Miguel González-Barcia
University of Santiago de Compostela
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Publication
Featured researches published by Miguel González-Barcia.
International Journal of Pharmaceutics | 2015
Anxo Fernández-Ferreiro; Maria Santiago-Varela; María Gil-Martínez; Tomas García-Caballero Parada; Maria Pardo; Miguel González-Barcia; Antonio Piñeiro-Ces; María Teresa Rodríguez-Ares; J. Blanco-Méndez; María Jesús Lamas; F.J. Otero-Espinar
Non-steroidal anti-inflammatory drug (NSAID) eye drops are widely used to treat ocular inflammatory conditions related to ophthalmic surgical procedures, such as pseudophakic cystoid macular edema, and they have been used for off-label treatments. The most commonly used NSAIDs are diclofenac and ketorolac and the new molecules bromfenac and nepafenac have also been used. We used primary human keratocytes in cell culture in combination with a novel technology that evaluates dynamic real-time cytotoxicity through impedance analysis. This study also included classic cell viability tests (WST-1(®) and AlamarBlue(®)), wound healing assay, Hens Egg Test and an ex vivo histopathological assay. NSAIDs were shown to have important cytotoxicities and to retard the healing response. Furthermore, the new eye drops containing bromfenac and nepafenac were more cytotoxic than the more classical eye drops. Nevertheless, no immuno-histochemical changes or acute irritation processes were observed after the administration of any eye drops tested. Due to cytotoxicity and the total absence of discomfort and observable injuries after the administration of these drugs, significant corneal alterations, such as corneal melts, can develop without any previous warning signs of toxicity.
Investigative Ophthalmology & Visual Science | 2017
Anxo Fernández-Ferreiro; Jesús Silva-Rodríguez; F.J. Otero-Espinar; Miguel González-Barcia; María Jesús Lamas; A. Ruibal; Andrea Luaces-Rodríguez; Alba Vieites-Prado; Tomás Sobrino; Michel Herranz; Lara García-Varela; J. Blanco-Méndez; María Gil-Martínez; Maria Pardo; Alexis Moscoso; Santiago Medín-Aguerre; Juan Pardo-Montero; Pablo Aguiar
Purpose This work is aimed at describing the utility of positron emission tomography/computed tomography (PET/CT) as a noninvasive tool for pharmacokinetic studies of biopermanence of topical ocular formulations. Methods The corneal biopermanence of a topical ophthalmic formulation containing gellan gum and kappa carragenan (0.82% wt/vol) labeled with 18Fluorine (18F) radiotracers (18F-FDG and 18F-NaF) was evaluated by using a dedicated small-animal PET/CT, and compared with the biopermanence of an aqueous solution labeled with the same compounds. Regions of interest (ROIs) were manually drawn on the reconstructed PET images for quantifying the radioactivity concentration in the eye. The biopermanence of the formulations was determined by measuring the radioactivity concentration at different times after topical application. Additionally, cellular and ex vivo safety assays were performed to assess the safety of the performed procedures. Results Differences were observed in the ocular pharmacokinetics of the two formulations. After 1.5 hours of contact, 90% of the hydrogel remained in the ocular surface, while only 69% of the control solution remained. Furthermore, it was observed that flickering had a very important role in the approach of the trial. The application of 18F-FDG in the eye was neither irritating nor cytotoxic for human corneal epithelial cells. Conclusions The use of small-animal PET and 18F radiotracers in ocular pharmacokinetics of ophthalmic formulations is feasible and could be a safe method for future ocular pharmacokinetic studies in humans.
