## 2 A General Summary of Food Biocompatible SLNs and NLCs: Composition and Preparation Methods
### Structural Composition
#### 2.1.2 Emulsifiers and Co-Emulsifiers  
Choosing an appropriate emulsifier (or surfactant) or emulsifier combination, as well as an appropriate emulsifier concentration, is of crucial importance for the production of SLNs [10]. At high temperatures above the melting temperature of the lipid matrix, the role of emulsifiers is to coat and stabilize the interface between molten lipid droplets and aqueous phase, thus facilitating the formation and stabilization of nanosized emulsions, especially those formed by high-temperature-homogenization (HPH) techniques. Except for lecithins, which are phospholipids, most emulsifiers (surfactants) are derived from mono- and diacylglycercends or from alcohols. Food grade emulsifiers mainly include mono- and diacylglycercends, phosphateal mono- and diacylglycercends, propylene glycol esters, sorbitan esters, sucrose esters, polyglycerol esters, and lactate esters [19]. Many non-ionic emulsifiers, e.g., Tweens 20, 60 and 80, have been widely applied in stabilizing nanoemulsions via high or low energy methods, thanks to their high interfacial activities. Soy or egg lecithins (as representative zwitterionic emulsifiers) are also widely used in food formulations. For better formation and stability of nanoemulsions, a combination of nonionic and ionic emulsifiers may be used, since the presence of a certain concentration of ionic emulsifiers can produce a repulsive interaction between droplets, thus favoring emulsion stability. Natural lecithins are inefficient when used as the sole emulsifier to stabilize nanoemulsions; however, they might be efficient in combination with co-emulsifiers [10]. Co-emulsifiers, e.g., alcohols and short chain organic acids, can be used to improve the emulsification efficiency of some emulsifiers through increased flexibility of the interface of the emulsified systems. The crystallization and oxidation of lipids in the nanoemulsions (or their SLNs or NLCs) stabilized by emulsifiers (and/or co-emulsifiers) may be affected by the type and concentration of emulsifiers (and/or co-emulsifiers). At higher concentrations of emulsifiers, nanoemulsions with smaller sizes are favorably formed. As a result, the interactions between lipid molecules and different functional groups of emulsifiers increase, thus modifying the crystallization kinetics and crystal polymorphs of lipids [20]. For instance, the use of high-melting-temperature lecithins as emulsifiers delayed the polymorphic transition from the metastable \(\alpha\)-form to the more stable \(\beta\)-form in SLNs with tristearin as the core [29] and inhibited the oxidation of omega 3 (\(\omega\)-3) fatty acids--which were used as the liquid lipid in NLCs that were mainly composed of tristearin [30]. Considering that many synthetic emulsifiers used in the production of SLNs (or NLCs) have potential health risks, e.g., cytotoxic effects [31], a need has arisen, in recent years, to develop more food biocompatible SLNs and NLCs using natural polymers (e.g., proteins, polysaccharides, or their complexes) to partially or completely substitute synthetic emulsifiers. Dr. [PERSON]'s research group from the University of Connecticut made some interesting observations about the strategy and effectiveness of fabricating oral SLNs and/or NLCs, with Compritol ATO 888 (glycerol behenate) as the lipid phase, using proteins and/or polysaccharides as emulsifiers or stabilizers to partially or completely substitute small-molecular-weight emulsifiers [32; 33; 34; 35]. For example, they reported a novel strategy to prepare small and homogeneous SLNs using a combination of sodium caseinate and Tween 80 as the emulsifier and pectin as the coating polysaccharide. They demonstrated that Tween 80 (0.15%, \(w/v\)), together with caseinate (0.15%, \(w/v\)), was effective, utilizing it to obtain stable SLNs with a high loading capacity for curcumin [32]. The polysaccharide-coated SLNs were confirmed to exhibit exceptional gastrointestinal (especially stomach) stability and controlled release behavior (of encapsulated curcumin) [32].