Natural deep eutectic solvents (NADES) in drug delivery systems: Characteristics, applications, and future perspectives

Abstract

Deep eutectic solvents (DESs) are a class of low-melting mixtures formed by the hydrogen-bond interactions between hydrogen bond acceptors (HBAs) and hydrogen bond donors (HBDs) in specific molar ratios. Their unique physicochemical properties enable DESs to significantly enhance drug solubility and permeability, while also serving as carriers to facilitate efficient drug delivery. A subclass of DESs, natural deep eutectic solvents (NADESs), is found in the metabolites of natural organisms, such as plants. With low toxicity and biodegradability, NADESs possess distinct advantages for applications in the pharmaceutical field.The therapeutic efficacy of drugs is often limited by imprecise release mechanisms, leading to the metabolism or degradation of a portion of the drug before it reaches the target site, thereby reducing its effectiveness. Moreover, many drugs exhibit poor solubility and stability, resulting in low efficiency during absorption and metabolism, which further diminishing their therapeutic impact. NADESs, with their excellent tunability and biocompatibility, have demonstrated great potential in drug delivery systems.This paper first provides an overview of the fundamental characteristics of NADESs, followed by a detailed summary of recent advancements and applications of NADESs across various administration routes, including transdermal, mucosal, and inhalation drug delivery. Finally, the paper explores the prospects of NADESs in novel drug delivery systems and proposes strategies for optimizing their performance to promote clinical applications.