European Journal of Pharmaceutics and Biopharmaceutics | 2017
Anxo Fernández-Ferreiro; Jesús Silva-Rodríguez; F.J. Otero-Espinar; Miguel González-Barcia; María Jesús Lamas; A. Ruibal; Andrea Luaces-Rodríguez; Alba Vieites-Prado; Isabel Lema; Michel Herranz; Noemí Gómez-Lado; J. Blanco-Méndez; María Gil-Martínez; Maria Pardo; Alexis Moscoso; Julia Cortés; María Sánchez-Martínez; Juan Pardo-Montero; Pablo Aguiar
&NA; In last years, sensitive hydrogels have become a breakthrough in ophthalmic pharmaceutical technology aimed at developing new strategies to increase the residence time of active substances. In a previous paper, we qualitatively demonstrated the capacity of a new ion sensitive hydrogel to increase the residence time. Nevertheless, the clearance of the gel from the ocular surface was not quantifiable with the used methodology. The aim of the present work was to use a well‐established approach based on scintigraphy to quantitatively estimate the residence time of the previously proposed hydrogel. The rat corneal residence time of a topic ophthalmic formulation containing gellan gum and kappa carragenan (0.82% w/v) labeled with 99mTc‐DTPA radiotracer was evaluated and compared with the residence of an aqueous solution. Ophthalmic safety studies such as eye irritation or passage through the cornea were also carried out. After 1.5 h of contact, 77% of the hydrogel remained in the ocular surface, presenting kinetics of disappearance one‐phase decay and a half time of 262 min. We conclude that the novel ophthalmic hydrogel developed with kappa carrageenan and gellan gum remains for long periods of time on the corneal surface, presenting a drop that fits an exponential decay. Graphical abstract Figure. No caption available.
International Journal of Pharmaceutics | 2017
Andrea Luaces-Rodríguez; Victoria Díaz-Tomé; Miguel González-Barcia; Jesús Silva-Rodríguez; Michel Herranz; María Gil-Martínez; María Teresa Rodríguez-Ares; Carla García-Mazás; J. Blanco-Méndez; María Jesús Lamas; F.J. Otero-Espinar; Anxo Fernández-Ferreiro
Cystinosis is a rare autosomal recessive disorder in which cystine crystals accumulate within the lysosomes of various organs, including the cornea. Ocular treatment is based on the administration of cysteamine eye drops, requiring its instillation several times per day. We have introduced the cysteamine in two types of previously developed ocular hydrogels (ion sensitive hydrogel with the polymers gellan gum and kappa-carrageenan and another one composed of hyaluronic acid), aiming at increasing the ocular retention in order to extend the dosing interval. The biopermanence studies (direct measurements and PET/CT) show that these formulations present a high retention time on the ocular surface of rats. From the in vitro release study we determined that both hydrogels can control the release of cysteamine over time, showing a zero order kinetics during four hours. At the same time, these hydrogels could act as corneal absorption promoters, as they allow a higher permeation of cysteamine through bovine cornea compared to a solution. HET-CAM test and cytotoxicity assays show no irritation on the ocular surface. These results demonstrate that the developed formulations present a high potential as vehicles for the topical ocular administration of cysteamine.
Journal of Pharmaceutical Sciences | 2018
Victoria Díaz-Tomé; Andrea Luaces-Rodríguez; Jesús Silva-Rodríguez; Sara Blanco-Dorado; Laura García-Quintanilla; José Llovo-Taboada; J. Blanco-Méndez; Xurxo García-Otero; Rubén Varela-Fernández; Michel Herranz; María Gil-Martínez; María Jesús Lamas; Miguel González-Barcia; F.J. Otero-Espinar; Anxo Fernández-Ferreiro
Econazole is a feasible alternative treatment in the management of fungal keratitis. Nevertheless, its low water solubility is considered the main limitation to the incorporation into ophthalmic formulations. In this work, econazole nitrate is solubilized by using cyclodextrins to achieve an optimum therapeutic concentration. Phase solubility diagrams suggest α-cyclodextrin as the most effective cyclodextrin and later the inclusion complex formed with this one was characterized in solution by 1D, 2D-NMR, and molecular modeling. Econazole-α-cyclodextrin inclusion complex was included in 2 types of ocular hydrogels: a natural polysaccharides ion-sensitive hydrogel and a hyaluronic acid hydrogel. Both of them show no ocular irritation in the hens egg test on chorioallantoic membrane assay and a controlled econazole release over time. Permeability studies suggest that hydrogels do not modify the econazole nitrate permeability through bovine cornea in comparison with an econazole-α-cyclodextrin inclusion complex solution. Finally, ocular biopermanence studies performed using positron emission tomography show these hydrogels present a high retention time on the eye. Results suggest the developed formulations have a high potential as vehicles for the econazole topical ocular administration as fungal keratitis treatment.
