Person:
Herrero Vanrell, María Del Rocío

First Name

María Del Rocío

Last Name

Herrero Vanrell

URI

https://hdl.handle.net/20.500.14352/77475

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Farmacia

Department

Farmacia Galénica y Tecnología Alimentaria

Area

Farmacia y Tecnología Farmaceútica

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Now showing 1 - 10 of 24

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.
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.
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, Eberhart
Purpose: 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.
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 Rocío
Efficient 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.
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.
Current Perspectives on the Use of Anti-VEGF Drugs as Adjuvant Therapy in Glaucoma
(Advances in Therapy, 2017) Andrés Guerrero, Vanesa; Perucho González, Lucía; García Feijoo, Julián; Morales Fernández, Laura; Sáenz Francés, Federico; Herrero Vanrell, María Del Rocío; Pablo Júlvez, Luis; Polo Llorens, Vicente; Martínez De La Casa Fernández-Borrella, José María; Konstas, Anastasios Georgios P.
The approval of one of the first anti-vascular endothelial growth factor (VEGF) agents for the treatment of neovascular age-related macular degeneration one decade ago marked the beginning of a new era in the management of several sight-threatening retinal diseases. Since then, emerging evidence has demonstrated the utility of these therapies for the treatment of other ocular conditions characterized by elevated VEGF levels. In this article we review current perspectives on the use of anti-VEGF drugs as adjuvant therapy in the management of neovascular glaucoma (NVG). The use of anti-VEGFs for modifying wound healing in glaucoma filtration surgery (GFS) is also reviewed. Selected studies investigating the use of anti-VEGF agents or antimetabolites in GFS or the management of NVG have demonstrated that these agents can improve surgical outcomes. However, anti-VEGF agents have yet to demonstrate specific advantages over the more established agents commonly used today. Further studies are needed to evaluate the duration of action, dosing intervals, and toxicity profile of these treatments.
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.
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
Trojan Microparticles Potential for Ophthalmic Drug Delivery
(Current Medicinal Chemistry, 2019) Esteban Pérez, Sergio; Bravo Osuna, Irene; Andrés Guerrero, Vanesa; Molina Martínez, Irene Teresa; Herrero Vanrell, María Del Rocío
The administration of drugs to treat ocular disorders still remains a technological challenge in this XXI century. Although there is an important arsenal of active molecules useful to treat ocular diseases, ranging from classical compounds to biotechnological products, currenty, no ideal delivery system is able to profit all their therapeutic potential. Among the intraocular drug delivery systems (IODDS) proposed to overcome some of the most important limitations, microsystems and nanosystems have raised high attention. While microsystems are able to offer long-term release after intravitreal injection, nanosystems can protect the active compound from external environment (reducing their clearance) and direct it to its target tissues. In recent years, some researchers have explored the possibility of combining micro and nanosystems in “nanoparticle-in-microparticle (NiMs)” systems or “trojan systems”. This excellent idea is not exempt of technological problems, remains partially unsolved, especially in the case of IODDS. The objective of the present review is to show the state of art concerning the design, preparation and characterization of trojan microparticles for drug delivery and to remark their potential and limitations as IODDS, one of the most important challenges faced by pharmaceutical technology at the moment.
Amphiphilic Acrylic Nanoparticles Containing the Poloxamer Star Bayfit® 10WF15 as Ophthalmic Drug Carriers
(Polymers, 2019) Gómez Ballesteros, Miguel; Andrés Guerrero, Vanesa; Parra Luna, Francisco; Marinich, Jorge; Heras Polo, Beatriz De Las; Molina Martínez, Irene Teresa; Vázquez Lasa, Blanca; San Román Del Barrio, Julio; Herrero Vanrell, María Del Rocío
Topical application of drops containing ocular drugs is the preferred non-invasive route to treat diseases that a_ect the anterior segment of the eye. However, the formulation of eye drops is a major challenge for pharmacists since the access of drugs to ocular tissues is restricted by several barriers. Acetazolamide (ACZ) is a carbonic anhydrase inhibitor used orally for the treatment of ocular hypertension in glaucoma. However, large ACZ doses are needed which results in systemic side e_ects. Recently, we synthesized copolymers based on 2-hydroxyethyl methacrylate (HEMA) and a functionalized three-arm poloxamer star (Bayfit-MA). The new material (HEMA/Bayfit-MA) was engineered to be transformed into nanoparticles without the use of surfactants, which represents a significant step forward in developing new ophthalmic drug delivery platforms. Acetazolamide-loaded nanocarriers (ACZ-NPs) were prepared via dialysis (224 +/- 19 nm, ̶ 17.2 +/- 0.4 mV). The in vitro release rate of ACZ was constant over 24 h (cumulative delivery of ACZ: 83.3 +/- 8.4%). Following standard specifications, ACZ-NPs were not cytotoxic in vitro in cornea, conjunctiva, and macrophages. In normotensive rabbits, ACZ-NPs generated a significant intraocular pressure reduction compared to a conventional solution of ACZ (16.4% versus 9.6%) with the same dose of the hypotensive drug (20 μg). In comparison to previously reported studies, this formulation reduced intraocular pressure with a lower dose of ACZ. In summary, HEMA:Bayfit-MA nanoparticles may be a promising system for ocular topical treatments, showing an enhanced ocular bioavailability of ACZ after a single instillation on the ocular surface.