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Essential oils (EOs) represent a pivotal source for developing potent antimicrobial drugs. However, EOs have seldom found their way to the pharmaceutical market due to their instability and low bioavailability. Nanoencapsulation is an auspicious strategy that may circumvent these limitations. In the current study, lemongrass essential oil (LGO) was encapsulated in zein-sodium caseinate nanoparticles (Z-NaCAS NPs). The fabricated nanocomposite was characterized using dynamic light scattering, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and transmission electron microscopy. The antimicrobial activity of LGO loaded NPs was assessed in comparison to free LGO against Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, and Klebsiella pneumoniae. Furthermore, their antibacterial mechanism was examined by alkaline phosphatase, lactate dehydrogenase, bacterial DNA and protein assays, and scanning electron microscopy. Results confirmed the successful encapsulation of LGO with particle size of 243 nm, zeta potential of – 32 mV, and encapsulation efficiency of 84.7%. Additionally, the encapsulated LGO showed an enhanced thermal stability and a sustained release pattern. Furthermore, LGO loaded NPs exhibited substantial antibacterial activity, with a significant 2 to 4 fold increase in cell wall permeability and intracellular enzymes leakage versus free LGO. Accordingly, nanoencapsulation in Z-NaCAS NPs improved LGO physicochemical and antimicrobial properties, expanding their scope of pharmaceutical applications. [ABSTRACT FROM AUTHOR]

[Display omitted] • Thyme essential oil (TEO) was encapsulated in sodium caseinate (Na CAS)/gelatin nanocomposite hydrogel. • Oil-loaded Na CAS/Gelatin nanocomposite hydrogel exhibited sustained release pattern compared to free oil. • Oil-loaded Na CAS micelles exerted enhanced antibacterial activity compared to free TEO and resulted in cell membrane disruption and morphological distortion. • Fabricated nanocomposite hydrogel displayed significant in vivo wound healing potential in terms of reduced inflammation and increased re-epithelialization. Essential oils, derived from aromatic plants, exhibit various pharmacological properties. Nevertheless, their clinical applications are confronted by various limitations, such as chemical instability, low aqueous solubility, and poor bioavailability. Nanoencapsulation is one of the approaches that may circumvent these restraints. Accordingly, the present study encapsulated thyme essential oil (TEO) in sodium caseinate (Na CAS) nanomicelles and formulated a gelatin nanocomposite hydrogel, which was investigated as a drug delivery platform for in vitro antibacterial and in vivo wound healing potential. TEO loaded Na CAS nanomicelles showed particle size of 336 ± 17.35 nm, zeta potential of −44.0 mV and EE% of 75 ± 5%. The release profile of TEO loaded nanocomposite hydrogel revealed a sustained release pattern compared to TEO loaded micelles and free oil. The TEO loaded nanomicelles exhibited a significantly higher antibacterial effect than free TEO, as denoted by leakage of alkaline phosphatase and cell membrane disruptions. Furthermore, the TEO loaded nanocomposite hydrogel significantly promoted wound contraction, reduced interleukin-6, and increased transforming growth factor-β1 and vascular endothelial growth factor levels, versus control or blank hydrogel group. Hence, the present study is putting forth the fabricated nanocomposite hydrogel as a multifunctional delivery system for TEO in wound healing applications. [ABSTRACT FROM AUTHOR]