Natural deep eutectic systems – a new delivery system for ocular drugs

• Autor(a) principal: Sarmento, Célia Cristina Oliveira
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/146237
• topic: ocular diseases; oxidative stress; NADES; natural antioxidants; eye drops; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

The major goal of this work was to study the potential of natural deep eutectic systems (NADES) as new media for ocular formulations mainly due to their high viscosity, as it is an important aspect related to drugs retention time in ocular formulations. Therefore, different systems composed of combinations of sugars, polyols, amino acids, and choline derivatives were prepared. NADES were characterized through a series of various techniques to evaluate if they could be used as ocular delivery systems via topical instillation, namely rheological and physicochemical studies were carried out. In terms of viscosity, it was observed that aqueous solutions of NADES showed viscosity values within the standard values to be used as an ocular drug delivery system, i.e., within the range of 0.8 to 1.2 mPa.s. The pH of the solutions was measured, showing that the values are near the physiological value (pH 7.4). Other parameters were analyzed and when compared with commercial samples our aqueous solutions of NADES have contact angles between 100.7 and 109.9 ⁰ when measured in a hydrophobic surface, refractive indexes of 1.3404 to 1.3491, osmolality values ranged from 412 to 1883 mOsmolkg-1, and surface tension between 60.28 and 71.57 mN/m. All values were within the values obtained for commercial samples. The cytotoxicity assays demonstrated that, in general, these systems are biocompatible, promoting cell viability, i.e., above 80% metabolic activity when compared to control, after 24h incubation in ARPE-19 cells, and therefore do not cause harm in ocular cells. Furthermore, rutin, resveratrol and taurine, three relevant antioxidants for ocular applications, were successfully dissolved in NADES, and their stability was determined at predetermined timepoints. The results showed that the antioxidant activity is not significantly altered up to 6 months and using NADES as excipients might be useful to extend the shelf-life of ocular drops. Overall, the results suggest that NADES are potential excipients to be used in ocular formulations.