*5.2. Surfactants*

Surfactants can be classified according to their electrical characteristics as ionic, nonionic, and zwitterionic. Most foods surfactants are ionic, such as esterified monoglycerides, which are mainly negatively charged and can form nanoemulsions using low or high energy. Non-ionic surfactants also can be used for both methods and have low toxicity and irritability, including compounds such as Tween® (condensate of sorbitol fatty acid esters and ethylene oxide) and Span® (a family of fatty acids sorbitan). On the other hand, zwitterionic surfactants contain two or more ionizable groups with opposite charges, and consequently, they can have a negative, positive, or neutral charge depending on the pH solution. For example, this group includes lecithin, a phospholipid widely used in foods [57,62].

One of the main aspects of an emulsion formulation is the choice of surfactant. The hydrophilic–lipophilic Balance (HLB) system was developed, which represents the balance of the size and strength of the polar and non-polar groups [62]. It demonstrates molecule properties as amphiphilic compounds using a numerical scale, assigning higher HLB values as the substance is more hydrophilic [62]. However, the HLB system only considers the properties of the surfactant itself. For this reason, the hydrophilic–lipophilic deviation (HLD) system is another approach to the behavior exhibited by surfactant– oil–water and usually more suitable in formulations [57,63]. In addition, proteins, polymers with amphiphilic properties, and combinations of polymers and surfactants can act as emulsifiers [64].

Studies have demonstrated the importance of modulating nanoemulsions composition and structure to achieve higher digestion and absorption in the gastrointestinal tract and to efficiently deliver compounds such as vitamins and nutraceuticals [54,58,65,66]. Therefore, the choice of emulsifier is of extreme importance since it can improve carotenoids bio-accessibility, for example. In a study performed by Yao et al. (2019) [65], the authors demonstrated the relationship between carotenoids bio-accessibility from spinach and co-ingesting with excipient nanoemulsions: nanoemulsions containing different ratios of medium or long-chain triglycerides in the oil phase composition decreased β-carotene bioaccessibility when the ratio of medium-chain triglycerides was increased. The findings were credited to the formed micelle's ability to hold the carotenoids in their hydrophobic domains.
