## 3 Some Key Issues on the Use of SLNs and NLCs as Oral Nanovehicles for Nutraceuticals or Bioactives
### Incorporation and Release of Bioactives  
Although SLNs (and NLCs), in their early history, were developed and utilized as nanosized delivery systems in the pharmaceutical field, there has been increasing interest in their application for the encapsulation and delivery of bioactives and nutraceuticals in the food industry over the past decade. To date, a great number of bioactive compounds, with a variety of physicochemical characteristics (e.g., lipophilicity) and structures, have been successfully incorporated in SLNs and NLCs (Tables 1 and 2). These bioactive compounds can be divided into three categories: (i) lipophilic bioactives, e.g., carotenoids (\(\beta\)-carotene, lutein, lycopene, astaxanthin, bixin), tocopherols and vitamin A, \(\omega\)-3 fatty acids or fish oil, essential oils (citral and eugenol); (ii) poorly soluble bioactives, e.g., phytosterols (or its purified components), curcuminoids (curcumin), resveratrol and quercetin; (iii) water-soluble bioactives, e.g., nisin, tea polyphenols [42; 43]. The first important issue regarding the incorporation of bioactives in SLNs and NLCs is encapsulation performance and loading capacity (LC). The LC is generally expressed in percentage of loaded bioactive related to the lipid phase (matrix lipid + bioactive). In a drug case, [PERSON] et al. [11] summarized that the LC of drug in the lipid of SLN was determined by solubility of drug in molten lipid, miscibility of drug melt and lipid melt, chemical and physical structure of solid lipid matrix, and polymorphic state of lipid matrix. Thanks to their lipophilic nature, many lipophilic bioactive compounds were expected to be loaded in the lipid matrix with a high LC. In contrast, the LCs of poorly soluble or water-soluble bioactives were relatively low in these nanovehicles. On the other hand, it is worth mentioning that the solubility of bioactives in lipid melt is reduced when the molten lipid is cooled; furthermore, the crystallization of lipids occurs upon cooling, which may further decrease the retention of the bioactives in the lipid matrix. It has been well recognized that the addition of solubilizers (e.g., emulsifiers) and the presence of mono- and diglycerides in the lipid matrix are two effective strategies to promote bioactive/drug solubilization or increase the LC [11]. The improved incorporation of bioactives in SLNsand NLCs in this case was clearly associated with the inhibited lipid crystallization, and delayed polymorphic change of lipids (from unstable \(\alpha\)-form to stable \(\beta\)-form). There are basically three representative models to describe the incorporation of bioactive ingredients into SLNs: (i) homogenous matrix model (or solid solution model); (ii) bioactive-enriched shell model; (iii) bioactive-enriched core model [11,23]. The localization of bioactives in SLNs depends on the composition and nature (e.g., melting temperature) of solid lipid matrix, the solubility and miscibility of bioactives in the lipid matrix, and the preparation process (e.g., hot vs. cold homogenization). A homogenous matrix with molecularly dispersed bioactive (Figure 4a, left) is frequently observed when the cold homogenization method is applied, or when very lipophilic bioactives with high crystallization temperatures are incorporated in SLNs with the hot homogenization method. For example, \(\beta\)-carotene can be incorporated homogenously into a matrix of tristearin [23]. If the polymorphic transition of the lipids in the lipid matrix is inhibited, e.g., by addition of a stabilizing agent (e.g., high-melting lecithins), the incorporated bioactive can be evenly distributed in the \(\alpha\)-form structure of the lipid matrix, surrounded by a layer of the stabilizing agent [44]. In the hot homogenization process, the preparation of SLNs is frequently performed at least 10 \({}^{\circ}\)C above the melting temperature of the solid lipid. In general, a bioactive has greater solubility at higher temperatures.