapsules and microspheres), and hybrid systems (combination of different strategies) in the treatment of ophthalmic diseases. Emphasis has been placed in the therapeutic significance of each drug delivery system for clinical translation.Item Gelatin Nanoparticles-HPMC Hybrid System for Effective Ocular Topical Administration of Antihypertensive Agents(Pharmaceutics, 2020) Esteban Pérez, Sergio; Andrés-Guerrero, Vanessa; López Cano, José Javier; Molina Martínez, Irene Teresa; Herrero Vanrell, María Del Rocío; Bravo Osuna, IreneThe increment in ocular drug bioavailability after topical administration is one of the main challenges in pharmaceutical technology. For several years, different strategies based on nanotechnology, hydrogels or implants have been evaluated. Nowadays, the tolerance of ophthalmic preparations has become a critical issue and it is essential to the use of well tolerated excipients. In the present work, we have explored the potential of gelatin nanoparticles (GNPs) loaded with timolol maleate (TM), a beta-adrenergic blocker widely used in the clinic for glaucoma treatment and a hybrid system of TM-GNPs included in a hydroxypropyl methylcellulose (HPMC) viscous solution. The TM- loaded nanoparticles (mean particle size of 193 ± 20 nm and drug loading of 0.291 ± 0.019 mg TM/mg GNPs) were well tolerated both in vitro (human corneal cells) and in vivo. The in vivo efficacy studies performed in normotensive rabbits demonstrated that these gelatin nanoparticles were able to achieve the same hypotensive effect as a marketed formulation (0.5% TM) containing a 5-fold lower concentration of the drug. When comparing commercial and TM GNPs formulations with the same TM dose, nanoparticles generated an increased efficacy with a significant (p < 0.05) reduction of intraocular pressure (IOP) (from 21% to 30%) and an augmentation of 1.7-fold in the area under the curve (AUC)(0–12h). On the other hand, the combination of timolol-loaded nanoparticles (TM 0.1%) and the viscous polymer HPMC 0.3%, statistically improved the IOP reduction up to 30% (4.65 mmHg) accompanied by a faster time of maximum effect (tmax = 1 h). Furthermore, the hypotensive effect was extended for four additional hours, reaching a pharmacological activity that lasted 12 h after a single instillation of this combination, and leading to an AUC(0 12h) 2.5-fold higher than the one observed for the marketed formulation. According to the data presented in this work, the use of hybrid systems that combine well tolerated gelatin nanoparticles and a viscous agent could be a promising alternative in the management of high intraocular pressure in glaucoma.Item CHAPTER 10: Drug Delivery Systems for the Treatment of Diseases Affecting the Retina and Optic Nerve.(Therapies for Retinal Degeneration: Targeting Common Processes, 2018) Bravo Osuna, Irene; Andrés Guerrero, Vanesa; Molina Martínez, Irene Teresa; Herrero Vanrell, María Del Rocío; De la Rosa, Enrique J.; Cotter, Thomas G.Diseases affecting the retina and the optic nerve are the major causes of irreversible blindness in the elderly population. Succesful therapy of these pathologies requires frequent administration of the active molecule close to the retinal target site. Intraocular drug delivery systems (IDDS) are emerging therapeutic tools in the treatment of diseases affecting the posterior segment, as they are able to provide effective concentrations of the drug for a long period, thus avoiding successive injections. Depending on their size, IDDS are classified in implants, microsystems and nanosystems. This chapter covers a general description of the IDDS useful for the treatment of diseases affecting retinal structures. © The Royal Society of Chemistry 2019.Item Nano and microtechnologies for ophthalmic administration. An overview(Journal of Drug Delivery Science and Technology, 2013) Herrero Vanrell, María Del Rocío; Vicario De La Torre, Marta; Andrés-Guerrero, Vanessa; Barbosa-Alfaro, Deyanira; Molina Martínez, Irene Teresa; Bravo Osuna, IreneOcular drug delivery is one of the most challenging fields of pharmaceutical research. They are generally employed to overcome the static (different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers) and dynamic barriers (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution) of the eye. Ophthalmic formulations must be sterile, and the biomaterials used in the preparation of pharmaceutical systems completely compatible and extremely well tolerated by ocular tissues. The location of the target tissue in the eye will determine the route of administration. Ophthalmic administration systems are intended for topical, intraocular and periocular administration. In this review we describe the main pharmaceutical nano- and microsystems currently under study to administrate drugs in the eye, covering microparticles, nanoparticles, liposomes, microemulsions, niosomes and dendrimers. We have performed the corresponding revision of the published scientific literature always emphasizing the technological aspects. The review discusses also the biomaterials used in the preparation of the nano and microsystems of ophthalmic drug delivery, fabrication techniques, therapeutic significances, and future possibilities in the field.Item A Safe GDNF and GDNF/BDNF Controlled Delivery System Improves Migration in Human Retinal Pigment Epithelial Cells and Survival in Retinal Ganglion Cells: Potential Usefulness in Degenerative Retinal Pathologies(Pharmaceuticals, 2021) Arranz Romera, Alicia; Hernandez, Maria; Checa Casalengua, Patricia; García Layana, Alfredo; Molina Martínez, Irene Teresa; Recalde, Sergio; Young, Michael J.; Tucker, Budd A.; Fernández Robredo, Patricia; Herrero Vanrell, María Del Rocío; Bravo Osuna, IreneWe assessed the sustained delivery effect of poly (lactic-co-glycolic) acid (PLGA)/vitamin E (VitE) microspheres (MSs) loaded with glial cell-derived neurotrophic factor (GDNF) alone (GDNF-MSs) or combined with brain-derived neurotrophic factor (BDNF; GDNF/BDNF-MSs) on migration of the human adult retinal pigment epithelial cell-line-19 (ARPE-19) cells, primate choroidal endothelial (RF/6A) cells, and the survival of isolated mouse retinal ganglion cells (RGCs). The morphology of the MSs, particle size, and encapsulation efficiencies of the active substances were evaluated. In vitro release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability, terminal deoxynucleotidyl transferase (TdT) deoxyuridine dUTP nick-end labelling (TUNEL) apoptosis, functional wound healing migration (ARPE-19; migration), and (RF/6A; angiogenesis) assays were conducted. The safety of MS intravitreal injection was assessed using hematoxylin and eosin, neuronal nuclei (NeuN) immunolabeling, and TUNEL assays, and RGC in vitro survival was analyzed. MSs delivered GDNF and co-delivered GDNF/BDNF in a sustained manner over 77 days. The BDNF/GDNF combination increased RPE cell migration, whereas no effect was observed on RF/6A. MSs did not alter cell viability, apoptosis was absent in vitro, and RGCs survived in vitro for seven weeks. In mice, retinal toxicity and apoptosis was absent in histologic sections. This delivery strategy could be useful as a potential co-therapy in retinal degenerations and glaucoma, in line with future personalized long-term intravitreal treatment as different amounts (doses) of microparticles can be administered according to patients’ needs.Item 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 RocíoThe 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.