Facultad de Ciencias de la Salud

The objective of this research was to develop and evaluate an ocular insert for the controlled drug delivery of moxifloxacin which could perhaps be used in the treatment of corneal keratitis or even bacterial endophthalmitis. We have evaluated the ex vivo ocular diffusion of moxifloxacin through rabbit cornea, both fresh and preserved under different conditions. Histological studies were also carried out. Subsequently, drug matrix inserts were prepared using bioadhesive polymers. The inserts were evaluated for their physicochemical parameters. Ophthalmic ex vivo permeation of moxifloxacin was carried out with the most promising insert. The formulate insert was thin and provided higher ocular diffusion than commercial formulations. Ocular diffusion studies revealed significant differences between fresh and frozen corneas. Histological examinations also showed differences in the thickness of stroma between fresh and frozen corneas. The ophthalmic insert we have developed allows a larger quantity of moxifloxacin to permeate through the cornea than existing commercial formulations of the drug. Ocular delivery of moxifloxacin with this insert could be a new approach for the treatment of eye diseases.

Progesterone (PG) has been shown to have a slowing effect on photoreceptor cell death in mouse models of retinitis pigmentosa when administered orally. The aim of this study was to investigate whether ophthalmically administered progesterone was able to reach neuroretina and thus, the distribution through ocular tissues of different PG formulations was studied. The effect of different initial PG concentration was also investigated. Different formulations with PG in their composition (drops, a corneal/scleral-insert and scleral-inserts) were prepared and assayed. Using whole porcine eyes, the different formulations were topically administered to the ocular surface. Frozen eyes were dissected, the PG in each tissue was extracted in acetonitrile and the amount of PG quantified by UHPLC-MS/MS. Our results show that after topical administration, PG diffuses from the ocular surface and distributes throughout all tissues of the eye. Lower levels of PG were found in sclera, choroid and neuroretina when PG was applied as drops compared to inserts. Our results also show that an increase in the initial PG concentrations applied, resulted in a statistically significant increase in the amounts of PG in aqueous humour, sclera, choroid and neuroretina.

Progesterone (PG) diminishes free radical damage and thus can afford protection against oxidative stress affecting the retina. The therapeutic use of PG is limited because it is a highly hydrophobic steroid hormone with very low solubility in water. This is the main drawback for the therapeutic application of PG at ocular level. The aims of this study were: (i) to analyze if PG causes ocular irritation (ii) to validate a HPLC method to determine PG in ex vivo studies and (iii) to evaluate PG permeation through cornea and sclera. A high performance liquid chromatographic method was developed and validated to detect PG incorporated to β-cyclodextrin using a Waters Sunfire C18 (150 × 4.6 mm) reverse-phase column packed with 5 μm silica particles using a mobile phase consisted of a mixture of acetonitrile (ACN) and pure water 80:20 (v/v), pH 7.4. The limit of detection and the limit of quantification for 50 μL injection of PG were found to be 0.42 and 1.26 μg/mL, respectively. The calibration curve showed excellent linearity over the concentration range (0.5 μg/mL to 100 μg/mL). As proof of concept, ex-vivo experiments to investigate PG permeation through cornea and sclera with vertical diffusion cells were carried out to quantify PG diffusion. Ex vivo experiments demonstrate its applicability to investigate permeation levels of PG from 6.57 ± 0.37 μg/cm2 at cornea and 8.13 ± 0.85 μg/cm2 sclera. In addition, at the end of diffusion studies the amount of PG retained in each tissue was also quantified, and it was 40.87 ± 9.84 μg/cm2 (mean ± SD; n = 6) in cornea and 56.11 ± 16.67 μg/cm2 (mean ± SD; n = 6) in sclera.

