report
2.3.3.3.1 Delivery mechanisms for nutrients

Delivery mechanisms must fulfil certain criteria: protect the nutrient from the external environment (such as oxygen, light, temperature, pH, water), not affect the sensory perception of the consumer and deliver the nutrient to the appropriate part of the gastro-intestinal tract (GIT) in a form that allows it to be absorbed and utilised by the body. A further consideration is that all such materials must be food-grade, Generally Accepted As Safe (GRAS) or listed by the appropriate regulatory authority.

There are a number of platforms available for this purpose, based on natural and synthetic materials. Many of these can be formulated as emulsions or nano-emulsions (see report "Nanotechnology and Agricultural Production" for a description of emulsions). This potentially allows for multiple phases, with different components included in a single system. Critical to this is the control of interfacial properties which control the stability of droplets (either water or oil) within the emulsion. In addition, such systems must be robust enough to withstand food processing conditions, and environmental changes during distribution and handling by the consumer. Finally, one of the main obstacles to using nano-emulsions for foodstuffs is the lack of food-grade surfactants .

In many respects, the boundaries between health and food have blurred over recent years, as the food industry has adopted or adapted many of the delivery systems developed within the pharmaceutical industry, where nanotechnology enabled drug delivery and diagnostic platforms have been developed to overcome issues of protection and selective delivery.

There are several different compounds, both biogenic and synthetic which are being developed for the purpose of delivering additional nutrients within food. Table 2 summarises the most promising of these.

Table 2. Some promising nanostructured delivery systems for nutrients.

Nano-emulsions

These are generated by a variety of means including high pressure, sonication or through appropriate mixing conditions. They are stable, although will eventually separate into different phases. They consist of vesicles or particles (made from a variety of lipids and other polymers) suspended in solution. The system can be multi-phase; so oil or water phases can be encapsulated and the resultant vesicle encapsulated by still larger vesicles . As a result they offer the opportunity to deliver multiple components in a single system. For example, oil in water in water (o/w/w) emulsions consist of oil droplets within an aqueous phase, which in turn is encapsulated in a lipid or biopolymer vesicle (stabilised by surfactants) that is suspended in an aqueous medium (which can differ from that in the interior). Decreased droplet size has been shown to correlate with increased uptake into epithelium .

Nano-emulsions do not affect optical clarity and so have received much interest from the beverage industry for inclusion of nutriceuticals.

Solid lipid nanoparticles

These can be generated from micro- or nano-emulsions. Solid lipid nanoparticles (SLN) offer greater stability than emulsions, and so can be used in other processed foodstuffs. During synthesis the desired hydrophobic nutrient is uniformly distributed throughout the solid lipid core. SLNs are stabilised by a layer of surfactant molecules, and multiple layers can be created, potentially allowing for the incorporation of different nutrients. As a result of their small size, they are rapidly absorbed into the intestinal wall, with consequent release of nutrient. Important aspects to consider are choice of lipid, melt temperature, surfactants and process control as all affect stability of the SLN and its load capacity .

Liposomes

These are hollow capsules, usually formulated from phospholipids (such as phosphatidyl choline) which can be in the form of single or multiple bilayers. In all cases they have an aqueous interior which has the same composition as the medium in which the liposome was made. They can be produced by a number of methods such as ultrasonication, freeze-drying, reverse-phase evaporation, detergent depletion, membrane extrusion, high pressure homogenisation . They can be used deliver hydrophilic compounds, however as with nano-emulsions, they are not thermodynamically stable.

Liposomes have demonstrated an ability to protect labile compounds (such as vitamins) in foodstuffs from degradation44. However, they are highly unstable in low pH conditions and are therefore degraded rapidly within the stomach.

Micelles

These are droplets of aggregated surfactant, usually in aqueous liquid, such that hydrophobic chains are in the interior. This is a mature technology, which can be used to solubilise and deliver a wide variety of hydrophobic compounds, and has been commercialised by a number of different companies.

Casein

Casein is the major protein component of milk, and is a natural nano-carrier, responsible for delivering mineral nutrients such as calcium and phosphate to neonates. It naturally forms micelles (consisting of the four main caseins) which are quite stable to the different treatments used in food processing. Casein can self-assemble into nanoscale structures and encapsulate a variety of nutrients such as calcium, phosphates, other proteins and vitamins .

Whey proteins

Whey is the waste material from cheese, and is largely water, but contains some 20% of the original mass of milk protein, along with minerals and vitamins. With the advent of ultrafiltration systems, whey has become an important additive to many different foods, and is also used as a dietary supplement. The major protein component of whey is the globular protein ß-lactoglobulin. When whey protein is heated it forms hydrogels, largely as a result of ß-lactoglobulin. Nanoparticles of ß-lactoglobulin can also be produced using a desolvation method .

Another component of whey, a-lactalbumin, has been shown to form nanotubes from enzymatically hydrolysed bulk protein in the presence of suitable cations, such as calcium. These nanotubes are stable when freeze-dried and under conditions similar to pasteurisation, suggesting wide potential applications in the food industry .

Chitosan

Chitosan is a de-acetylated derivative of chitin, which is the second most abundant polysaccharide (after cellulose) and is a component of the shells of shrimps, crabs and other crustaceans. Chitosan is more water-soluble and can form gel-like nanocapsules whose properties are dictated by the concentration and molecular weight of the chitosan and the type and concentration of cross-linking agents. These particles can be generated by a number of different mechanisms including emulsification, coacervation and precipitation . It was originally developed for controlled release of drugs, however recently its applications within the food industry have received greater interest. This is primarily because of its muco-adhesiveness , which allows targeted uptake to either the mouth or intestinal epithelium.

Silicon

Silicon in the form of orthosilicic acid has been shown to be an essential trace element for human health. It has also demonstrated biocompatibility and biodegradability. Recent work has explored its use as a delivery vehicle for nutraceuticals . Mesoporous silicon is stable in acidic pH and so passes through the stomach, it is however digested within the intestine . It has been demonstrated that a variety of different nutrients can be loaded into nanoporous silicon such as vitamin E, omega oils, and lycopene51.

Other systems

Many different polymers are being evaluated as carriers for nutraceuticals. These include globular proteins such as albumin; and filamentous proteins such as zein, collagen and gelatine. Other food-grade polymers have been successfully employed as nano-emulsions to encapsulate nutrients, such as poly(D,L-lactic acid) (PLA) and poly(D,L-lactic-coglycolic acid) (PLGA) which have been used for ß-carotene . Different technologies are being employed to create these nanostructured systems including supercritical fluids , hydrogels and emulsion gels (controlled by ionic concentrations and pH) .