## 3 Some Key Issues on the Use of SLNs and NLCs as Oral Nanovehicles for Nutraceuticals or Bioactives
### Liposoluble Nntraceuticalticals  
#### 4.1.1 Carotenoids  
Carotenoids are important isoprenoid pigments (from a yellow to red spectrum distribution), usually synthesized by either photosynthetic organisms or non-photosynthetic organisms (e.g., some fungi or bacteria) [96]. They are valuable liposoluble bioactive compounds with a lot of well-recognized beneficial effects on human health, including pro-vitamin A function (some of them), improvement in eye and heart health, enhancement of cognitive functions, prevention of skin cancer (or providing UV protection), immunomodulation/stimulation and reductions in risk of cardiovascular disease, cataracts, and age-related macular degeneration [9]. Most health effects of carotenoids have been associated with their potent antioxidant properties, including their free radical-quenching capacity [97]. \(\beta\)-Carotene can be converted into vitamin A in the body, while zeaxanthin and lutein seem to mainly act as antioxidants, e.g., scavenging free radicals generated in the biological system, and absorbing sunlight with particular wavelengths in the eye [97]. The chemical structure and properties of carotenoids considerably vary. Carotenoids are generally categorized into two main subgroups according to their structure and properties [9; 96; 97]. See below:  
_Nonpolar caroten_: These carotenoids have a hydrocarbon ring at one or both ends of the polyene backbone, having no oxygen or polar functional groups. They are highly liposoluble and can be accumulated in LDL or localized within the hydrophobic center of the plasma membrane. They can be further divided into two groups: pro-vitamin A (e.g., \(\beta\)-carotene and \(\beta\)-crytokanthin) and non-pro-vitamin A (e.g., lutein or lycopene). _Polar xanthophylls/phylloxanthins_: These are caroten derivatives with oxygen-containing groups, e.g., -OH (lutein), =O (canthaxanthin), a combination of -OH and =O (astaxanthin), or asters of alcohol (fucoxanthin). Xanthophylls are stronger in polarity than their parental counterparts. Carotenoids, as ingredients or additives in the food industry, are generally susceptible to light (especially UV light), oxygen, and heat [9]. The lipophilic nature of carotenoids possessing several conjugated double bonds in their polyene backbone makes them very poorly soluble in water, thus leading to low bioavailability. Thus, their ease of oxidation degradation, very low water solubility, and low bioavailability are the main factors limiting their application in food or pharmaceutical formulations. Both SLNs and NLCs have been successfully developed and utilized as safe and attractive nanovhelics for overcoming the above limitations of carotenoids [9; 98; 99]. Table 1 summarizes many previous works addressing the development and utilization of SLNs and/or NLCs as nanovhelics for different carotenoids, including \(\beta\)-carotene, lutein, lycopene, astaxanthin, and bixin. There are basically two kinds of commercial carotenoid products used in the formulation of SLNs and NLCs: high-purity carotenoid crystals and carotenoid oleoresins. Considering that the main components in many carotenoid oleoresins are liquid vegetable oils, this kind of carotenoid product can be directly used as the liquid lipid to fabricate NLCs as nanovhelics for carotenoids. \(\beta\)-Carotene is one of the most important bioactive carotenoids. It has been relatively widely investigated for its potential to be incorporated in SLNs and/or NLCs to facilitate better stability (against chemical degradation) [46; 49; 50; 51; 63; 64]. In these cases, most SLNs and NLCs can be fabricated, with Tweens (20-80) as the emulsifiers, by a melt-emulsification with high pressure homogenization (HPH) or ultrasonication, followed by a cooling-induced solidification process (Table 1). In an early work, [PERSON] et al.