## 1 Introduction  
Carvacrol (or cynophenol) is chemically known as 5-isopropyl-2-methylphenol and is obtained from a range of aromatic plants such as oregano (_Origanum vulgar_ L.), marjoram (_Origanum majorana_ L.), black cumin (_Nigella sativa_ L.) or thyme (_Thymus vulgaris_ L.) [1,2]. Pharmacological properties, such as antioxidant [3,4], anti-inflammatory [5], analgesic [6], antitumor [7], antimicrobial [8] and antiprotozoan activities [9, 10, 11], have been attributed to this phenolic monoterpene. Its use in clinical settings is, however, compromised by its lipophilic character, resulting in low aqueous solubility, risk of oxidation and also high volatility [1]. The loading of carvacrol in lipid nanoparticles may be a promising strategy to reduce its volatility and improve its loading and bioavailability [12]. Only a limited number of studies have reported the loading of carvacrol into nanoparticles [13,14], while none has yet reported the use of nanostructured lipid carriers (NLCs) for this purpose. It has already been demonstrated that lipid mixtures have a great impact on the chemical stability of volatile compounds [15, 16, 17, 18]. Among lipid nanoparticles, NLCs are attractive colloidal carriers as they consist of nanosized particles based on a blend of solid and liquid lipids dispersed in an aqueous surfactant solution [19, 20, 21, 22]. The combined ratio between solid and liquid lipid should ensure that the produced lipid matrix melts above 40 \({}^{\circ}\)C [20,23]. Besides being biodegradable, biocompatible and of low toxicity, the major advantages of NLCs include their green nature, capacity for protecting loaded drugs/actives from chemical degradation and the provision of a controlled release of the payload [19, 24, 25, 26, 27, 28, 29]. Due to their nanostructured matrix, obtained by disrupting the crystal packing of the solid lipid by mixing it with a liquid lipid, NLCs may also offer a triggered release [30]. The degrees of crystallization and polymorphism of the NLC matrices are strongly dependent on the ratio between the solid and liquid lipids [31]. A low degree of crystallinity of the matrix is usually associated with a higher payload. The use of lipid mixtures that crystallize in a less organized matrix is linked to higher loading capacity of the nanocarriers. Several lipids excipients can be used for the production of NLCs, among which fatty acids (e.g., palmitic acid, stearic acid), fatty alcohols, mono-, di- and triglycerides, vegetable oils and waxes (e.g., carnauba wax, beeswax, cetyl palmit) are the most frequently used [32, 33, 34]. In pharmaceutical products, the employment of natural lipids is desirable [35]. Stearic acid is a saturated 18-carbon chain fatty acid that melts around 69 \({}^{\circ}\)C and is obtained from both animal and vegetal sources. It shows higher in vivo tolerability and less toxicity than fats from synthetic origin [36,37]. Beeswax is a natural fatty material with a melting point ranging between 61 \({}^{\circ}\)C and 67 \({}^{\circ}\)C, obtained from the combs of bees (_Apis mellifera_) [38,39]. Carnauba wax is a plant exudate from the Brazilian \"tree of life\" (_Copernicia cerifera_), composed almost entirely of wax acid esters of C24 and C28 carboxylic acids and saturated long-chain mono-functional alcohols, that melts around 82 \({}^{\circ}\)C, thus showing high crystallinity [40]. Stearic acid, beeswax and carnauba wax have been selected as they are considered non-toxic and \"generally recognized as safe\" (GRAS) by the US Food and Drug Administration (FDA). The use of these three fats in the production of drug delivery systems has also been previously described [41,42]. Since the majority of methods used for the production of NLCs require heating, the volatility of carvacrol may compromise the loading capacity and encapsulation efficiency of the particles for the monoterpene. The liquid status of carvacrol may also affect the structure of the lipid matrix.