Using Nanoparticles to Get the Most Out of Antioxidants in Food

Keywords::

• antioxidants
• food industry
• foodstuffs
• lipid nanoparticles

In this century, science is growing at an exponential rate, and these advances have made applications possible in all sectors of industry and research. One of the major advances is the combination of interdisciplinary areas such as chemistry, physics, biology and engineering, in the well-known nanotechnology field [1].

Nanotechnology is the study of manipulating matter on the atomic and molecular scale. Generally, it deals with structures measuring between 1 and 100 nm, and includes the development of materials or components useful for a wide range of research areas [2]. The application of nanotechnology in the food industry is a new approach when compared with the biomedical and information technology industries. There are numerous opportunities for the use of nanotechnology in foodstuff, such as processing products, food security, biosecurity and innovative materials (e.g., nanoparticles) [3]. The development of nanomaterials (such as nanoparticles for bioactive loading) has mainly focused on the physicochemical protection of sensitive compounds, enhancing their stability and/or masking odor or taste [4]. The control of the release properties of certain bioactives has also received much attention in the development of functional foods, which are foods whose elements have some physiological function beyond the nutritional (such as polyunsaturated fatty acids, carotenoids, vitamins, coenzymes and polyphenols) [5,6]. Antioxidants, such as tocopherols, carotenoids and ubiquinones have been used to preserve foodstuff against deterioration, rancidity and discoloration because of their auto-oxidation properties, which are also relevant in dietary supplements. The main role of tocopherols (vitamin E) is their antioxidant properties. Vitamin E prevents oxidation of unsaturated fatty acids, phospholipids and vitamin A, and helps in maintaining cell membrane stability. It is also is essential for normal neurological function and because of its role as an antioxidant, vitamin E may also be used in cancer prevention. Tocopherols are commonly available in most of the vegetable oils and α-tocopherol has been successfully loaded in lipid nanoparticles [7,8].

Carotenoids are able to absorb light, they bind to hydrophobic surfaces, are lipophilic, easily isomerized and oxidized because they stop free radical-mediated reactions, and quench singlet oxygens. Provitamin A carotenoids exhibit health-promoting properties such as, anticancer properties, prevention of cardiovascular disease, decreased risk of cataract formation and immunoenhancement. These molecules have already been loaded in lipid nanoparticles with very high encapsulation efficiencies [9,10].

Ubiquinones are fat-soluble vitamin-like substances present in the mitochondria and are required in the last stage of aerobic cellular respiration. These molecules demonstrate preventive properties for the damage of red blood cells similar to vitamin E and selenium. Supplementation of coenzyme Q₁₀ can be provided by loading the molecule in lipid nanoparticles [11–13], and may be used in the treatment of cancer and as relief from the side-effects of cancer treatment. Coenzyme Q₁₀ is used therapeutically for treating disease, but it has also been demonstrated that low dosages of coenzyme Q₁₀ reduce oxidation and DNA double-strand breaks, and a combination of a diet rich in polyunsaturated fatty acids and coenzyme Q₁₀ supplementation leads to a longer lifespan.

These compounds therefore have great potential in food industry. However, antioxidants are susceptible to oxidation and isomerization, resulting in low oral bioavailability. An innovative approach is the use of nanoparticles in food products as an alternative to protect these molecules through the gastrointestinal tract.

The choice of antioxidant is based on its effectiveness at low concentrations, properties with respect to color, odor and taste of food, and toxicity of its metabolites. In addition, it should demonstrate biocompatibility and long-term stability in the developed product. In the development and optimization of a product, regulatory issues should be taken into account, and also the cost of production line and the preferences of the consumer. Efforts have been made towards loading antioxidant molecules in advanced nanoparticles, such as solid lipid nanoparticles (SLNs) [14], nanostructured lipid carriers (NLCs) [15], polymeric nanoparticles [16], liposomes [17] and emulsions [18].

