**1. Introduction**

Over the past years, nutraceuticals have been explored as novel medicinal dietary products in the food and pharmaceutical industries. Dr. Stephen De Felice invented "nutraceutical" as a term in an attempt to promote medical health research [1–2]. He defined it as a food or part of a food that provides medical or health benefits, including the prevention and treatment of disease. Nutraceuticals are mostly classified into three broad groups such as dietary supplements (glucosamine, probiotics, etc.), herbals (herbs or botanical products), and nutrients (vitamins, minerals, etc.). In addition, they are consumed daily by human beings as an alternative to modern medicine, thus promoting quality life and increasing life expectancy. They have proved to offer benefits such as acting as a natural antioxidant and immune booster, fewer side effects than drugs, improved bioavailability, and long half-life [3]. The focus of the chapter will be limited to various sources of vitamins especially nanoformulated liposoluble vitamins.

Great progress toward enhancing the stability and bioavailability of vitamins, thus promoting health benefits among consumers, has been achieved by various researchers [4–6]. **Figure 1** shows a classification of vitamins according to their solubility. In the last decade, an extensive amount of research has focused on the

**Figure 1.** *Classification of vitamins with some examples of high rich foods.*

hydrophilic vitamins as compared to liposoluble ones [7, 8]. Different approaches have been explored to improve the stability and functionality of hydrophilic vitamins during product development and storage of food because of the exposure to high temperature, oxygen, and light. Novel methods were used by Alishahi et al. [9] to increase the shelf life and delivery of vitamin C using chitosan nanoparticles. In addition, three different vitamins (B9, B12, and C) were successfully encapsulated in water-soluble derivatives of chitosan biopolymer [10]. Their study showed that N,N,N-trimethyl chitosan nanoparticles can successfully be used as a stable vitamin carrier system with potential applications in foodstuffs.

**Table 1** highlights some of their health benefits and disease prevention [11–13]. Many of these vitamins have been found to have major limitations such as low chemical stability, sensitive to oxidation, high melting points, and poor solubility, thus leading to low bioavailability [14]. The inability of the human body to produce vitamins forces humans to have a balanced diet in order to intake the recommended supply of essential nutrients. The inadequate intake of various vitamins through diet may compromise biological functions such as vision, growth and development, immunological activity, reproduction, and cellular growth [11]. The application of adequate treatment can reduce the risk of development of complications related to deficiency of vitamins. Food fortification and supplements have been used as strategies to prevent vitamin deficiency. In order for nutritional supplement premixes and fortified food to work, the vitamins and micronutrients contained in these products need to remain active until consumption, which may not always be the case. Premixes and fortified foods may lose a large percentage of vitamins and micronutrient activity before consumption via processing, packaging, transportation, and storage. Therefore there is an urgent need to develop and explore cost-effective innovative approaches that will improve the stability of nutraceuticals especially liposoluble vitamins.

The delivery of vitamins using nanotechnology has attracted a number of attention recently [14] and is proposed as one of the possible innovative approaches. Numerous methods including spray-drying, spray-cooling, phase separation, emulsion systems, liposome solid lipid nanoparticles (SLN), and inclusion complexation have been proposed for the nanoformulations of liposoluble vitamins as depicted in **Figure 2**. Some of the methods including nanoemulsions, polymeric and lipid nanoparticles, etc. will be discussed in the chapter.

**33**

**1.1 Nanoemulsions**

*Nanoformulations for liposoluble vitamins [14].*

**Figure 2.**

**Table 1.**

Colloidal dispersions consisting of oil droplets dispersed in an aqueous medium in the 5–200 nm range are known as a nanoemulsion. They are isotropic systems, which are kinetically stable compared to conventional emulsions. Furthermore, they are transparent or translucent to the naked eye [15]. They have also been found to hold special characteristics such as protection from oxidant and hydrolysis in oil-in-water

*Nanoformulated Delivery Systems of Essential Nutraceuticals and Their Applications*

**Vitamin, chemical name Recommended daily intake Health benefits Deficiency**

Antioxidant, improves vision and bone growth, regulates cell proliferation, treatment of skin cancer and leukemia

bones, controls the amount of calcium in

Strengthens body's immune system, keeps blood vessels clear and flowing well, boosts the immune system, healthy skin and eyes, antioxidant

Essential for blood clotting and blood coagulation

the blood

Xerophthalmia caused by unbalanced diet or malabsorption diseases, liver disorders, night

blindness

Growth slowed in children, inadequate diet, inadequate exposure to sunlight, severe deficiency leads to rickets, osteomalacia, muscle pain, severe asthma in kids

