Can (Natural) deep eutectic systems increase the efficacy of ocular therapeutics?

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.

Using Natural Deep Eutectic Systems as Alternative Media for Ocular Applications.

The major goal of this work was to study the potential of natural deep eutectic systems (NADES) as new media for ocular formulations. In formulating eye drops, it is important to increase the retention time of the drug on the surface of eye; hence, due to their high viscosity, NADES may be interesting candidates for formulation. Different systems composed of combinations of sugars, polyols, amino acids, and choline derivatives were prepared and then characterized in terms of rheological and physicochemical properties. Our results showed that 5-10% (w/v) aqueous solutions of NADES have a good profile in terms of viscosity (0.8 to 1.2 mPa.s), osmolarity (412 to 1883 mOsmol), and pH (7.4) for their incorporation of ocular drops. Additionally, contact angle and refractive index were determined. Acetazolamide (ACZ), a highly insoluble drug used to treat glaucoma, was used as proof-of-concept. Herein, we show that NADES can increase the solubility of ACZ in aqueous solutions by at least up to 3 times, making it useful for the formulation of ACZ into ocular drops and thereby enabling more efficient treatment. The cytotoxicity assays demonstrated that NADES are biocompatible up to 5% (w/v) in aqueous media, promoting cell viability (above 80%) when compared to the control after 24 h incubation in ARPE-19 cells. Furthermore, when ACZ is dissolved in aqueous solutions of NADES, the cytotoxicity is not affected in this range of concentrations. Although further studies are necessary to design an optimal formulation incorporating NADES, this study shows that these eutectics can be powerful tools in the formulation of ocular drugs.

Caracterização e avaliação da pastagem do rebanho de agricultores familiares do nordeste paraense / Characterization an evaluation of pastures and cattle at smallholder agriculturalists in northeast Pará State, Brazil

No Nordeste Paraense alguns agricultores familiares têm implantado pequenas áreas de pastagens e manejado pequenos rebanhos com o objetivo de aplicar eventuais ganhos obtidos com os cultivos, criando uma poupança a ser utilizada nas necessidades futuras da família ou da propriedade. Há indícios de problemas nas pastagens e no rebanho que limitam tanto a produção e a sustentabilidade da pecuária, como comprometem os cultivos agrícolas que realmente sustentam a propriedade. Este estudo tratou de identificar as principais limitações e propor alternativas de manejo que sejam econômica e ecologicamente mais sustentáveis. Na primeira fase do estudo, numa amostra ao acaso de 38 propriedades, descreveu-se o manejo da pastagem e do rebanho, e na segunda, numa amostra menor, de doze propriedades e por um período de 29 meses, avaliou-se o potencial desses dois componentes. As propriedades estudadas desenvolvem uma pecuária de baixa produtividade. Devido à baixa fertilidade do solo e o deficiente manejo, as pastagens não suprem os alimentos necessários ao rebanho, tanto em quantidade como em qualidade. Também foram identificadas deficiências no manejo do rebanho, próprias de sistemas extensivos. Contudo, as limitações podem ser solucionadas com práticas amplamente conhecidas de manejo da pastagem (como formação, manutenção e manejo) e do rebanho (reprodução, manejo de bezerros e sanidade em geral). Novos modelos de exploração também foram sugeridos.

In Northeastern Pará, smallholder agriculturalists have established small pastures and manage small herds, mainly with the objective of investing profits in their crops, as a form of savings to meet the family's and property's future needs. There are indications of pasture and herd problems that limit production and sustainability, and threaten the crops that really sustain the property. This study sought to identify constraints and technological solutions, and make information available for public policies. In the 1st phase of this study and using 38 smallholdings sampled at random, the pastures and herd management were described, and in the 2nd phase, with a smaller sample of 12 smallholdings during 29-month period, the potential of these two components was evaluated. In general, the smallholdings have low-productivity and ranching is vulnerable. Due to the low soil fertility and the deficient management, pastures do not supply all the herd's feed needs, neither in quantity nor quality. Herd management deficiencies are characteristic of extensive production systems. However, these constraints can be overcome with well-known technologies of pasture establishment, maintenance and management, and herd reproduction, calf management, and herd health, allowing significant improvement. New exploitation models were suggested also.