Encapsulation of Monoterpene Phenols in Protein-Stabilized Nanoemulsions for Improved Wound Healing

Abstract

Monoterpene phenols have antibacterial, antioxidant, anticancer, antihypertensive, and antidiabetic properties, but their natural volatility and hydrophobicity limit their biomedical applications. In this work, we developed an oil-in-water nanoemulsion (NE) stabilized by proteins (i.e., sodium caseinate, NaCas) and polyphenols (i.e., tannic acid, TA) using phacoemulsification, where thymol (TH) was dissolved in carvacrol (CA) and the mixture was used as the dispersed phase. The NE avoids the use of traditional surfactants as the stabilizer. Amphiphilic NaCas could stabilize the NE, followed by further cross-linking of NaCas using TA. These antimicrobial agents of monoterpene phenols were efficiently encapsulated in NE to enhance their colloidal stability in aqueous solution. The resulting NE showed strong antibacterial activity, reduced inflammation ability, and improved healing of bacteria-infected wounds. TA acted as both an NE stabilizer and a synergistic agent to boost antibacterial effects and accelerate wound repair. This work demonstrates a promising strategy for delivering natural antimicrobial agents of monoterpene phenols to treat infected wounds.