Deficiency might lead to premature infants

Subdermal hemorrhaging, deficiency leads to uncontrolled bleeding and clotting

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

Vitamin A, retinol 300 μg (1–3 years), 400 μg

Vitamin E, tocopherol 6 mg (1–3 years), 7 mg

Vitamin K, phylloquinone 30 μg (1–3 years), 55 μg

(4–8 years)

(4–8 years)

*Recommended daily intake, Health benefits, and deficiency of liposoluble vitamins [11–13].*

(>4 years)

Vitamin D, cholecalciferol 5 μg (4–8 years) Essential for healthy


*Nanoformulated Delivery Systems of Essential Nutraceuticals and Their Applications DOI: http://dx.doi.org/10.5772/intechopen.86170*

#### **Table 1.**

*Nanoemulsions - Properties, Fabrications and Applications*

hydrophilic vitamins as compared to liposoluble ones [7, 8]. Different approaches have been explored to improve the stability and functionality of hydrophilic vitamins during product development and storage of food because of the exposure to high temperature, oxygen, and light. Novel methods were used by Alishahi et al. [9] to increase the shelf life and delivery of vitamin C using chitosan nanoparticles. In addition, three different vitamins (B9, B12, and C) were successfully encapsulated in water-soluble derivatives of chitosan biopolymer [10]. Their study showed that N,N,N-trimethyl chitosan nanoparticles can successfully be used as a stable vitamin

**Table 1** highlights some of their health benefits and disease prevention [11–13].

The delivery of vitamins using nanotechnology has attracted a number of attention recently [14] and is proposed as one of the possible innovative approaches. Numerous methods including spray-drying, spray-cooling, phase separation, emulsion systems, liposome solid lipid nanoparticles (SLN), and inclusion complexation have been proposed for the nanoformulations of liposoluble vitamins as depicted in **Figure 2**. Some of the methods including nanoemulsions, polymeric and lipid

Many of these vitamins have been found to have major limitations such as low chemical stability, sensitive to oxidation, high melting points, and poor solubility, thus leading to low bioavailability [14]. The inability of the human body to produce vitamins forces humans to have a balanced diet in order to intake the recommended supply of essential nutrients. The inadequate intake of various vitamins through diet may compromise biological functions such as vision, growth and development, immunological activity, reproduction, and cellular growth [11]. The application of adequate treatment can reduce the risk of development of complications related to deficiency of vitamins. Food fortification and supplements have been used as strategies to prevent vitamin deficiency. In order for nutritional supplement premixes and fortified food to work, the vitamins and micronutrients contained in these products need to remain active until consumption, which may not always be the case. Premixes and fortified foods may lose a large percentage of vitamins and micronutrient activity before consumption via processing, packaging, transportation, and storage. Therefore there is an urgent need to develop and explore cost-effective innovative approaches that will improve the stability of nutraceuticals especially liposoluble vitamins.

carrier system with potential applications in foodstuffs.

*Classification of vitamins with some examples of high rich foods.*

nanoparticles, etc. will be discussed in the chapter.

**32**

**Figure 1.**

*Recommended daily intake, Health benefits, and deficiency of liposoluble vitamins [11–13].*

**Figure 2.** *Nanoformulations for liposoluble vitamins [14].*

### **1.1 Nanoemulsions**

Colloidal dispersions consisting of oil droplets dispersed in an aqueous medium in the 5–200 nm range are known as a nanoemulsion. They are isotropic systems, which are kinetically stable compared to conventional emulsions. Furthermore, they are transparent or translucent to the naked eye [15]. They have also been found to hold special characteristics such as protection from oxidant and hydrolysis in oil-in-water

#### **Figure 3.**

*Photographic evidence of the antimicrobial inhibition of (A) garlic essential oil and (B) garlic essential oil nanoemulsions [19].*

(O/W) nanoemulsions [16], encapsulation of hydrophilic drugs [17], enhanced bioavailability of drugs [18], and increased antimicrobial activity of essential oil [19]. **Figure 3** shows an enhanced inhibition level against *Escherichia coli* of garlic essential oil nanoemulsions (GEON) as compared to garlic essential oil [19]. The study by Katata-Seru et al. further revealed an easy and effective Taguchi method for optimizing GEON and as a potential alternative to antimicrobial broiler growth promoters.