Of particular interest are the SLNs and NLCs, defined as colloidal systems (50–1000 nm) that demonstrate excellent physical and chemical stability providing greater protection against degradation of bioactives [19]. The SLNs are produced from a solid lipid only, for example, in foodstuffs, more ‘friendly‘ lipids such as carnauba wax (plant origin) are usually selected. SLNs can also be composed of semi-synthetic lipids (e.g., Compritol^®), other waxes (e.g., bees wax [animal origin]), or even produced using highly purified lipids (e.g., tristearin). The use of tristearin demonstrates a particular limitation of SLNs; having a relatively high melting point, during storage time the lipid forms a perfect crystalline lattice with a reduced number of voids and vacancies to load the bioactives. Therefore, when the first SLNs were produced with less ‘organized/highly pure‘ lipids they revealed much better incorporation properties for bioactives than highly purified, highly crystalline lipid compounds. The NLCs were developed as second generation lipid nanoparticles, special nanostructuring of the particle matrix should lead to a crystalline lattice with many imperfections, thus providing more space to accommodate actives compared with SLNs (increased loading capacity). To create a particle matrix that is unable to form a perfect crystal, lipid molecules that are different in shape are used to produce the particle matrix. This is achieved by mixing lipids with very different fatty acid chain lengths, namely, by means of blending solid lipids with liquid lipids (oils). Useful oils are generally vegetable oils that are mainly triacylglycerols, where unsaturated fatty acids are generally esterified in the sn-2 position. Examples of those used in the food industry are the palm, peanut, cottonseed, sunflower, palm kernel, soybean, coconut and olive oils. The melting point of these lipid mixtures still needs to be much above the body temperature, in order to maintain the special properties due to the solid character of a particle matrix. When produced from white lipids, both SLN and NLC have the same white appearance as homogenized milk. When loading colored bioactives, the formulation will keep its milk-like appearence. Depending on the lipid content, their viscosity will decrease with the increasing percentage of lipid phase in the dispersion. Highly concentrated lipid nanoparticle dispersions (in general above 50%; although, depending on the lipid, some cases are even above ∼30% concentration) have the viscosity of a cream or even paste.

Advantages of lipid materials in comparison with others colloidal carriers are biocompatibility and biodegradation. The features of SLNs and NLCs for foodstuffs are related to their adhesive properties. Once adhered to the gastrointestinal wall, these particles are able to release the bioactives exactly where they should be absorbed. In addition, lipids are also known to enhance the oral absorption of several bioactives, contributing to the increased bioavailability [20]. There are even differences in the lipid absorption enhancement depending on the structure of the lipids. Medium-chain triacylglycerols are more effective than long-chain triacylglycerols. The body will take up the lipid and the solubilized bioactives at the same time. SLNs and NLCs can be obtained by different methods of production and allow the incorporation of water in the formulation, fat actives and surfactant ingredients [14]. Literature reports that SLNs were successful in protecting catalase against proteolysis, suggesting the potential application of catalase-loaded SLNs in functional food. In the supplementary diet, catalase is more effective than vitamins C and E, helping to promote good health and protect against many diseases. Another example is carotenoid, which is used as artificial coloring and as a diet supplement. This bioactive is a poorly-soluble ingredient, but when loaded in SLNs, these particles are able to protect the bioactive against degradation.

Conclusion

Nanotechnology can be considered a new technology in the area of foodstuff and the advantages and limitations of their use in industry have not been fully exploited. The major challenges include gathering information on the properties and risks of these nanomaterials, industrial-scale application and acceptance by consumers. Advantages of the use of SLNs and NLCs for foodstuffs include the possibility of drug protection from hydrolysis, as well as the increase in drug bioavailability and prolonged plasma levels. When products are to be administered orally in dry forms, capsules and tablets are the most frequently used. They are effective and demonstrate higher convenience of handling, identification and usage. Solid forms are generally more stable than their liquid counterparts and thus are preferred for bioactives of lower chemical stability, such as antioxidants. Dry powders can be taken after mixing with water or juices, but also in the form of capsules and tablets, however these are less preferred by some customers, who are unable to swallow the solid forms. The physicochemical stabilization of various labile bioactives is also another advantage, weakening or minimizing of undesired color of special bioactives as well as flavor enhancement. While some bioactive molecules, in particular if hydrosoluble, can be added directly into foods using, for example, plant extracts, lipophilic compounds cannot be easily loaded into foodstuff because of the risk of crystallization resulting in low bioavailability in the gastrointestinal tract. Since direct addition into foodstuffs also limits the product acceptance by the end-user because of the bitter taste, nanoparticles composed of lipid materials such as SLNs and NLCs will be of added value in this field of the food industry. In addition, SLNs and NLCs provide high encapsulation efficiencies for lipophilic bioactives, and improve the long-term stability of the product under storage. The coming years look promising and the authors expect to see the design of innovative functional food using lipid nanoparticles for metabolic diseases and other related disorders, for example, diabetes and obesity. Efforts will enable the development of safer, better quality products, with reduced costs and higher efficiency.

Financial & competing interests disclosure.

The authors acknowledge financial support from the FAPESP (Fundação de Amparo a Pesquisa, Process 2011/20801–20802) and from FCT (Fundação para a Ciência e a Tecnologia, Reference PTDC/SAU-FAR/113100/2009). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.