Recent trends in solubility and bioavailability enhancement using natural deep eutectic solvents: current challenges and future perspectives

The therapeutic potential of bioactive compounds is determined by their solubility and bioavailability. In essence, various approaches have been explored to improve solubility and bioavailability for low water-soluble drugs. Organic solvents are extensively used to solubilize poorly water soluble drugs. Despite their advantages in drug solubilisation, organic solvents have notable drawbacks, including environmental impact, toxicity and high cost. Consequently, there is an increasing demand for green solvents that are safe for the environment and humanity. Natural Deep Eutectic Solvents (NDES) represent a novel category of sustainable solvents that have recently been investigated as potential substitutes for traditional solvents to increase the solubility and bioavailability of drugs and phytochemicals. In contrast to organic solvents, natural deep eutectic solvents have gained attention as environmentally friendly, biodegradable, less-toxic, easy to manufacture, and cost-effective. In this review, we shed light on the fundamental properties, preparation methods, and compositions of natural deep eutectic solvents. Importantly, we explore the recent application of NDES in enhancing the solubility and bioavailability of poorly water soluble drugs and phytochemicals, with comparisons to conventional solvents. This review underscores the suitability and potential of NDES as sustainable solvents for pharmaceutical applications. Additionally, we highlighted the health, safety, and environmental (HSE) implications of NDES, critical challenges and outlined promising directions for future research in this evolving field.