Deep Eutectic Solvents: An Eco-friendly Design for Drug Engineering.

Invited for this month's cover, the researchers from UTCBS and CiTCoM from Université Paris Cité (Paris, France), as well as Materia Nova (Mons, Belgium). The image emphasizes the deep eutectic solvent preparation thanks to hydrogen bond acceptor and donor interactions for drugs formulation and therapeutic applications. The Review itself is available at 10.1002/cssc.202300669.

Deep Eutectic Solvents: An Eco-friendly Design for Drug Engineering.

In the spirit of circular economy and sustainable chemistry, the use of environmentally friendly chemical products in pharmacy has become a hot topic. In recent years, organic solvents have been the subject of a great range of restriction policies due to their harmful effects on the environment and toxicity to human health. In parallel, deep eutectic solvents (DESs) have emerged as suitable greener solvents with beneficial environmental impacts and a rich palette of physicochemical advantages related to their low cost and biocompatibility. Additionally, DESs can enable remarkable solubilizing effect for several active pharmaceutical ingredients (APIs), thus forming therapeutic DESs (TheDESs). In this work, special attention is paid to DESs, presenting a precise definition, classification, methods of preparation, and characterization. A description of natural DESs (NaDESs), i. e., eutectic solvents present in natural sources, is also reported. Moreover, the present review article is the first one to detail the different approaches for judiciously selecting the constituents of DESs in order to minimize the number of experiments. The role of DESs in the biomedical and pharmaceutical sectors and their impact on the development of successful therapies are also discussed.

Designing fisetin nanocrystals for enhanced in cellulo anti-angiogenic and anticancer efficacy.

We report the formulation, characterization, colloidal stability, and in vitro efficiency of Fisetin nanocrystals stabilized by poloxamer P407. Such nanocrystals present a nanometer scale (148.6 ± 1.1 nm) and a high homogeneity (polydispersity index of 0.17 ± 0.01), with a production yield of 97.0 ± 2.5%. The engineered formulations of nanocrystals suspension (pH of 7.4 ± 0.1), stabilized via steric repulsion, are stable for several days in aqueous environment (Milli Q water, NaCl 10 mM or mannitol 5% w/v), for few days in HEPES buffered saline (HBS) (20 / 150 mM) under sink conditions, and in culture medium. After freeze drying in 5% w/v mannitol, the nanocrystal formulations can be stored at -80 °C for at least 120 days. Drug release experiments displayed a 98.7 ± 5.1% cumulative release over 3 days in HBS. Compared to the free drug, the nanocrystal formulations showed an improved cytotoxicity highlighted by the decrease of the half maximal inhibitory concentration for both murine Lewis lung carcinoma (3LL) and human endothelial (EA.hy926) cell lines. In addition, after incubation with Fisetin nanosuspensions, significant changes in the cell morphology for both cell lines were observed, showing an improved anti-angiogenic effect of nanocrystals formulation compared to the free drug. Overall, Fisetin formulated as nanocrystals showed enhanced biopharmaceutical properties and in vitro activity, offering a wide range of indications for challenging applications in the clinic.