Deep Eutectic Solvents for Essential-Oil Delivery and Bacterial-Infected Wound Healing

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