**1.4 Polymeric micelles**

*Nanoemulsions - Properties, Fabrications and Applications*

pressure homogenization, and microemulsions.

such as vitamins as no thermal stress is needed [29].

sterile particles, which is an advantage for nutraceuticals [26].

*1.3.1 Emulsion solvent evaporation method*

*1.3.2 High-pressure homogenization*

*1.3.3 Microemulsions*

thermodynamically stable [32].

bioactives, and thus care should be taken to employ techniques that will retain their activity during formulation. The most widely used techniques to prepare lipid nanoparticles with vitamins are the emulsion solvent evaporation method, high-

This method is based on the dispersion of a solution of the lipid components in an aqueous surfactant solution. The lipids and the lipophilic bioactive are commonly dissolved in an organic solvent such as dichloromethane, cyclohexane, ethyl acetate, or chloroform. When the nanoemulsion is formed, the solvent is extracted or evaporated, and the droplets start to solidify until solid lipid nanoparticles encompassing the active are formed. The solvent can be evaporated by agitation, rotary evaporation, or spray-drying [28]. The emulsion solvent evaporation method offers a great advantage for encapsulating actives that are highly sensitive to heat

This technique involves the preparation of a pre-emulsion, which is then passed under high pressure (100–2000 bar) through a homogenizer valve. The pre-emulsion generally composes a lipid phase and an aqueous phase containing a surfactant. The fluid is accelerated in a very short distance in the homogenizer, reaching a high speed. The lipid substances are then divided into small droplets by the shear stress forces. This technique may produce particles with low encapsulation efficiency for hydrophilic substances due to the drug migrating to the external aqueous phase during particle formation. However, lipophilic actives can be encapsulated at high dosage [30, 31]. The technique is also ideal for the production of large quantities of

Microemulsions are clear, thermodynamically stable, and isotropic liquid mixtures of oil, water, and surfactant and almost always co-surfactant as well. The droplet size in the dispersed phase of the microemulsion is less than 100 nm. The droplets are formed by the drastic cooling of a microemulsion mixture to solidify the droplets and create particles loaded with the bioactive. The preparation of microemulsions does not require much energy to form and is thus recommended for actives that are highly sensitive to shear forces or thermal stress as is the case with most vitamins [29]. Other advantages of microemulsions include the use of bioactive compatible ingredients and the enhanced stability of formulations, as they are

After preparation, lipid nanoparticles can be stored as nanosuspensions in the medium they were formed, or dry particles can be obtained using either freezedrying or spray-drying [25]. In some instances, aggregation of particles may occur due to the drying process. In these instances, an adequate amount of cryoprotectant

There has been an increasing awareness of maintaining personal health by balanced nutrition and the intake of nutraceutical supplements. Due to the challenges faced with the stability of nutraceuticals, lipid formulations have been sought to

can be added to prevent or minimize aggregation of the particles [30].

*1.3.4 Lipid nanoparticles for the delivery of vitamins*

**36**

Polymeric micelles are formed from block copolymers that have amphiphilic character. Amphiphilic polymers are copolymers composed of hydrophilic ("waterloving") and hydrophobic ("water-hating") parts [40]. They normally form spontaneously under certain concentrations and temperatures in a given media [41]. The concentration at which these micelles are formed is known as critical micelle concentration (CMC), while the temperature at which this micelle exists is called the critical micellization temperature (CMT) [41]. Hydrophobic blocks of amphiphilic polymers form the core of the micelle, while the hydrophilic blocks form the shell [42, 43]. They can be utilized as drug carriers, by incorporating the poorly soluble nonpolar substances within the micellar core and polar substances on the micellar shell (by adsorption); substances with intermediate polarity are distributed between the core and shell [41, 44]. These properties enable these systems to incorporate poorly water-soluble drugs in the micellar core by physical interaction or by chemical conjugation leading to higher solubility extents [43], to protect the drugs or sensitive substances from premature degradation and also reduce the toxicity of the drug [42]. When compared to conventional micelles, polymeric micelles have lower CMCs values and are more stable even at concentrations below CMC [41]. This behavior stems from the slower rate of dissociation that depends on the molecular weight and hydrophilic-hydrophobic balance of the polymer as well as the properties of the drug incorporated into the core [43].