Progesterone (PG) affords neuroprotection in degenerative diseases associated to oxidative stress, such as cataracts, age-related macular degeneration, glaucoma, diabetic retinopathy and retinitis pigmentosa. The aim of this project was to develop ocular inserts for delivery of PG to the eye. Different inserts with PG in its composition were formulated and the insert with the best characteristics (59% polyvinyl alcohol, 39% polyvinylpyrrolidone K30 and 2% propylene glycol) was selected for ex vivo studies. Physical characteristics and drug release patterns of the insert were analysed. In vitro diffusion studies revealed a controlled diffusion of progesterone. Ex vivo experiments demonstrated similar trans-corneal and trans-scleral PG diffusion (corneal apparent permeability coefficient 6.46 ± 0.38 × 10-7 cm/s and scleral apparent permeability coefficient 5.87 ± 1.18 × 10- 7 cm/s; mean ± SD; n = 5). However, the amount of PG accumulated in scleras was statistically higher than in corneas (30.07 ± 9.09 μg/cm2 and 15.56 ± 4.36 μg/cm2 respectively). The PG-loaded inserts (55.6 μg/cm2) were thin, translucent, showed no irritancy (HET-CAM test) and were elastic and robust, all suitable properties for its potential use in the treatment of several ocular diseases.

International Nonproprietary Names (INN) are assigned by the World Health Organization (WHO) to pharmaceutical substances to ensure global recognition by a unique name. INN facilitate safe prescribing through naming consistency, efficient communication and exchange of information, transnational access and pharmacovigilance of medicinal products. Traditional vaccines such as inactivated or live-attenuated vaccines have not been assigned INN and provision of a general name falls within the scope of the WHO Expert Committee on Biological Standardization (ECBS). However, novel vaccines that contain welldefined active ingredients such as nucleic acids or recombinant proteins fulfil the criteria to be assigned INN. In the current environment where multiple SARS-CoV-2 vaccines are being developed to combat the COVID-19 pandemic and with virus variants emerging, assigning INN to well-defined vaccine substances will strengthen pharmacovigilance and ultimately enhance the safety of vaccine recipients. This article examines the background to INN for vaccines and explains the applicability and value of assigning INN to novel well-defined vaccines.

Retinitis pigmentosa (RP) is an inherited eye disorder which triggers a cascade of retinal disorders leading to photoreceptor cell death and for which there is currently no effective treatment. The purpose of this research was to study whether ocular administration of a solution of progesterone (PG) in -cyclodextrins (CD) could delay photoreceptor cell death and counteract the gliosis process in an animal model of RP (rds mice). The possible effect of PG reaching the contralateral eye through the circulatory system was also evaluated. Finally, this research discusses and evaluates the diffusion of the drug from possible topical formulations for ocular administration of PG. A group of rds mice received one drop of a solution of PG in CD every 12 h for 10 days to the left eye, while the right eye was left untreated. Another group of rds mice (control) received the drug vehicle (PBS) on the left eye and, again, the right eye was left untreated. Once the treatment was finished on postnatal day 21, the animals were euthanized and histological immunofluorescence studies (TUNEL, GFAP, and DAPI staining) were carried out. Our results showed that the administration of a solution of PG in CD (CD-PG) as drops significantly decreased cell death and inflammation in the retina of the PG-treated eyes of rds mice. No effect was seen in the contralateral eye from PG that may have entered systemic circulation. In conclusion, CD-PG applied topically as drops to the eye decreases photoreceptor cell death in the early stages of RP, delaying vision loss and decreasing gliosis.

Background: Postoperative cognitive dysfunction affects the quality of recovery, particularly affecting the elderly, and poses a burden on the health system. We hypothesize that the use of sugammadex (SG) could optimize the quality of postoperative cognitive function and overall recovery through a neuroprotective effect. Methods: A pilot observational study on patients undergoing cardiac surgery with enhanced recovery after cardiac surgery (ERACS) approach, was designed to compare SG-treated (n = 14) vs. neostigmine (NG)-treated (n = 7) patients. The Postoperative Quality Recovery Scale (PQRS) was used at different times to evaluate cognitive function and overall recovery of the patients. An online survey among anesthesiologists on SG use was also performed. Additionally, an animal model study was designed to explore the effects of SG on the hippocampus. Results: Sugammadex (SG) was associated with favorable postoperative recovery in cognitive domains particularly 30 days after surgery in patients undergoing aortic valve replacement by cardiopulmonary bypass and the ERACS approach; however, it failed to demonstrate a short-term decrease in length of intensive care unit (ICU) and hospital stay. The survey information indicated a positive appreciation of SG recovery properties. SG reverts postoperative memory deficit and induces the expression of anti-inflammatory microglial markers. Conclusion: The results show a postoperative cognitive improvement by SG treatment in patients undergoing aortic valve replacement procedure by the ERACS approach. Additionally, experimental data from an animal model of mild surgery confirm the cognitive effect of SG and suggest a potential effect over glia cells as an underlying mechanism.

