## 3 Some Key Issues on the Use of SLNs and NLCs as Oral Nanovehicles for Nutraceuticals or Bioactives
### Bioactive Absorption and Intestinal Transport
After absorption, bioactives (or drugs) can also be transported to systematic circulation by either the portal vein or the intestinal lymphatic system. In most cases, the bioactives are absorbed through the portal vein, since the rate of fluid flow in portal blood is considerably higher than that of the intestinal lymph. However, for very lipophilic drugs (or bioactives), e.g., fat-soluble vitamins, retinoids, and lycopene, they tend to associate with the lipoproteins (above) and be transported in lymph within the apolar lipid core of lymph lipoproteins [25]. Lipid nanoparticles (including SLNs and NLCs) can be directly absorbed by the epithelium cells in the enterocyte via different transport mechanisms, as shown in many cases using in vitro Caco-2 models [57; 58]. [PERSON] et al. [58] indicated that the uptake of lipid nanoparticles (as a nanocarrier) by Caco-2 cells mainly occurred via active endocytic processes--and, more specifically, via clathrin-dependent and caveolae-dependent transport mechanisms. Due to this, the incorporation of paclitaxel (a hydrophobic drug) in lipid nanoparticles greatly improved its transport across the intestinal layer. In a more recent work, [PERSON] et al. [57] compared the cellular uptake, internalization pathways and transcytosis routes through Caco-2 cell monolayers between SLNs and NLCs (with a similar size \(\sim\) 180 nm and surface charge \(-\)30 mV), and showed that NLCs had a higher cellular uptake and permeability across the barrier, while SLNs were more quickly absorbed by the cells than NLCs. Both nanoparticles were able to cross the intestinal barrier by transcellular or paracellular routes, but the transport mechanisms varied, depending on the type of lipid nanoparticles. The uptake of both SLNs and NLCs occurred mainly through a clathrin-mediated endocytosis mechanism; though in the case of SLNs, the caveolae-mediated endocytosis also played an important role in the uptake. Both the lipid nanoparticles were able to cross the intestinal barrier, predominantly through a transcellular route. NLCs were also confirmed to cross the intestinal barrier through a paracellular route, which agreed with the higher cellular uptake and permeability of NLCs [57]. Utilization of SLNs and NLCs as Nanavehicles for Encapsulation and Delivery of Hydrophobic Nutraceuticals or Bioactive Ingredients  
Although the utilization of SLNs and NLCs as delivery systems for drugs has an approximately 40-year history, the application of such lipid-based delivery systems for nutraceuticals or bioactive components in the food industry has only about 20 years. Thanks to their lipophilic nature, lipid-based nanoparticles have advantages over other colloidal systems. They are able to perform as nanovehicles for liposoluble nutraceuticals, including carotenoids, vitamins A, D and tocopherols, \(\omega\)-3 fatty acids, and essential oils, since these nutraceuticals are completely compatible and miscible with the lipid matrix. Considering that many liposoluble nutraceuticals, e.g., carotenoids and \(\omega\)-3 fatty acids, are present in liquid oil form, or within liquid oils themselves, they can be used directly as the liquid lipid to fabricate NLCs with a high encapsulation efficiency (EE) [49], or as nanovehicles for co-loading another nutraceutical [59]. SLNs and NLCs have been recognized as the most innovative and promising nanovehicles to enhance the bioavailability of poorly adsorbed drugs [16]. Thus, the incorporation of liposoluble nutraceuticals in these lipid-based nanovehicles is expected to significantly improve their bioavailability, thus facilitating their applications in food formulations. Aside from liposoluble nutraceuticals, many hydrophobic (but poorly soluble) nutraceuticals and bioactive components, e.g., curcumin or phytosterols, can also be encapsulated within SLNs or NLCs through different fabrication strategies.