Deep Eutectic\nSolvents for Essential-Oil Delivery\nand Bacterial-Infected Wound Healing

Essential oils (EOs) are volatile secondary metabolites\nof natural\nplants with multitudinous pharmacological activities. However, limited\nby their properties, such as low solubility, high volatility, photothermal\ninstability, irritation, release, etc., EOs encounter significant\nchallenges in pharmaceutical applications. Deep eutectic solvents\n(DESs) have been developed for the transdermal delivery of biomolecules\nand lipid-soluble drugs. Herein, a series of DES carriers were synthesized\nto improve the undesirable properties of EOs. We first optimized the\nDESs according to solubilization and aqueous dispersity using Chimonanthus nitens Oliv. EO (COEO) as a model EO.\nThen, the EO–DES formulations were diluted to prepare optimal\naqueous EO–DES nanoformulations (AqEDs). Mechanically, hydrogen\nbonding allowed the DES to dissolve the complex components in EOs;\nmeanwhile, the interaction forces, such as π<i>–</i>π stacking and hydrogen bonding, drove the EO–DES to\nassemble into nanostructures in aqueous conditions, forming AqEDs.\nLastly, a case study demonstrated that clove EO-AqEDscould effectively\npromote methicillin-resistant Staphylococcus aureus-infected wound healing <i>in vivo</i>, along with biocompatibility.\nThis AqED strategy provides a generalized platform for solubilizing\nEOs and improving their transdermal/topical delivery.