Investigative Ophthalmology & Visual Science | 2017
Anxo Fernández-Ferreiro; Andrea Luaces-Rodríguez; Pablo Aguiar; Juan Pardo-Montero; Miguel González-Barcia; Lara García-Varela; Michel Herranz; Jesús Silva-Rodríguez; María Gil-Martínez; María Bermúdez; Alba Vieites-Prado; J. Blanco-Méndez; María Jesús Lamas; Francisco Gómez-Ulla; A. Ruibal; F.J. Otero-Espinar; Francisco Gonzalez
Purpose This work aimed at describing the time course of vitreous clearance through the use of positron emission tomography (PET) as a noninvasive tool for pharmacokinetic studies of intravitreal injection. Methods The pharmacokinetic profile of intravitreal injections of molecules labeled with 18Fluorine (18F) was evaluated in adult Sprague Dawley rats by using a dedicated small-animal PET/computed tomography scanner. Different conditions were studied: three molecules radiolabeled with 18F (18F-FDG, 18F-NaF, and 18F-Choline), three volumes of intravitreal injections (7, 4, and 2 μL), and absence or presence of eye inflammation (uveitis). Results Our results showed that there are significant pharmacokinetic differences among the radiolabeled molecules studied but not among the injected volumes. The presence or absence of uveitis was an important factor in vitreous clearance, since the elimination of the drug was clearly increased when this condition is present. Conclusions Intravitreal pharmacokinetic studies based on the use of dedicated PET imaging can be of potential interest as noninvasive tools in ophthalmic drug development in small animals.
Fungal Genomics & Biology | 2016
Anxo Fernández-Ferreiro; Miguel González-Barcia; Gil Martínez M; Blanco Méndez J; F.J. Otero-Espinar; Victoria Díaz Tome; María Jesús Lamas
Background: Fungal keratitis is a disease that has a low prevalence and poor outcome because of its minimal therapeutic spectrum. Objective: The purpose of the current study is to provide an overview of the use of antifungal topical eye drops in a third level hospital and to highlight possible improvements that can optimize their therapeutic use. Methods: Fungal keratitis cases treated in the Ophthalmology Department of a Tertiary hospital were reviewed in a four-year retrospective study. Results: For four years, 24 patients received an antifungal eye drop treatment for fungal keratitis: 20% were treated with topical fluconazole and 80% were treated with topical voriconazole (79% in monotherapy and 21% in conjunction with topical natamycin). In most cases, fungal growth was been detected and susceptibility was rarely reported, facilitating the realization of directed treatment towards the most frequently isolated fungi (Fusarium, Candida, Paecilomyces). Conclusion: In a disease with low prevalence and complicated management, we have detected improvement in the three involved departments: ophthalmology, pharmacy and microbiology.
Farmacia Hospitalaria | 2016
Anxo Fernández-Ferreiro; Miguel González-Barcia; María Gil-Martínez; María Santiago Varela; Maria Pardo; J. Blanco-Méndez; Antonio Piñeiro-Ces; María Jesús Lamas Díaz; F.J. Otero-Espinar
The use of parenteral antibiotic eye drop formulations with non-marketed compositions or concentrations, commonly called fortified antibiotic eye drops, is a common practice in Ophthalmology in the hospital setting. The aim of this study was to evaluate the in vitro ocular toxicity of the main fortified antibiotic eye drops prepared in the Hospital Pharmacy Departments. We have conducted an in vitro experimental study in order to test the toxicity of gentamicin, amikacin, cefazolin, ceftazidime, vancomycin, colistimethate sodium and imipenem-cilastatin eye drops; their cytotoxicity and acute tissue irritation have been evaluated. Cell-based assays were performed on human stromal keratocytes, using a cell-based impedance biosensor system [xCELLigence Real-Time System Cell Analyzer (RTCA)], and the Hens Egg Test for the ocular irritation tests. All the eye drops, except for vancomycin and imipenem, have shown a cytotoxic effect dependent on concentration and time; higher concentrations and longer exposure times will cause a steeper decline in the population of stromal keratocytes. Vancomycin showed a major initial cytotoxic effect, which was reverted over time; and imipenem appeared as a non-toxic compound for stromal cells. The eye drops with the highest irritating effect on the ocular surface were gentamicin and vancomycin. Those antibiotic eye drops prepared at the Hospital Pharmacy Departments included in this study were considered as compounds potentially cytotoxic for the ocular surface; this toxicity was dependent on the concentration used.
