ABSTRACT
Contact lenses (CLs) have been suggested as drug delivery platforms capable of increasing the drug residence time on the cornea and therefore its bioavailability. However, when targeting the posterior segment of the eye, the drug released from CLs still encounters the barrier effect of the ocular tissues, which considerably reduces the efficacy of administration. This work aims at the development of CLs able to simultaneously deliver an anti-inflammatory drug (dexamethasone sodium phosphate) and a cell-penetrating peptide (penetratin), the latter acting as a drug carrier across the tissues. Hydroxyethyl methacrylate (HEMA)-based hydrogels were functionalized with acrylic acid (AAc) and/or aminopropyl methacrylamide (APMA) to serve as CL materials with increased affinity for the drug and peptide. APMA-functionalized hydrogels sustained the dual release for 8 h, which is compatible with the wearing time of daily CLs. Hydrogels demonstrated suitable light transmittance, swelling capacity and in vitro biocompatibility. The anti-inflammatory activity of the drug was not compromised by the presence of the peptide nor by sterilization. The ocular distribution of the drug after 6 h of CL wearing was evaluated in vivo in rabbits and revealed that the amount of drug in the cornea and aqueous humor significantly increased when the drug was co-delivered with penetratin.
Subject(s)
Cell-Penetrating Peptides , Contact Lenses , Animals , Rabbits , Drug Delivery Systems , Drug Carriers , Dexamethasone , Anti-Inflammatory Agents , Permeability , HydrogelsABSTRACT
El conocimiento nutricional es clave para la formación de hábitos alimentarios y en la modulación del comportamiento alimentario. La alimentación y nutrición son cruciales durante la adolescencia sobre todo en jóvenes deportistas. El objetivo de esta investigación fue analizar la validez teórica y los índices de discriminación y dificultad del cuestionario de conocimientos nutricionales aplicados en el deporte utilizando la teoría de respuesta al ítem en deportistas juveniles de 14 a 19 años. Este estudio instrumental se desarrolló en cinco fases: generación de ítems, revisión por panel de expertos, pilotaje, aplicación y depuración final. Participaron 261 adolescentes de 14 a 19 años e integrantes de disciplinas colectivas en selecciones Nacional y clubes profesionales. Se determinaron los índices de dificultad y de discriminación para cada uno de los ítems. Los ítems 1 (0,354) y 2 (0,285) del factor antes, 3 (0,315) y 6 (0,408) del factor durante, 7 (0,354) y 10 (0,408) del factor después, 3 (0,254) y 9 (0,231) del factor hidratación y, 2 (0,362) y 5 (0,323) del factor suplementación, fueron los que presentaron mayor grado de discriminación. El cuestionario de conocimientos nutricionales aplicados en el deporte está compuesto por 30 ítems divididos en cinco factores cada uno de ellos con seis ítems. La propuesta inicial del cuestionario es una herramienta valida teóricamente y con índices de dificultad y discriminación adecuados para evaluar el conocimiento nutricional en jóvenes deportistas. Su aplicación permite conocer potenciales brechas en conocimientos claves y diseñar estrategias educativas específicas para subsanarlas.
Nutritional knowledge plays a fundamental role in the formation of dietary habits and the modulation of eating behaviour. Nutrition and diet are crucial during adolescence, especially for young athletes. The purpose of this research was to analyse the theoretical validity and indices of discrimination and difficulty of the questionnaire on nutritional knowledge applied in sports using item response theory in youth athletes aged 14 to 19. This instrumental study was conducted in five phases: item generation, expert panel review, pilot testing, application, and final refinement. A total of 261 adolescents aged 14 to 19, who were members of national team and collective disciplines of professional clubs, participated. Difficulty and discrimination indices were determined for each item. Items 1 (0.354) and 2 (0.285) of the before factor, 3 (0.315) and 6 (0.408) of the during factor, 7 (0.354) and 10 (0.408) of the post factor, 3 (0.254) and 9 (0.231) of the hydration factor, and 2 (0.362) and 5 (0.323) of the supplementation factor showed the highest degree of discrimination. The questionnaire on nutritional knowledge applied in sports consists of 30 items divided into five factors, each with six items. The initial questionnaire proposal is a theoretically valid tool and with adequate difficulty and discrimination indices to evaluate nutritional knowledge in young athletes. Its application allows for identifying potential gaps in key knowledge and designing specific educational strategies to address them.
ABSTRACT
Corticosteroids, although highly effective for the treatment of both anterior and posterior ocular segment inflammation, still nowadays struggle for effective drug delivery due to their poor solubilization capabilities in water. This research work aims to develop nanostructured lipid carriers (NLC) intended for periocular administration of dexamethasone acetate to the posterior segment of the eye. Pre-formulation studies were initially performed to find solid and liquid lipid mixtures for dexamethasone acetate solubilization. Pseudoternary diagrams at 65 °C were constructed to select the best surfactant based on the macroscopic transparency and microscopic isotropy of the systems. The resulting NLC, obtained following an organic solvent-free methodology, was composed of triacetin, Imwitor® 491 (glycerol monostearate >90%) and tyloxapol with Z-average = 106.9 ± 1.2 nm, PDI = 0.104 ± 0.019 and zeta potential = -6.51 ± 0.575 mV. Ex vivo porcine sclera and choroid permeation studies revealed a considerable metabolism in the sclera of dexamethasone acetate into free dexamethasone, which demonstrated higher permeation capabilities across both tissues. In addition, the NLC behavior once applied onto the sclera was further studied by means of multiphoton microscopy by loading the NLC with the fluorescent probe Nile red.
ABSTRACT
Nanotherapeutics based on biocompatible lipid matrices allow for enhanced solubility of poorly soluble compounds in the treatment of ophthalmic diseases, overcoming the anatomical and physiological barriers present in the eye, which, despite the ease of access, remains strongly protected. Micro-/nanoemulsions, solid lipid nanoparticles (SLN) or nanostructured lipid carriers (NLC) combine liquid and/or solid lipids with surfactants, improving drug stability and ocular bioavailability. Current research and development approaches based on try-and-error methodologies are unable to easily fine-tune nanoparticle populations in order to overcome the numerous constraints of ocular administration routes, which is believed to hamper easy approval from regulatory agencies for these systems. The predictable quality and specifications of the product can be achieved through quality-by-design (QbD) implementation in both research and industrial environments, in contrast to the current quality-by-testing (QbT) framework. Mathematical modelling of the expected final nanoparticle characteristics by variation of operator-controllable variables of the process can be achieved through adequate statistical design-of-experiments (DoE) application. This multivariate approach allows for optimisation of drug delivery platforms, reducing research costs and time, while maximising the understanding of the production process. This review aims to highlight the latest efforts in implementing the design of experiments to produce optimised lipid-based nanocarriers intended for ophthalmic administration. A useful background and an overview of the different possible approaches are presented, serving as a starting point to introduce the design of experiments in current nanoparticle research.