In recent years, the use of 3D printing technologies in orthopedic surgery has markedly increased, as they offer the possibility of printing personalized prostheses. The work presented in this article is a preliminary study of a research project which aims to manufacture customized spacers containing antibiotics for use in joint replacement surgery. The objective of this work was to design and print different 3D constructs to evaluate the use of different materials, their properties after the process of 3D printing, such as resistance, and the release kinetics of drugs from the constructs. Different designs and different materials were analyzed to obtain a 3D construct with suitable properties. Our design takes advantage of the micropores created between the layers of the 3D printed filaments to release the contained drug. Using polylactic acid (PLA) we were able to print cylindrical structures with interconnected micropores and a hollow chamber capable of releasing methylene blue, which was selected as a model drug. The final PLA 3D construct was printed with a 10% infill. The physical and technological characteristics, morphological changes at body temperature and interaction with water were considered to be acceptable. The PLA 3D printed constructs were found to have sufficient strength to withstand a force of 500 kg. The results obtained allow to continue research in this project, with the aim of manufacturing prostheses containing a reservoir of antibiotics or other drugs in their interior for their subsequent controlled release.

Introducción: El presente artículo forma parte de un proyecto que pretende formar a estudiantes en la observación de la enfermedad utilizando para ello obras de arte. Los objetivos son desarrollar el interés científico de los participantes, promover y desarrollar la afición por el arte en estudiantes con formación básicamente científica. La peste negra, aunque fue una de las mayores catástrofes del mundo pre-modernista, produjo un obligado avance en la medicina. En este contexto histórico, a través de la representación de san Roque se vislumbra el impacto social de la pandemia gracias a la herencia artística del gótico, del renacimiento y del barroco (siglos xiv a xvii). Material y métodos: Se han analizado algunas obras pictóricas sobre san Roque y, aprovechando la visión artística e histórica de su figura, se ha recopilado información de la labor y relación de san Roque con la peste bubónica. Resultados y discusión: A través de contenidos artísticos de la figura san Roque se observa una correlación bastante fidedigna entre la clínica representada en los cuadros de san Roque y los signos descritos en la medicina interna e infecciosa actual. Los signos y síntomas comunes de la peste aparecen fielmente representados en las obras analizadas dado que algunos de los pintores que dedicaron trabajos a su figura convivieron con la enfermedad e incluso la padecieron. / Introduction: This article forms part of a project intended to teach students about observation through artwork. The objectives were to promote and develop art appreciation in science students, as well to continue developing their scientific interest. Although bubonic plague was one of the greatest catastrophes in the pre-modern world, it was also partly responsible for major advances in medicine. In this historic context, and using the figure of Saint Roch, a Catholic saint and confessor especially invoked against the plague, the social impact of the pandemic is assessed using the artistic heritage of gothic, renaissance and baroque periods (fourteen to seventeenth centuries). Material and methods: Some paintings of Saint Roch have been analysed by looking at the historical and artistic viewpoints in order to gather information about his work and the relationship of the Saint with the bubonic plague. Results and discussion: Through the artistic representations of Saint Roch, and after a bibliographic review, a good correlation can be established between the clinical signs shown in the paintings and those described by in current internal medicine and knowledge of infections. There is ample evidence showing the fidelity of the representations regarding the common signs and symptoms of Black Death, particularly as some of the painters who painted the Saint lived at the time of the epidemics and even suffered the disease themselves.