Production of Electrospun Fast-Dissolving Drug Delivery Systems with Therapeutic Eutectic Systems Encapsulated in Gelatin.

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.

Fractionated extraction of polyphenols from mate tea leaves using a combination of hydrophobic/ hydrophilic NADES.

A new methodology for the selective extraction of antioxidants from mate tea leaves (and decaffeinated mate tea leaves), using different natural deep eutectic systems (NADES), is reported in this paper. A fractionated extraction was carried out and the optimization of the extraction conditions such as solid/liquid ratio, temperature, time, stirring and the use of ultrasound assisted extraction (UAE) technology was performed. The results demonstrate that a sequential extraction using, in a first step, an hydrophobic system Men:Lau (2:1) and, in a second step, an hydrophilic lactic acid-based NADES, leads to two distinct extracts: the first one rich in pigments and the second one rich in polyphenols. NADES systems were able to extract 30% more of the polyphenolic components of the mate tea leaves matrices, when compared with traditional solvents/techniques. Moreover, it has been shown that the incorporation of the extract in the NADES, compared to the same extract in aqueous medium was beneficial for the stabilization of the antioxidants. It maintains their functionality at least for three months, reaching 41% more versus the extracts obtained by traditional solvents/techniques. The absence of caffeine in the extracts did not shown to have any effects on the stability results.

Therapeutic Role of Deep Eutectic Solvents Based on Menthol and Saturated Fatty Acids on Wound Healing.

The breakthroughs achieved in green solvents promote the emergence of therapeutic deep eutectic solvents (THEDES), which possess intriguing possible applications in the biomedical field. Herein, the main aim was to unravel the biomedical potential of hydrophobic THEDES based in menthol and saturated fatty acids with different chain lengths (e.g., stearic acid (SA), myristic acid (MA), and lauric acid (LA)). Our comprehensive strategy resulted in the thermophysical characterization of different formulations, which allow one to identify the most suitable molar ratio, as well as the intermolecular interactions behind the successful formation of THEDES. The evaluation of their biological performance was also performed toward bacteria and HaCaT cells. Among the different formulations of THEDES, the one based on menthol and SA establishes stronger hydrogen bonding interactions, being also the most promising formulation because it did not elicit any relevant cytotoxicity, and potentiated wound healing, while presenting antibacterial properties against Staphylococcus epidermis and Staphylococcus aureus strains, some of which were methicillin resistant. This work provides clues on the future use of THEDES based on menthol:SA in wound dressings.

Valorization of fatty acids-containing wastes and byproducts into short- and medium-chain length polyhydroxyalkanoates.

Olive oil distillate (OOD), biodiesel fatty acids-byproduct (FAB) and used cooking oil (UCO) were tested as inexpensive carbon sources for the production of polyhydroxyalkanoates (PHA) with different composition using twelve bacterial strains. OOD and FAB were exploited for the first time as alternative substrates for PHA production. UCO, OOD and FAB were used by Cupriavidus necator and Pseudomonas oleovorans to synthesize the homopolymer poly-3-hydroxybutyrate, while Pseudomonas resinovorans and Pseudomonas citronellolis produced mcl-PHA polymers mainly composed of hydroxyoctanoate and hydroxydecanoate monomers. The highest polymer content in the biomass was obtained for C. necator (62 wt.%) cultivated on OOD. Relatively high mcl-PHA content (28-31 wt.%) was reached by P. resinovorans cultivated in OOD. This study shows, for the first time, that OOD is a promising substrate for PHA production since it gives high polymer yields and allows for the synthesis of different polymers (scl- or mcl-PHA) by selection of the adequate strains.

Dissolution enhancement of active pharmaceutical ingredients by therapeutic deep eutectic systems.

A therapeutic deep eutectic system (THEDES) is here defined as a deep eutectic solvent (DES) having an active pharmaceutical ingredient (API) as one of the components. In this work, THEDESs are proposed as enhanced transporters and delivery vehicles for bioactive molecules. THEDESs based on choline chloride (ChCl) or menthol conjugated with three different APIs, namely acetylsalicylic acid (AA), benzoic acid (BA) and phenylacetic acid (PA), were synthesized and characterized for thermal behaviour, structural features, dissolution rate and antibacterial activity. Differential scanning calorimetry and polarized optical microscopy showed that ChCl:PA (1:1), ChCl:AA (1:1), menthol:AA (3:1), menthol:BA (3:1), menthol:PA (2:1) and menthol:PA (3:1) were liquid at room temperature. Dissolution studies in PBS led to increased dissolution rates for the APIs when in the form of THEDES, compared to the API alone. The increase in dissolution rate was particularly noticeable for menthol-based THEDES. Antibacterial activity was assessed using both Gram-positive and Gram-negative model organisms. The results show that all the THEDESs retain the antibacterial activity of the API. Overall, our results highlight the great potential of THEDES as dissolution enhancers in the development of novel and more effective drug delivery systems.