There are various types of nanoemulsions and the most common ones are O/W type, water-in-oil (W/O) type, and bi-continuous type, for example, water-in-oilin-water (W/O/W) type. A number of different preparation techniques for nanoemulsions have been investigated intensively using low and high energy. Low energy includes spontaneous emulsification and phase inversion temperature, while highenergy such as microfluidics, high-pressure homogenizers, or ultrasound equipment methods are used. The food-grade nanoemulsions have generated a huge interest using processing operations such as homogenization and mixing and shearing and homogenization [7, 20]. Recently, Öztürk evaluated various studies on enhanced bioavailability of vitamins A, D, and E encapsulated in O/W nanoemulsions and their factors affecting their stability [16]. Emulsion systems for encapsulation of vitamin E showed that nanoemulsion formulation improved the emulsion stability with an average particle size of 277 nm when compared to the standard emulsion [20]. Although it appears that significant research on nanoemulsions is on the rise, Öztürk highlighted a need for more in vivo bioavailability studies of the foods fortified with lipophilic vitamins as their studies are few owing to the higher costs.

#### **1.2 Polymeric nanoparticles**

Polymeric nanoparticles (NPs) are solid carriers capable to adsorb, disperse, entrap, and attach active ingredients to its matrices with the size of smaller than 1 μm. They are produced from preformed polymers by emulsion solvent evaporation, salting out, dialysis, nanoprecipitation, and supercritical fluid (SCF) technology. The NPs have displayed fairly good stability, higher loading efficiency, and controlled release of bioactive compounds as compared to emulsion, micelles, and

**35**

**Figure 4.**

*Nanoformulated Delivery Systems of Essential Nutraceuticals and Their Applications*

liposomes [14]. In addition, they have been studied extensively in the nutraceutical field because of characteristics including increased stability, the capability to protect

Studies have fabricated a unique polymeric vitamin E-modified aliphatic polycarbonate (mPEG-PCC-VE) to assist oral absorption of oleanolic acid (OA) [23]. The OA demonstrated excellent pharmacological activities in the clinical treatment of hypoglycemia, immune regulation, acute jaundice, and chronic toxic hepatitis. In spite of this, OA has limited water solubility and poor intestinal mucosa permeability when delivered orally. The results of OA encapsulated mPEG-PCC-VE NPs illustrated homogeneous 170 nm particle size with a drug loading of 8.9% and a

Lipid nanoparticles were developed as an alternative to traditional nanosystems such as polymeric particles and liposomes. Lipid nanoparticles can be defined as colloidal particles composed of lipids stabilized by surfactants that are

Lipid particles can be produced using various methods such as high-pressure homogenization, microemulsion, emulsion solvent evaporation, emulsificationsolvent diffusion, solvent displacement, phase inversion, ultrasonication, and membrane contractor technique [24]. However, of these techniques, only a few have been applied to prepare lipid nanoparticles with vitamins. Vitamins are sensitive

*Models for the structure solid lipid nanoparticles and nanostructured lipid carriers that can be obtained under* 

*different conditions determined by the nature of the components and their relative solubility [25].*

solid at ambient temperature with sizes varying between 40 and 1000 nm [24, 25]. The first lipid nanoparticle to be produced was solid lipid nanoparticles as depicted in **Figure 4**. SLN is made from solid lipid only. The second generation of lipid nanoparticles was developed a few years later called nanostructured lipid nanoparticles (NLC). NLC is made from a blend of solid and liquid (oil) lipids [26]. The addition of oil in NLC formulation is meant to distort the formation of perfectly structured lipid crystals found in SLN, thus creating more room with uptake capacity for the encapsulated active. This was first shown by Jenning and Gohla, when they increased the loading capacity of retinol (vitamin A) from 1 to

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

potential platform to facilitate the oral delivery of OA.

drugs, etc. [21, 22].

**1.3 Lipid nanoparticles**

5% by using NLC [27].

*Nanoformulated Delivery Systems of Essential Nutraceuticals and Their Applications DOI: http://dx.doi.org/10.5772/intechopen.86170*

liposomes [14]. In addition, they have been studied extensively in the nutraceutical field because of characteristics including increased stability, the capability to protect drugs, etc. [21, 22].

Studies have fabricated a unique polymeric vitamin E-modified aliphatic polycarbonate (mPEG-PCC-VE) to assist oral absorption of oleanolic acid (OA) [23]. The OA demonstrated excellent pharmacological activities in the clinical treatment of hypoglycemia, immune regulation, acute jaundice, and chronic toxic hepatitis. In spite of this, OA has limited water solubility and poor intestinal mucosa permeability when delivered orally. The results of OA encapsulated mPEG-PCC-VE NPs illustrated homogeneous 170 nm particle size with a drug loading of 8.9% and a potential platform to facilitate the oral delivery of OA.
