## 1 Introduction
A recent study reports the inclusion of LVX in nanoparticles as a promising strategy to suppress antibiotic resistance and biofilm formation in _Actinetobacter baumantii_[20]. Furthermore, the combination of nanoencapsulated oregano oil with both ciprofloxacin and gentamicin has been proposed to treat MRSA skin infections [21]. [PERSON] et al. demonstrated that nafcillin sodium- and levofloxacin-loaded poly (lactide-co-glycolide) nanoparticles coated with calcium phosphate are able to inhibit the formation of an _S. aureus_ biofilm [22]. LVX is a lipophilic compound [23] and it can be successfully encapsulated in a bioactive oil phase. Nanoemulsions (NEs) can be obtained by dispersing an oil phase in water, with droplet sizes on the order of 100 nm; NEs can be easily prepared, and the excipients used for their formulation are generally biocompatible and biodegradable. Oil-in-water (O/W) NEs have been proposed for cosmetic and drug formulations, notably for lipophilic molecules that can be incorporated and protected in the oily nanodroplets [24]. Additionally, the properties of the oil in the NEs can enhance the activity of the entrapped drug. Recently, some authors suggested the promising use of NEs against virulence factors in multidrug-resistant _S. aureus_ strains [25]. The LO unsaponifiable fraction, predominantly hydrocarbons, monoterpenes and sesquiterpen, associated with polyunsaturated fatty acids and polyphenols, seems to be the main agent of its regenerative effect at the skin level [26]. Clinical trials have demonstrated the therapeutic potential of Chios mastic. The European Medicines Agency (EMA) acknowledged the resin of _P. lentiscus_ L. (mastic) as a traditional herbal medicinal product with two therapeutic indications: mild dyspeptic disorders and skin inflammation/healing of minor wounds. In recent years, Chios mastic has been extensively incorporated into medicinal products, food supplements, and cosmetics, becoming a subject of research in the field of pharmaco-technology [27]. Moreover, several studies have highlighted the anti-inflammatory activity of the essential oil obtained from mastic resin in cases of skin irritation. Furthermore, based on the research on mastic-based liposomes conducted by [PERSON] et al., 2018, PO showed no specific toxicity at precise concentration ensuring the proliferation of keratinocytes and fibroblasts [28]. In our study, due to the wealth of bioactive molecules, especially fatty acids and phenolic compounds, which are key contributors to its numerous beneficial properties, PO could represent an appropriate candidate for developing nanocarriers to improve antimicrobial and antibioticlin activity. Herein, an untargeted metabolomic approach was performed to achieve a large coverage of phytochemicals in this complex mixture, given the high resolving power and sensitivity of the Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer coupled with electrospray ionization (ESI) [29]. This approach allows for a reliable chemical characterization of (semi) polar compounds of LO, thus offering a fast method to perform a qualitative description of the phytochemical fingerprint [30]. Van Krevelen diagrams (vKd) and a donut chart of elemental composition have supported the qualitative analysis by furnishing a graphical description of the metabolomics fingerprint. The chemical characterization of the LO proposed in this study is an essential preliminary step aimed to quali-quantitatively assess both its primary and secondary metabolome. The volatile and semi-volatile fraction of the seed LO was analyzed through static-HS-GC-MS and HS-SPME-GC-MS with the purpose to subtly determine the fingerprint of this matrix by assigning all the components of the multifaceted terpenes and sesquiterpen pattern [31]. Moreover, this study aims to design and characterize LO-based NEs, both empty and those loaded with LVX.