Decitabine is a hydrophilic drug that acts by hypomethylating DNA. Decitabine is used in Europe for the treatment of acute myeloid leukemia (AML) in patients aged ≥65 years. However, it can only be administered intravenously due to very low oral bioavailability and a large distribution volume. Oral administration would allow outpatient treatment, improving quality of life and reducing treatment costs. The present study proposes to develop lipid nanocapsules (LNCs), originally designed for lipophilic drugs, to encapsulate decitabine. Two different formulations of LNCs were designed: LNCs based on a high proportion of Transcutol^® HP (THP-LNCs) and LNCs associated with a mixture of Transcutol^® HP and Tween^® 80 (THP-T80-LNCs). The second formulation had a diameter of 26.5±0.5 nm, high encapsulation efficiency (>85%), and a drug payload of 472±64 µg/mL. Decitabine-loaded THP-T80-LNC cytotoxicity was evaluated on two AML cell lines depending on their decitabine resistance: HEL (not resistant) and HL-60 (resistant). The permeability of decitabine-loaded THP-T80-LNCs was also evaluated on Caco-2 cell monolayers. Decitabine cytotoxicity against HEL and HL-60 was higher when decitabine was loaded in THP-T80-LNCs than when free. Apparent permeability on Caco-2 cell monolayers was also increased, suggesting a potentially useful formulation to increase the oral bioavailability of decitabine.

The escalating consumer demand for sustainable cosmetic ingredients poses distinct challenges, particularly concerning their stability within the final formulation. Although natural resources offer a pool of antioxidant molecules with diverse structures and polarities, achieving stabilization combined with a comprehensive antioxidant profile often proves incompatible with practical preformulation considerations. Notably, Calendula, which is rich in both polar (glycosylated flavonoids) and nonpolar (carotenoids) antioxidants, is a standout candidate. Nevertheless, the market lacks an ingredient embodying this diversity, primarily due to the limited polarity range of available usable solvents. Natural deep eutectic solvents (NaDESs) emerge as a promising solution. This study explores NaDES technology with the goal of developing a unique Calendula extract enriched in both polarities of antioxidants, a composition that is unattainable with traditional solvents. A screening of 12 NaDESs with varying polarities highlighted a NaDES based on betaine and glycerol as particularly effective, outperforming ethanol. Leveraging response surface methodology, an optimal mechanical stirring procedure for extraction was identified. The resulting extract showed a total flavonoid content of 45.42 ± 0.85 mg eq rutin/g of biomass and a total carotenoid content of 383.54 ± 4.73 µg/g biomass. It was then incorporated into a sustainable cream (1% and 10%wt) using an innovative mixing technology. The resulting creams demonstrated stability over 90 days, with no significant deviations in pH or rheological properties compared to the control, and a droplet size that was inferior to 10 µm. This study lays the foundation for pioneering natural antioxidant cocktail-loaded ingredients that are suitable for eco-friendly cosmetic formulations, substantiating the viability of integrating environmentally friendly ingredient-based solvents.