European Journal of Hospital Pharmacy-Science and Practice | 2015
Anxo Fernández-Ferreiro; Maria Santiago-Varela; María Gil-Martínez; M Pardo-Perez; Miguel González-Barcia; Antonio Piñeiro-Ces; J. Blanco-Méndez; Mj Lamas Díaz; F.J. Otero-Espinar
Background It is essential to determine the safety of ophthalmic drugs. Purpose To demonstrate any in vitro cytotoxicity of antifungal eye drops manufactured by the Hospital Pharmacy Department. Material and methods Three antifungal eye drops (voriconazole 28.67 mM, fluconazole 6.53 mM and amphotericin 1.62 mM) were tested in Human Corneal Keratocytes (HCK). Toxicity to these cells was assessed using the novel label-free and real-time monitoring xCELLigence system. Under this platform, the Cell index (CI) was used to represent cell status based on the measurement of electrical impedance. Briefly, 3,000 cells/well (E-plates 16 wells) were seeded and incubated for 24 h until the CI reached the range of 1.0–1.2 indicating about 60% cell confluence. At this stage, cell culture medium was aspirated to perform cell treatment using different concentrations of antifungal eye drops. CI values were recorded throughout the test, obtaining real-time graphs of the cells’ behaviour in contact with the antifungal and IC50 was determined (corresponding to the concentrations of compounds that inhibit cell growth by 50% compared to controls). Results The kinetic curves clearly showed that cellular response depends upon concentration and time in all antifungals tested. (These graphics will be displayed on the poster). The IC50 values obtained were 5.85 mM, 0.16 mM and 0.5 mM for voriconazole, amphotericin and fluconazole respectively. Conclusion These results may be helpful in warning of cytotoxic effects of antifungal eye drops manufactured by Hospital Pharmacy Departments which are being used in concentrations that exceed the IC50 determined. References and/or acknowledgements This work was supported by Fundación Española de Farmacia Hospitalaria and Fundación Mutua Madrileña No conflict of interest.
Pharmaceutics | 2018
Andrea Luaces-Rodríguez; Miguel González-Barcia; Maria Jose Blanco-Teijeiro; María Gil-Martínez; Francisco Gonzalez; Francisco Gomez-Ulla; María-Jesús Lamas; Francisco-Javier Otero-Espinar; Anxo Fernández-Ferreiro
Although intravitreal administration of anti-infectives represents the standard treatment for infectious endophthalmitis, the knowledge about their pharmacokinetics is still limited. In this review, we aimed to summarise the factors influencing the pharmacokinetics of the anti-infective agents. We have conducted a comprehensive review of the preclinical pharmacokinetic parameters obtained in different studies of intravitreal injections of anti-infectives performed on animals, mainly rabbits. The two aspects with the biggest influence on pharmacokinetics are the distribution in the vitreous humour and the elimination through the posterior segment. The distribution can be affected by the molecular weight of the drug, the convection flow of the vitreous, the condition of the vitreous humour depending on the age of the patient, the possible interactions between the drug and the components of the vitreous, and the presence of vitrectomy. Meanwhile, the elimination includes the metabolism of the drug, the clearance via the anterior and posterior routes, and the possible inflammation of the eye resulting from the disease. Understanding the pharmacokinetics of the anti-infectives used in clinical practice is essential for a correct application. The information provided in this review could offer guidance for selecting the best therapeutic option according to the characteristics of the drugs.