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2024
Sarmento, Célia, Ana Rita C. Duarte, and Ana Rita Jesus. "Can (Natural) deep eutectic systems increase the efficacy of ocular therapeutics?" European Journal of Pharmaceutics and Biopharmaceutics. 198 (2024): 114276. AbstractWebsite

The eye is one of the most complex organs in the human body, with a unique anatomy and physiology, being divided into anterior and posterior segments. Ocular diseases can occur in both segments, but different diseases affect different segments. Glaucoma and cataracts affect the anterior segment, while macular degeneration and diabetic retinopathy occur in the posterior segment. The easiest approach to treat ocular diseases, especially in the anterior segment, is through the administration of topical eye drops, but this route presents many constraints, namely precorneal dynamic and static ocular barriers. On the other hand, the delivery of drugs to the posterior segment of the eye is far more challenging and is mainly performed by the intravitreal route. However, it can lead to severe complications such as retinal detachment, endophthalmitis, increased intraocular pressure and haemorrhage. The design of new drug delivery systems for the anterior segment is very challenging, but targeting the posterior one is even more difficult and little progress has been made. In this review we will discuss various strategies including the incorporation of additives in the formulations, such as viscosity, permeability, and solubility enhancers, namely based on Deep eutectic systems (DES). Natural deep eutectic systems (NADES) have emerged to solve several problems encountered in pharmaceutical industry, regarding the pharmacokinetic and pharmacodynamic properties of drugs. NADES can contribute to the design of advanced technologies for ocular therapeutics, including hydrogels and nanomaterials. Here in, we revise some applications of (NA)DES in the development of new drug delivery systems that can be translated into the ophthalmology field.

Viñas-Ospino, Adriana, Ana Rita Jesus, Alexandre Paiva, Maria J. Esteve, Ana Frígola, Jesús Blesa, and Daniel López-Malo. "Comparison of green solvents for the revalorization of orange by-products: Carotenoid extraction and in vitro antioxidant activity." Food Chemistry. 442 (2024): 138530. AbstractWebsite

Orange peels contain a considerable number of bioactive compounds such as carotenoids, that can be used as ingredients in high-value products. The aim of this study was to compare orange peel extracts obtained with different green solvents (vegetable oils, fatty acids, and deep eutectic solvents (DES)). In addition, the chemical characterization of a new hydrophobic DES formed by octanoic acid and l-proline (C8:Pro) was performed. The extracts were compared in terms of carotenoid extraction, antioxidant activity by three methods, color, and environmental impact. The results confirmed that the mixture of C8:Pro is a DES and showed the highest carotenoid extraction (46.01 µg/g) compared to hexane (39.28 µg/g). The antioxidant activity was also the highest in C8:Pro (2438.8 µM TE/mL). Finally, two assessment models were used to evaluate the greenness and sustainability of the proposed extractions. These results demonstrated the potential use of orange peels in the circular economy and industry.

2023
Jesus, Ana Rita, Alexandre Paiva, and Ana Rita C. Duarte. "Current developments and future perspectives on biotechnology applications of natural deep eutectic systems." 39 (2023): 100731. AbstractWebsite

Natural Deep Eutectic Systems (NADES) have emerged in the past years as alternative solvents to traditional organic solvents and ionic liquids. NADES are easy to produce, sustainable, biocompatible, eco-friendly, remarkable solubilizing agents, and highly task-specific. The outstanding properties of this new liquid media have attracted the attention of researchers in the last decade in many fields and biotechnology is probably one of the fields where NADES have gained more relevance. Nonetheless, the progress beyond the state of the art in this field is not yet fully explored. Most research papers regarding the use of NADES in biotechnology are related to their use as solubility enhancers for poorly soluble active ingredients, particularly for pharmaceutical applications. However, the applicability of NADES in applications such as cryopreservation, stabilization of proteins and DNA, as well as other biomedical applications, has only recently been explored and presents still a plethora of discoveries to be unravelled. The current developments in this scientific field and future perspectives will be discussed herein.

2022
Ferreira, Inês João, Filipe Oliveira, Ana Rita Jesus, Alexandre Paiva, and Ana Rita C. Duarte. "Current methodologies for the assessment of deep eutectic systems toxicology: Challenges and perspectives." 362 (2022): 119675. AbstractWebsite

Deep eutectic systems (DES) are a mixture of two or more components where at least one works as a hydrogen bond acceptor (HBA) and another as a hydrogen bond donor (HBD). DES most distinctive characteristic is the fact that the mixture possesses a lower melting point, when compared to the melting point of its individual components. These systems have emerged as a “greener alternative” to organic solvents, while also offering several advantages over other “green” solvents such as ionic liquids (IL). However, the number of studies concerning the real biodegradability and biocompatibility are scarce and the methodologies are scattered through different articles. Current state of the art provides several reports using different models, namely using prokaryotic and eukaryotic cells but also more complex models considering whole organisms, such as plants and animals, attempting to understand DES toxicity at different complexity levels. The currently used methodologies is very different among authors, thus the standardization is urgently needed. This review’s purpose is to summarize the available data about DES toxicity, biocompatibility and biodegradability, while also assembling the different methodologies used in an effort to pave the way so that standard guidelines for future research work are established.