## 3 Some Key Issues on the Use of SLNs and NLCs as Oral Nanovehicles for Nutraceuticals or Bioactives
### Liposoluble Nntraceuticalticals
#### 4.1.3 Omega-3 Polyunsaturated Fatty Acids (\(\omega\)-3 PUFAs)  
The very long chain \(\omega\)-3 PUFAs, e.g., eicosapentaenoic acid (EPA) and docosahexaenoicenoic acid (DHA), in the form of fish oils and \(\alpha\)-linolenic acid (ALA) from flaxseed oil, have been widely accepted as important parts of modern human nutrition, thanks to their health-promoting effects on cardiovascular diseases, inflammatory diseases, diseases in metabolism, diabetes, cancers, brain diseases, and neurological disorders [112, 113]. The \(\omega\)-3 PUFAs are not synthesized in the body, and should be included in the diet for human nutrition and health. The supplementation with \(\omega\)-3 PUFAs alters the fatty acid composition of plasma, cells, and tissues in humans, and an increased intake of \(\omega\)-3 PUFAs is known to exert beneficial effects on human health [114]. However, the application of \(\omega\)-3 PUFAs in food formulations is limited by their unpleasant flavors, a result of high oxidative instability [19]. Many effective strategies have been proposed and developed to protect \(\omega\)-3 PUFAs from oxidation during production, storage, transport, and consumption. Because \(\omega\)-3 PUFAs or \(\omega\)-3 PUFA-rich oils are liquid lipids, lipid nanoparticles (and NLCs in particular) can be considered among the most appropriate and promising nanovehicles for these bioactive ingredients. \(\omega\)-3 PUFAs can readily mix with melted solid lipids at any relative ratio, as required. Hot HPH, or hot homogenization, in combination with ultrasonication, is generally used as the emulsification process to fabricate SLNs or NLCs for \(\omega\)-3 PUFA incorporation (Table 1). Tweens or lecithin are good emulsifiers for the formation and stabilization of such nanovehicles. If the relative ratio of added \(\omega\)-3 PUFAs is low, they are generally evenly distributed in the solid lipid matrix upon cooling/solidification. [PERSON] and colleagues [86] indicated that the crystallization, polymorphic transformation, and stability of tripalmitin SLNs were highly affected by the addition of \(\omega\)-3 PUFA-rich fish oil at different ratios (relative to solid lipid content). In the absence of fish oil, the SLN suspensions tended to form a gel after the tripalmitin crystallization, attributed to the aggregation and network formation as a result of particle shape changes. The addition of fish oil to the melted lipid at a ratio of 10 wt% or above increased the stability of the corresponding SLNs to aggregation [86]. Further evidence showed that, upon increasing the fish oil ratio, the rate of \(\alpha\)- to \(\beta\)-polymorphic transitions of tripalmitin increased, and the formed crystals grew less ordered [86]. [PERSON] [87] confirmed that the encapsulation of DHA and ALA (in the form of esters) in SLNs consisting of triglycerides protected such \(\omega\)-3 PUFAs from oxidation and improved the shelf life of the corresponding formulated products. In fact, the incorporated \(\omega\)-3 PUFAs could be directly applied as the liquid lipid for the fabrication of NLCs. For example, NLCs using palm stearin and krill oil as the solid and liquid lipids had a less-ordered crystalline structure, thus exhibiting a high EE (>96%) and LC of \(\omega\)-3 PUFAs [88]. Such NLCs were demonstrated to offer good protection against UV exposure to encapsulated \(\omega\)-3 PUFAs, as well as good physical and chemical stability for long-term storage [88]. They also offered good protection to encapsulated conjugated linoleic acid against oxidation and heating [90]. Interestingly, NLCs fabricated using ALA-rich linesed oil as the liquid lipid could also act as nanovehicles for the encapsulation and delivery of poorly soluble biouctives (e.g., quercetin) and, in this case, the nano-encapsulated quercetin tended to be present in the NLCs with less ordered lipid cores (or with more relative ratios of linseed oil) [89].