### **1.5 Supercritical fluid technology**

The methods discussed in the preceding sections involve the use of organic solvents, which could impart residual moisture of organic solvents on the produced nanoparticles. Supercritical fluid technology, on the other hand, utilizes the CO2, which often

produces nanoparticles or microparticles without any trace of solvent, thus high purity. CO2 is a cheaper fluid, nontoxic, and non-flammable. Its low critical temperature of 31.1°C makes it an ideal fluid for sensitive or thermally labile materials. An active ingredient is regarded to be in a supercritical state if its temperature and pressure are above its critical values. Based on the solubility of active ingredient in CO2 (or any inert gas) fluid, particles can be formed by using two approaches as depicted in **Figure 5**: (a) rapid expansion of supercritical solution (RESS) and (b) rapid expansion of supercritical solution into a liquid solvent (RESOLV) [45]. In order to perform RESS, high solubility in the supercritical fluid is required. However, some of the active nutraceutical ingredients are organic polar compounds. CO2, due to its low polarity, is not a proper fluid for these materials. The nutraceutical ingredients are ideal for RESOLV. In RESOLV, an organic solvent is required to dissolve the vitamins expanding in the SCF.

As discussed in Section 2.3, solid lipid nanoparticles are spherical nanoparticles produced from solid fat. Instead of melting the lipids in an appropriate organic solvent, vitamin B2 was encapsulated in SNL using SCF [46]. The lipids are saturated with CO2 in order to decrease the melting point. However, Couto and colleagues modified the SCF, in which the lipid, bioactive, and surfactant mix expanded with CO2 was decompressed into a water stream containing a stabilizer. Vitamin B2, the hydrophilic bioactive, was encapsulated in fully hydrogenated canola oil (the solid lipid), using sodium lauryl sulfate as surfactant and polyethylene glycol as stabilizer. Vitamin B2 participates in a range of redox reactions central to human metabolism, and its deficiency has been linked to fetal developmental abnormalities and deficiencies in the production of red blood cells. Due to its hydrophilic nature, it is easily absorbed, but it is not stored in the body, leading to the need for

#### **Figure 5.**

*A Schematic representation of particle formation by rapid expansion of supercritical solution. In conventional RESS, blank particles are formed dissolving the solute, that is, polymer in a supercritical fluid to form a solution. This is followed by the rapid expansion of the solution across an orifice or a capillary nozzle into ambient air. The high degree of supersaturation, accompanied by the rapid pressure reduction in the expansion unit, ideally results in homogenous growth of particles and, thereby, the formation of well-dispersed particles. However, results obtained from mechanistic studies of different model solutes for the RESS process indicate that both nanometer- and micrometer-sized particles are usually present in the expansion unit [46].*

**39**

provided the original work is properly cited.

\*Address all correspondence to: lebo.seru@nwu.ac.za

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

1 Department of Chemistry, School of Physical and Chemical Sciences, North-West

2 Polymer and Composites, CSIR Materials Science and Manufacturing, Pretoria,

and Lesego Tshweu2

\*, Bathabile Ramalapa<sup>2</sup>

*Nanoformulated Delivery Systems of Essential Nutraceuticals and Their Applications*

sustained release can be obtained and its absorption can be slowed down.

replenishing its levels every day. By encapsulating it in SLN, it is anticipated that a

Numerous delivery systems such as nanoemulsions, microemulsions, liposomes,

lipid nanoparticles, polymeric micelles, and nanoparticles have been reported extensively for encapsulating nutraceuticals especially liposoluble vitamins. The lipid-based nanoformulations were highly recommended by various studies as compared to others due to their better absorption when ingested, improved stability, and low degradation in the gastrointestinal tract. However, more efforts need to be focused on their toxicity and regulatory issues for the faster development of industrially processed nanoformulated nutraceuticals from the lab-scale research discoveries. It is widely anticipated that over the next couple of years, nanoformulated delivery systems of essential nutraceuticals will continue to evolve and many novel food products are expected to be used with an enormous positive impact on

*DOI: http://dx.doi.org/10.5772/intechopen.86170*

addressing malnutrition challenges in children.

**2. Conclusions**

**Author details**

South Africa

Lebogang Katata-Seru1

University, Mmabatho, South Africa

replenishing its levels every day. By encapsulating it in SLN, it is anticipated that a sustained release can be obtained and its absorption can be slowed down.
