## 3 Some Key Issues on the Use of SLNs and NLCs as Oral Nanovehicles for Nutraceuticals or Bioactives
### Poorly Soluble Bioactive Compounds
#### 4.2.1 Curcuminoids (and Curcumin in Particular)
They attributed the improved encapsulation performance at higher liquid lipid concentrations to increased imperfections within the lipid matrix, as confirmed in the DSC results [40]. The encapsulation performance of curcuminoids in NLCs is also affected by the type and concentration of emulsifiers. In curcuminoids-loaded NLCs, [PERSON] et al. [126] observed a slight, but progressive, increase in both EE and DL as the Tween 80 concentration in the aqueous phase increased from 1.0 to 7.5%. [PERSON] and [PERSON] [135] also observed a similar increase in EE with increasing Tween 80 concentration in curcumin-loaded NLCs. In contrast, very few works have investigated the maximal loading potential of curcumin in SLNs or NLCs; though, in a few reported works, the DL of curcumin reached 10% or above (relative to total lipid content; [123; 124; 126; 128]. In the case of NLCs as carriers for turmeric powder, DL values of 40-46.6% (relative to total lipid content) were reported [126]. The extremely high DL in these cases could be largely attributable to the high compatibility of the curcuminoid composition in the turmeric powder with the lipid matrix of the NLCs. The stability of curcumin is expected to be significantly improved by its incorporation into SLNs or NLCs, since the action of oxygen in the solutions is impeded. [PERSON] et al. [52] reported that only around 5% of total curcuminoids encapsulated in the lipid nanoparticles by melt homogenization degraded after 12 months of storage, and the encapsulated curcuminoids did not suffer significant degradation at physiological pHs after 8 hours of storage. [PERSON] et al. [125] also indicated that the encapsulated curcuminoids in NLCs fabricated by direct incorporation of curcuminoids in the melted lipid exhibited good physical and chemical stability, and only 9% of encapsulated curcuminoids degraded after a storage period of 40 days. [PERSON] et al. [128] reported that the curcumin encapsulated in SLNs at high DL (15%, \(w/v\); relative to the lipid content) did not suffer any significant change in EE and DL upon storage for up to 3 months. In addition to the long-term storage stability, the encapsulated curcumin also exhibited good photo- and pH-stability [128]. When curcumin-loaded lipid nanoparticles can be administered orally or intragartically [127; 130], they generally suffer in the digestion and adsorption process. During the gastric and intestinal digestion in the presence of digestive enzymes (e.g., lipases), encapsulated curcumin may be released into the digestive fluids. [PERSON] et al. [126] confirmed that, during in vitro simulated digestion experiments, around 95% of the total curcuminoids encapsulated in the NLCs were released during the simulated intestinal digestion, while it less than 2% were released during simulated gastric medium. [PERSON] et al. [127] further indicated that, after the mouth and stomach digestion, the particle sizes of all test SLNs were nearly unchanged (except for the sample suffering serious aggregation during digestion). Additionally, after full gastrointestinal digestion, the zeta potential of SLNs significantly decreased in magnitude and the particle size increased. The release patterns of curcumin in SLNs and NLCs, as a function of digestion time, during the simulated small intestinal digestion, were consistent with the model used to describe the homogenously-incorporated drug matrix model (Figure 4a) [55; 127]. [PERSON] et al. [52] found that the release of loaded curcuminoids in NLCs was much slower than the degradation of the lipid matrix in the simulated intestinal media, and thus considered that the transfer of the curcuminoids into the intestinal media was mainly triggered by the lipid degradation, rather than their release. To date, a few works have evaluated the absorption of curcumin in the micellar form of undigested lipid nanoparticles (SLNs), using Caco-2 cell monolayers covered with an artificial mucus layer mimicking the human intestinal epithelium [55; 122; 127].