## 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)  
Curcuminoids are the bioactive components of rhizomes of turmeric (_Curcuma longa_ L.; Figure 7a), accounting for 2-6% of dried rhizomes. Curcuminoids from turmeric are typically a mixture of curcumin (52-63%), demethyloxycurcumin (19-27%) and bisdemethoxy-curcumin (18-28%) (Figure 7b). Commercially-available dry turmeric extracts (standardized to 95% of curcuminoids) usually include curcumin (70-80%), demethyloxycurcumin (15-25%) and bisdemethoxy-curcumin (2.5-6.5%) [118]. To date, curcuminids in general (and curcumin in particular) have attracted extensive attention for their health benefits, including antioxidant and anti-inflammatory activities, neuroprotection, chemo- and cancer prevention, anti-cardiovascular disease, anti-obesity and anti-diabetic activities, and anti-infective properties [60; 61; 119]. Many animal and clinical studies have shown that curcumin is very safe, even at high doses (e.g., 12 g/day) in humans [120]. Despite all this, the bioavailability of curcumin is poor, due to its instability at physiological pH, insolubility in water, poor  
Figure 6: Schematic illustration for the influence of high-melting and low-melting surfactants on the nucleation and crystallization of lipid nanoparticles. Using high-melting lecithin (80H) as the surfactant, core-shell lipid nanoparticles, with \(\omega\)-3 PUFA as the cores, are formed, while, in the case of low-melting lecithin (PC75), a fraction of \(\omega\)-3 PUFA might exclude from the crystallized solid lipid matrix upon cooling. (Adapted from [30]). absorption, rapid metabolism, and rapid systemic elimination [118; 120], which greatly hinders its formulations in foods and pharmaceuticals. During the past decade, great effort has gone toward facilitating use a variety of lipid nanoparticles (SLNs and NLCs) as nanovhelics for improving the stability, bioaccessibility and/or bioavailability, and bioactivities of curcumin. Considering that curcumin is a poorly soluble and unstable polyphenol in water, it is of crucial importance to decide when and how curcumin is introduced into the system for its optimized encapsulation in the SLNs or NLCs. There are two essential modes through which curcumin is incorporated into lipid nanoparticles. Curcumin or turmeric powder (or crystals) can be directly dissolved in the melted lipid phase at high temperatures of SLNs [89; 121; 122; 123; 124], or NLCs [52; 125; 126], or solubilized in an appropriate organic solvent prior to mixing with the melted lipid phase [32; 35; 54; 127; 128; 129; 54]. When an organic solvent is involved in the incorporation of curcumin, an additional evaporation is usually needed to remove the organic solvent, before or after the melt emulsification. Table 2 presents some representative examples of using SLNs and/or NLCs as delivery systems for curcumin, or curcuminoids (turmeric extract). In most cases, the SLNs and NLCs were fabricated using a melt emulsification process followed by a cooling-induced solidification, e.g., hot HPH (high pressure homogenization), or hot shear homogenization and ultrasonication (Table 2). Figure 7: (**a**) Photographs of _curcuma longa_ L. and its dried rhizomes. (**b**) Chemical structure of curcuminoids (curcumin, demethoxycurcumin and disdemethoxycurcumin) from turmeric. \begin{table}
\begin{tabular}{c c c c c c c c c} \hline \hline \multirow{2}{*}{**Curcuminoids**} & \multirow{2}{*}{ \begin{tabular}{c} **Type of Lipid** \\ **Nanoparticles** * \\ \end{tabular}