Ana Rita C. Duarte

© 2017 American Chemical Society. Recent findings have reported the reason why some living beings are able to withstand the huge thermal amplitudes between winter and summer in their natural habitats. They are able to produce metabolites decreasing deeply the crystallization temperature of water, avoiding cell disrupture due to the presence of ice crystals and overcoming osmotic effects. In vitro, the possibility to cool living cells and tissues to cryogenic temperatures in the absence of ice can be achieved through a vitrification process. Vitrification has been suggested as an alternative approach to cryopreservation and could hereafter follow an interesting biomimetic perspective. The metabolites produced by these animals are mostly sugars, organic acids, choline derivatives, or urea. When combined at a particular composition, these compounds form a new liquid phase which has been defined as Natural Deep Eutectic Solvents (NADES). In this review, we relate the findings of different areas of knowledge from evolutive biology, cryobiology, and thermodynamics and give a perspective to the potential of NADES in the development of new cryoprotective agents.

© 2017 Springer-Verlag GmbH Germany, part of Springer Nature Purpose: To perform an in vivo assessment of a newly developed biodegradable ureteral stent (BUS) produced with natural-based polymers. Methods: The BUS is based on a patented technology combining the injection process with the use of supercritical fluid technology. Study was conducted at ICVS—University of Minho (Braga, Portugal) and a total of ten domestic pigs were used. In seven animals, the experimental BUS stent was inserted, whereas in the remaining a commercially available stent was used (6-Fr Biosoft ® duo stents, Porges Coloplast, Denmark). Post-stenting intravenous pyelogram was used to evaluate the degree of hydronephrosis. The in vivo stent degradation was measured as function of the weight loss. Moreover, the tensile properties of the BUS were tested during in vivo degradation. After maximum 10 days, animals were killed and necropsy was performed. Tissues were compared between the stented groups as well as between the non-stented contralateral ureters and stented ureters in each group. Biocompatibility was assessed by histopathological grading. Results: In all cases, the BUS was only visible during the first 24 h on X-ray, and in all cases the BUS was completely degraded in urine after 10 days, as confirmed on necropsy. During the degradation process, the mechanical properties of the BUS decreased, while the commercial ureteral stents remained constant. At all time-points after stent insertion, the level of hydronephrosis was minimal. Overall, animals stented with BUS had an average grade of hydronephrosis which was lower compared to the controls. The BUS showed better pathological conditions, and hence better biocompatibility when compared with commercial stents. Conclusions: Notwithstanding the limitations of the present study, the in vivo testing of our novel natural origin polymer-based BUS suggests this device to feature homogeneous degradation, good urine drainage, and high biocompatibility. Next steps will be to increase its stability, and to improve the radiopacity without compromising its degradation. Ultimately, clinical studies will be required to determine the safety and feasibility of its use in humans.

© 2017 American Pharmacists Association® A drug-eluting biodegradable ureteral stent (BUS) has been developed as a new approach for the treatment of urothelial tumors of upper urinary tract cancer. In a previous work, this system has proven to be a good carrier for anticancer drugs as a potential effective and sustainable intravesical drug delivery system. BUS has revealed to reduce in 75{%} the viability of human urothelial cancer cells (T24) after 72 h of contact and demonstrated minimal cytotoxic effect on human umbilical vein endothelial cells (HUVECs) which were used as a control. In this work, we studied the permeability of the anticancer drugs, such as paclitaxel and doxorubicin, alone or released from the BUS developed. We used 3 different membranes to study the permeability: polyethersulfone (PES) membrane, HUVECs cell monolayer, and an ex vivo porcine ureter. The ureter thickness was measured (864.51 $μ$m) and histological analysis was performed to confirm the integrity of urothelium. Permeability profiles were measured during 8 h for paclitaxel and doxorubicin. The drugs per se have shown to have a different profile and as expected, increasing the complexity of the membrane to be permeated, the permeability decreased, with the PES being more permeable and the ex vivo ureter tissue being less permeable. The molecular weight has also shown to influence the permeability of each drug and a higher percentage for doxorubicin (26{%}) and lower for paclitaxel (18{%}) was observed across the ex vivo ureter. The permeability (P), diffusion (D), and partition (K d ) coefficients of paclitaxel and doxorubicin through the permeable membranes were calculated. Finally, we showed that paclitaxel and doxorubicin drugs released from the BUS were able to remain in the ex vivo ureter and only a small amount of the drugs can across the different permeable membranes with a permeability of 3{%} for paclitaxel and 11{%} for doxorubicin. The estimated amount of paclitaxel that remains in the ex vivo ureter tissue is shown to be effective to affect the cancer cell and not affect the noncancer cells.

© 2017 Elsevier B.V. The preparation of natural deep eutectic solvents (NADESs) from cheap and readily available raw materials is reported. In this work, we have considered mixtures of choline chloride (CC) or betaine (Bet) with 3 sugar molecules (glucose (Glu), xylose (Xyl) and sucrose (Suc)) and 2 carboxylic acids (citric (CA) and tartaric (Tart) acids). The formation of NADESs was investigated by polarized optical microscopy (POM) and differential scanning calorimetry (DSC). The CC mixtures give origin to NADESs for 1:1 M ratio with the sugar molecules and for 2:1, 1:1 and 1:2 with the carboxylic acids, while Bet mixtures only formed NADES with the carboxylic acids. The effect of water content (up to 5{%} (wt.{%})) and temperature in conductivity and rheology were characterized. The NADESs were found to be non-thixotropic, Newtonian liquids with high viscosity, decreasing with increasing temperature and water content. The conductivity is limited by charge carrier mobility, thus increasing with water content and temperature.

© 2017 Elsevier B.V. Porous polymeric materials are studied in tissue engineering, because they can act as support for cell proliferation and as drug delivery vehicles for regeneration of tissues. Hydrogel foaming with supercritical CO 2 is a suitable alternative for the creation of these structures, since it avoids the use of organic solvents and high temperature in the processing. In this work, $\beta$-glucans were used as raw materials to create hydrogels due to their easily gelation and biological properties. The enhancement of porosity was generated by a fast decompression after keeping the hydrogels in contact with CO 2 . The effect of the processing conditions and type of $\beta$-glucan in the final properties was assessed regarding morphological and mechanical properties. Finally, the ability of these materials to sustainably deliver dexamethasone was evaluated. The scaffolds had good morphology and provided a controlled release, thus being suitable to be used as scaffolds and drug delivery vehicles.

Fast-dissolving delivery systems (FDDS) have received increasing attention in the last years. Oral drug delivery is still the preferred route for the administration of pharmaceutical ingredients. Nevertheless, some patients, e.g. children or elderly people, have difficulties in swallowing solid tablets. In this work, gelatin membranes were produced by electrospinning, containing an encapsulated therapeutic deep-eutectic solvent (THEDES) composed by choline chloride/mandelic acid, in a 1:2 molar ratio. A gelatin solution (30{%} w/v) with 2{%} (v/v) of THEDES was used to produce electrospun fibers and the experimental parameters were optimized. Due to the high surface area of polymer fibers, this type of construct has wide applicability. With no cytotoxicity effect, and showing a fast-dissolving release profile in PBS, the gelatin fibers with encapsulated THEDES seem to have promising applications in the development of new drug delivery systems.