## 3 Some Key Issues on the Use of SLNs and NLCs as Oral Nanovehicles for Nutraceuticals or Bioactives
### Liposoluble Nntraceuticalticals
#### 4.1.2 Fat-Soluble Vitamins  
Vitamins are important micronutrients. They are essential to human nutrition and health, and play roles in normal metabolism, cellular regulation, growth, and development [100; 101]. There are two kinds of vitamins: water-soluble and fat-soluble. The fat-soluble vitamins include vitamin A (retinol, retinal and retinyl esters), vitamin D\({}_{2}\) (ergocalciferol), vitamin D\({}_{3}\) (cholecalciferol), vitamin E (tocopherol) and vitamins K\({}_{1}\) (phylloquinone) or K\({}_{2}\) (menaquinone). These liposoluble vitamins cannot be readily solubilized in the gastrointestinal tract, and are apt to chemical degradation under oxidative, pH, light, and heat stresses, thus exhibiting low bioavailability [100]. The use of lipid nanoparticles (SLNs and NLCs in particular) as oral nanovehicles for such liposoluble vitamins has been considered an effective strategy for improving their solubility in aqueous phase, chemical stability, epithelium permeability, and bioavailability [100]. In this regard, the EE for liposoluble vitamins (e.g., vitamin A or D) to be incorporated in such lipid nanovehicles can be close to 100% [77; 102; 103]. This is consistent with the fact that all liposoluble vitamins are very biocompatible and miscible with the lipid matrix in SLNs and/or NLCs. Vitamin D is an important fat-soluble micronutrient or nutraceutical. It mainly exists in two forms: i) vitamin D\({}_{2}\) (ergocalciferol), synthesized only by plants, and ii) vitamin D\({}_{3}\) (cholesterolferol), synthesized by the human body. In addition to the traditional role in the human bone metabolism, vitamin D is of crucial importance for the prevention of many diseases, e.g., neurodegenerative diseases, cardiovascular diseases, diabetes, and cancers [104]. The insufficient intake and deficiency of this vitamin is still a global issue, especially for infants, children, and child-bearing women [104]. As expected, both SLNs and NLCs can be applied to act as nanovhelics for vitamin D (D\({}_{2}\) or D\({}_{3}\)) [78; 79; 80; 81; 82]. The EE and LC of vitamin D in these nanoparticles are highly variable with the applied lipid composition (and type of lipid nanoparticles) and emulsification process (Table 1). [PERSON] and [PERSON] [78] evaluated the effectiveness of using tripalmitin SLNs stabilized by Tween 20 as nanovhelics for vitamin D\({}_{2}\). The SLN dispersions (5%, \(w/w\)) with the vitamin incorporated in the molten lipid were formed by an HPH process at 80 \({}^{\circ}\)C. In this work, the EE was undetermined, while the maximal LC was able to reach 15% (relative to the lipid content). Interestingly, it was indicated that increasing the vitamin-to-lipid ratio from 0% to 20% resulted in a progressive decrease, from 120 to about 65 nm, in \(z\)-average diameter of the SLNs. Accordingly, the turbidity of the dispersions were noticeably reduced [78]. The findings confirmed the high capacity of SLNs to deliver this vitamin, thus providing an alternative to milk or margarine as a source of vitamin D. If SLNs are formed using a combined solvent emulsification and evaporation strategy, instead of HPH, the LC of vitamin D in the nanoparticles can be even higher. [PERSON] et al. [79] reported that SLNs of stearic acid and beeswax blend, fabricated using the solvent emulsification and evaporation approach, exhibited an LC of 19%-350% for vitamin D\({}_{3}\) incorporation, though the EE was only in the range 43-78%. They indicated that increasing the beeswax ratio in the lipid matrix decreased the storage stability of encapsulated vitamin D\({}_{3}\), but increased its EE and release rate (in the phosphate buffer). [PERSON] et al. [80] successfully fabricated NLCs consisting of a glycerol monostearate (solid lipid) and oleic acid (liquid lipid) blend as nanovhelics for improving the stability and release behavior of vitamin D\({}_{3}\), using an HPH process. The as-fabricated NLCs had high EE values of 68-86%, with the EE decreasing with increasing vitamin D concentration.