Person: Herrero Vanrell, María Del Rocío
Loading...
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
51 results
Search Results
Now showing 1 - 10 of 51
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 Chronic glaucoma induced in rats by a single injection of fibronectin-loaded PLGA microspheres: IOP-dependent and IOP-independent eurodegeneration(Internationl Journal of Molecular Sciences, 2024) Munuera, Inés; Aragón Navas, Alba; Villacampa, Pilar; González-Cela Casamayor, Miriam Ana; Subías, Manuel; Pablo, Luis E.; García Feijoo, Julián; Herrero Vanrell, María Del Rocío; García Martín, Elena Salobrar; Bravo Osuna, Irene; Rodrigo, María J.To evaluate a new animal model of chronic glaucoma induced using a single injection of fibronectin-loaded biodegradable PLGA microspheres (Ms) to test prolonged therapies. 30 rats received a single injection of fibronectin-PLGA-Ms suspension (MsF) in the right eye, 10 received non-loaded PLGA-Ms suspension (Control), and 17 were non-injected (Healthy). Follow-up was performed (24 weeks), evaluating intraocular pressure (IOP), optical coherence tomography (OCT), histology and electroretinography. The right eyes underwent a progressive increase in IOP, but only induced cohorts reached hypertensive values. The three cohorts presented a progressive decrease in ganglion cell layer (GCL) thickness, corroborating physiological age-related loss of ganglion cells. Injected cohorts (MsF > Control) presented greater final GCL thickness. Histological exams explain this paradox: the MsF cohort showed lower ganglion cell counts but higher astrogliosis and immune response. A sequential trend of functional damage was recorded using scotopic electroretinography (MsF > Control > Healthy). It seems to be a function–structure correlation: in significant astrogliosis, early functional damage can be detected by electroretinography, and structural damage can be detected by histological exams but not by OCT. Males presented higher IOP and retinal and GCL thicknesses and lower electroretinography. A minimally invasive chronic glaucoma model was induced by a single injection of biodegradable Ms.Item 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 RocíoThis 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.Item Evaluation of polyesteramide (PEA) and polyester (PLGA) microspheres as intravitreal drug delivery systems in albino rats(Biomaterials, 2017) Peters, Tobias; Kim, Seong-Woo; Castro, Vinicius; Stingl, Krunoslav; Strasser, Torsten; Bolz, Sylvia; Schraermeyer, Ulrich; Mihov, George; Zong, MengMeng; Andrés Guerrero, Vanesa; Herrero Vanrell, María Del Rocío; Dias, Aylvin; Cameron, Neil; Zrenner, EberhartPurpose: To study the suitability of injectable microspheres based on poly(ester amide) (PEA) or poly lactic-co-glycolic acid (PLGA) as potential vehicles for intravitreal drug delivery in rat eyes. Dexamethasone loaded PEA microspheres (PEA+DEX) were also evaluated. Methods: Forty male Sprague Dawley rats were divided into four groups that received different intravitreally injected microspheres: PEA group (n=12); PLGA group (n=12); PEA+DEX group (n=8); and control group (no injection, n=8). Electroretinography (ERG), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (sdOCT) were performed at baseline, weeks 1 and 2, and months 1, 2, and 3 after intravitreal injection. Eyes were histologically examined using light microscopy and transmission electron microscopy at the end of the in vivo study. Results: There were no statistically significant changes in ERG among the groups. Abnormal FAF pattern and abnormal deposits in OCT were observed after injection but almost completely disappeared between week 2 and month 3 in all injected groups. GFAP staining showed that Müller glia cell activation was most pronounced in PLGA-injected eyes. Increased cell death was not observed by TUNEL staining at month 1. In electron microscopy at month 3, the remnants of microparticles were found in the retinal cells of all injected groups, and loss of plasma membrane was seen in the PLGA group. Conclusions: Although morphological changes such as mild glial activation and material remnants were observed histologically 1 month and 3 months after injection in all injected groups, minor cell damage was noted only in the PLGA group at 3 months after injection. No evidence of functional abnormality relative to untreated eyes could be detected by ERG 3 months after injection in all groups. Changes observed in in vivo imaging such as OCT and FAF disappeared after 3 months in almost all cases.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 Performance of the rebound, noncontact and Goldmann applanation tonometers in routine clinical practice(Acta Ophthalmologica, 2011) Martínez De La Casa Fernández-Borrella, José María; Jimenez-Santos, M; Saenz Frances, F; Matilla-Rodero, M; Méndez Hernández, Carmen Dora; Herrero Vanrell, María Del Rocío; García Feijoo, JuliánPurpose: To compare rebound tonometry (RBT) and noncontact tonometry (NCT) using Goldmann applanation tonometry (GAT) as reference. Methods: The study sample was comprised of 108 eyes of 108 subjects consecutively examined at a general ophthalmology clinic. The order of use of the three tonometers was randomized at the study outset. The difference between the methods was plotted against the mean to compare the tonometers. The hypothesis of zero bias was examined by a paired t-test and 95% limits of agreement (LoA) were also calculated. Differences with respect to GAT were assessed according to the international standard for ocular tonometers (ISO 8612). Results: Mean intraocular pressures (IOPs ± SD) obtained using the three instruments were GAT 17.5 ± 3.8 mmHg; RBT 18.5 ± 5.5 mmHg and NCT 17.4 ± 5.6 mmHg. The 95% LoA were from -7.9 to +7.7 mmHg for NCT-GAT and from -6.8 mmHg to +8.7 mmHg for RBT-GAT. A difference with respect to GAT under ±1 mmHg was observed in 11.1% of the eyes measured by NCT and 18.5% of eyes measured by RBT. According to the IOP ranges established by the ISO 8612, differences from GAT measurements greater than ±5 mmHg were always above the accepted level of 5%. Correlations between IOP and central corneal thickness (CCT) were significant for all three tonometers. Conclusions: The rebound and noncontact tonometer behaved similarly when used to measure IOP taking GAT measurements as the reference standard. Neither tonometer fulfilled ISO 8612 requirements. Both were similarly influenced by CCT. © 2009 The Authors. Journal compilation © 2009 Acta Ophthalmol.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.