## 2 A General Summary of Food Biocompatible SLNs and NLCs: Composition and Preparation Methods
### Structural Composition
#### 2.1.3 Preparation Methods  
All procedures for the preparation of nanoemulsions are potentially suitable for SLNs and NLCs, provided that all the procedures are performed at a temperature above the melting temperature of the lipid matrix of the system. Such preparation procedures include high pressure homogenization, solvent emulsification-evaporation, solvent emulsification-diffusion, solvent displacement, ultrasonication, micro-emulsification, spontaneous emulsification, and phase inversion [10]. Many procedures involve the use of organic solvents, and are thus inappropriate to be used for the fabrication of food-grade SLNs or NLCs. Furthermore, preparation procedures that require the use of high concentrations of synthetic emulsifiers and/or co-emulsifiers are not compatible with the food industry. On the other hand, scale-up (like scalability at the industrial level) is also a parameter used to determine appropriate preparation methods for SLNs and NLCs. High pressure homogenization (HPH) and microfluidization have widely been considered the most effective techniques for fabricating SLNs and NLCs, since related devices with different capacities are commercially available. As such, they have been widely applied in the food industry [18; 19; 22; 28]. HPH has been used to produce nanoemulsions for parenteral nutrition; its scaling up, in most cases, has not presented any problems [22]. There are two homogenization approaches (hot and cold) used in the production of SLNs (Figure 3a). In both processes, the melting of lipids at high temperatures, followed by the incorporation of bioactives in molten lipids, is a prerequisite for production of SLNs. The hot HPH process is suitable for the loading of heat-stable bioactives in SLNs; this is generally carried out at temperatures above the melting temperature of the lipid matrix. At first, the bioactive-loaded lipid melt is added into a hot aqueous solution containing emulsifiers and/or co-emulsifiers. The mixture is then subjected to a shearing homogenization to form a coarse emulsion (at the same temperature as above). The coarse emulsion is further homogenized at high pressures, resulting in the formation of nanoemulsions. If necessary, the HPH treatment can be repeated several times to ensure that the resultant emulsions are at the nanosized scale. Lastly, SLNs are formed by cooling hot nanoemulsions to room temperature or below. As for the cold HPH process, it is more suitable for the encapsulation of heat-labile bioactive compounds [19]. In this case, the molten lipid phase, with bioactivesincorporated, is rapidly cooled with liquid nitrogen or dry ice, which ensures that all the loaded bioactives can be evenly distributed in the solid lipid matrix. Then, the solid matrix is mechanically ground into microparticles, with sizes in the range of 50-100 \(\upmu\)m. After that, the microparticles are dispersed in a cold emulsifier solution to form a suspension. The suspension is further treated by HPH at room temperature or below, to form a dispersion containing SLNs. Aside from HPH, SLNs and NLCs can also be obtained using other high-energy-input emulsification techniques, e.g., microfluidization and ultrasonication [18; 19; 28]. In these cases, a pre-emulsification through a shearing process at temperatures above the melting temperature of lipid matrix is still a prerequisite for successful production of SLNs or NLCs. In contrast, the lipid nanoparticles formed by microfluidization would be much more homogeneous and finer than those made by ultrasonication. More importantly, industrial-scale microfluidizers are commercially available; thus, microfluidization exhibits great potential for use in the preparation of SLNs or NLCs. In addition, SLNs or NLCs can be fabricated by many low-energy emulsification processes that do not require significant energy to reduce the emulsion size [28].