2.2.2. Nanoemulsions

Nanoemulsions are thermodynamically and kinetically stable systems with nanoscale droplet sizes (100 nm to 400 nm) [33], uniform size distribution, and physicochemical and biological properties different from those of other emulsions (> 500 nm) (Figure 3A) [36]. The small droplet size, the scarce probability of coalescence and flocculation, effective delivery of active ingredients, rapid penetration, long-lasting effects, and uniform deposition onto the skin make them suited for use in the personal care, cosmetic, and health science fields [37]. Articles on micro- and nanoemulsions are described in Table 2.

**Figure 3.** Schematic representation of AST delivery systems. (**A**) Emulsions: AST microemulsions and nanoemulsions; (**B**) particulate systems: AST microparticles and nanoparticles; (**C**) inclusion complexes: AST cyclodextrins (CDs); (**D**) films: AST polymeric films. Created with BioRender.com (accessed on 17 August 2021).

To obtain stabilized cosmetic products with anti-wrinkle, anti-aging, and humectant properties, Kim et al. [37] prepared oil/water AST nanoemulsions using glycerol esters such as glyceryl citrate, lactate, linoleate and oleate as alternative emulsifiers to the traditional hydrogenated lecithin. Nanoemulsions were studied in terms of their physicochemical properties, such as the emulsifier type and concentration, preparation conditions, and AST concentration, and were characterized by a freeze-fracture scanning electron microscope (FF-SEM), TEM, and high-performance liquid chromatography (HPLC). Nanoemulsions, with zeta potential in the range from −10 to −57 mV and an average particle size of 170 nm, were progressively more unstable with the increase in particle size when hydrogenated lecithin was used.

Hong et al. [38] prepared AST nanoemulsions that were functionalized with carboxymethyl chitosan, to investigate its effects on the droplet size, stability, skin permeability and cytotoxicity of the formulation. For this purpose, the low-energy emulsion phase inversion method was used, which, in addition to preventing AST degradation during nanoemulsion preparation, has the advantages of a low cost, high energy efficiency, simplicity of production and easy scale-up. Results showed improvement in chemical stability and skin permeability, while the small droplet size, satisfactory physical stability, and low cytotoxicity were not affected by the functionalized nanoemulsion.

In a comparative study, Shanmugapriya et al. [39] prepared uniform and stable oil/water nanoemulsions containing AST or α-tocopherol by the spontaneous and ultrasonication emulsification methods, using an experimental design for optimization. The AST-containing nanoemulsions displayed anticancer, wound healing and antimicrobial effects, which suggests their use in formulations for the treatment of skin cancer and wound healing, for example via incorporation into films. The same research group [39] used AST and α-tocopherol nanoemulsions with κ-carrageenan to verify topical wound healing effects in vitro and in vivo. Results suggested the treatment as a good alternative for wounds in diabetic cases with higher activity in a shorter time.

**Table 2.** Summary of AST emulsions delivery systems, describing the preparation technique, emulsion type, characterization and stability data, and assays (in vitro/in vivo) that were performed for each system.

