## 3 Some Key Issues on the Use of SLNs and NLCs as Oral Nanovehicles for Nutraceuticals or Bioactives
### Liposoluble Nntraceuticalticals
#### 4.1.1 Carotenoids
[49] directly applied the \(\beta\)-carotene dispersion (10% in sunflower oil) as the liquid lipid to fabricate progylene glycol monostearate (PGMS) NLCs as nanovhelics for \(\beta\)-carotene, with the aim of evaluating the feasibility of utilizing \(\beta\)-carotene-NLCs as functional ingredients in beverages. The total lipid content of the formed NLC dispersions was 10%, with the liquid lipid ratio (relative to total lipid content) increasing up to 4.5%. The results indicated that the \(\beta\)-carotene-NLC dispersions were stable after storage for 30 weeks at 4-8 \({}^{\circ}\)C, but the encapsulated \(\beta\)-carotene suffered from distinct oxidation degradation upon prolongedstorage (e.g., >10 days). The \(\beta\)-carotene stability could be greatly improved by the co-incorporation of \(\alpha\)-tocopherol in the lipid phase. A similar enhancement of chemical stability of \(\beta\)-carotene was also reported for NLCs fabricated with other lipid components or using different fabrication processes [46; 63; 64], and confirmed in SLNs [50; 51]. The encapsulation performance of \(\beta\)-carotene in SLNs and NLCs has not been thoroughly evaluated in the literature. In several cases of purified \(\beta\)-carotene to be encapsulated in NLCs, the EE of \(\beta\)-carotene considerably varied (from 16-100%) depending on the relative ratio of the liquid lipid and temperature [46; 63]. In NLCs fabricated using the solvent diffusion method, it was indicated that the oxidative degradation of encapsulated \(\beta\)-carotene was affected more significantly by the liquid lipid to total lipid ratio and temperature than the total lipid concentration and surfactant concentration [63]. [PERSON] et al. [46], interestingly, indicated that, in NLCs stabilized by high-melting lecithin, the \(\beta\)-carotene loading efficiency progressively increased from -16% to 70%, as the liquid lipid to total lipid ratio increased from 0% to 70%. Herein, an issue of \(\beta\)-carotene exclusion from the solid lipid matrix should be taken into account. [PERSON] et al. [46] demonstrated that, as the liquid lipid to total lipid ratio increased, the extent of \(\beta\)-carotene exclusion decreased, while the distribution uniformity in the lipid matrix increased. Additionally, the oxidative stability of encapsulated \(\beta\)-carotene was negatively related to the extent of the \(\beta\)-carotene exclusion. Impaired oxidative stability in encapsulated \(\beta\)-carotene by \(\beta\)-carotene exclusion from the solid lipid matrix has also been observed in SLNs, as compared with liquid lipid nanoparticles [51]. Furthermore, [PERSON] et al. [50] found that the use of high-melting lecithin as the surfactant could provide better protection against chemical degradation in encapsulated \(\beta\)-carotene in SLNs than low-melting lecithin. The observed better protection against \(\beta\)-carotene degradation, in the high-melting lecithin case, was attributed to the retarded polymorphic transition (\(\alpha\)\(\rightarrow\)\(\beta^{\prime}\) or \(\beta\)) of solid lipid crystals [50]. Perhaps, due to the occurrence of \(\beta\)-carotene exclusion in both SLNs and NLCs, the loading amount (LA) of \(\beta\)-carotene was generally low (0.1%-0.5%; relative to total lipid content) (Table 1). In a recent work addressing the in vitro digestibility and \(\beta\)-carotene bioaccessibility of SLNs, it was, interestingly, indicated that there was no direct relationship between the in vitro digestibility of solid lipids and \(\beta\)-carotene bioaccessibility [65]. Lutein is another important carotenoid, typically derived from different vegetables (e.g., spinach) and flowers. The commercial lutein product mainly comes from a few limited sources, including marigold flowers. The solubility of this carotenoid in aqueous media is very low, thus exhibiting poor oral-bioavailability; moreover, it is very unstable and apt to chemical degradation [9].