## 3 Some Key Issues on the Use of SLNs and NLCs as Oral Nanovehicles for Nutraceuticals or Bioactives
### Liposoluble Nntraceuticalticals
#### 4.1.1 Carotenoids
Few works have successfully developed NLCs as nanovhelics for improving the stability and sustained release behavior of lutein [59; 66; 67]. Astonishingly, all such works applied the same commercial lutein product (20%, in corn oil) from the same company, confirming the difficulty of utilizing this carotenoid in food and pharmaceutical formulations. A maximum LC of about 3% (relative to total lipid content) with EE of \(\sim\)85% was obtained for NLCs fabricated by hot ultrasonication using lutein oleoresin (20%, in corn oil) as the liquid lipid [66]. The size of fabricated lutein-NLCs was dependent on the ultrasonication duration and the lutein loading amount. It was also confirmed that the incorporation of the lutein oleoresin led to the formation of an imperfect crystalline lattice [66], which was favorable for lutein loading in the lipid matrix. Lutein NLCs can also be fabricated using medium-chain triglycerides (MCT) or \(\omega\)-3 fatty acids as the liquid lipid, and in these cases, the lutein oleoresin was well mixed with the liquid lipid [59; 67]. The encapsulated lutein in these nanoparticles exhibited better protection against UV degradation and greater free radical scavenging ability, as well as a more sustained release behavior (Table 1). In more recent years, interest in the development of SLNs or NLCs as nanovhelics for lycopene, astaxanthin and bixin has increased [68; 69; 70; 71; 72; 73; 74; 75; 76; 77; 78; 79]. These carotenoids possess many outstanding beneficial health effects, exhibiting great potential for application in the formulations of health-related products. Lycopene, widely present in tomato, watermelon, and pink grapefruit, is one of the most potent natural antioxidants [99]. It is an acyclic open-chain unsaturated carotenoid with 11 conjugated double bonds, having a very high lipophilicity (with a log \(p\) value of 17.64). This carotenoid is insoluble in water (its solubility in oil at ambient temperatures is also low) and sensitive to oxidants, light, and heat, thus leading to low bioavailability [70]. [PERSON] and [PERSON] [68] selected orange wax and rice bran oil (with great potential to solubilize lycopene) as the solid and liquid lipids, and successfully fabricated NLCs as nanovehicles for lycopene via a hot HPH method, with a very high EE of 100% and LC values of 0.1-1.0% (relative to total lipid content). The encapsulation in the NLCs improved the chemical stability against degradation of lycopene after long-term storage, up to 3 months [68]. Using a similar fabrication process, [PERSON] et al. [69] and [PERSON] et al. [70] implemented the high-performance nanoencapsulation of lycopene in SLNs and/or NLCs, with maximum EE and LC values reaching up to 98% and 5.5%, respectively. As expected, the EE of NLCs was significantly higher than that of SLNs [70]. The feasibility of such lycopene-NLCs or -SLNs to be applied in orange drinks was explored, and it was indicated that the addition of encapsulated lycopene facilitated the solubilization of this nutraceutical in aqueous samples [70]. Bixin is another naturally occurring carotenoid. It has extremely low aqueous solubility, but good solubility in oil [9]. Utilizing the high potential of bixin to be well mixed with the lipid phase, [PERSON] et al. [76] efficiently encapsulated this carotenoid in SLNs using a hot melt-emulsification process, with EE > 99% and maximum LC value up to 18% (relative to total lipid content). They demonstrated that the nanoencapsulation of bixin in the SLNs significantly increased the in vivo hepatoprotection against paracetamol-induced injury in animal experiments. The high EE encapsulation of bixin was confirmed in polymer-coated SLNs fabricated through a spontaneous emulsification process [74; 75], wherein it was also confirmed that the nanoencapsulation improved the photo- and oxidative stability of bixin. Astaaxanthin is a xanthophyll carotenoid, found in aquatic animals (e.g., crabs and salmon) and mainly produced by microalgae [71].