Introduction

Food or food components that provide health benefits beyond basic nutrition, such as preventing or treating diseases, are called nutraceuticals [1]. Consumer interest in nutraceuticals has grown due to their well-known health benefits and increasing demand for healthy and organic foods. This has led to a boost in the global nutraceuticals market. [2]. The steadily growing demand for dietary supplements and functional foods is a key driver of the global nutraceutical market. A Grand View Research report projects that the market will grow at a compound annual growth rate (CAGR) of 8-9% from 2020 to 2028. [3]. The COVID-19 pandemic has raised awareness of the importance of nutraceuticals, such as immune boosters, vitamins, antioxidants, and minerals. These products have been shown to be effective in meeting overall nutritional requirements. However, most nutraceuticals are unstable in light and air, which is a major hurdle to their widespread use. [4]. Different approaches are utilized to counter this hurdle, and this includes (i) the development and design new food matrices [5] and (ii) the use of encapsulation technologies [6]. Another problem with nutraceuticals is their solubility and pharmacokinetic properties, such as bioavailability, durability, and absorption. This review describes the use of different nanotechnology methods to overcome these issues [7,8]. (Figure 1).

Figure 1: Shows the advantages of nanocarriers over bioactive challenges to improve the bioavailability of actives.

Nanoparticle-based delivery systems are promising encapsulation technologies for the industrial application of nutraceutical bioactives. Two types of nanoparticle-based systems are used: liquid and solid-delivery systems. Solid nanodelivery systems consist of three types of encapsulation: nanocrystals, lipid nanoparticles, and polymeric nanoparticles. Liquid nanodelivery systems consist of nanovesicles, nanoemulsions, and gas bubbles (foams, aerosols), which are dispersed in a continuous aqueous medium. These systems are discussed briefly in the following sections.

Dr. Norio Taniguchi introduced the term nanotechnology, which consists of generating and utilizing materials, mechanisms, or systems at a nanometer scale [9]. The U.S. National Nanotechnology Initiative describes nanoparticles (NPs) in the particle size of 1-100 nm [10-12]. The novel properties of nanomaterials offer many new opportunities for food processing, safety, and packaging [13]. Nanocarriers offer several advantages, including improved solubility, protection against oxidation, preservation of volatile bioactives, and protection of the encapsulated elements from environmental parameters such as oxygen, heat, water, and light. Additionally, nanocarriers can mask taste, improve stability, and extend shelf life [14]. Figure 2 describe the different nanoparticle based delivery systems or technologies used in nutraceutical product development. In recent years, several nanoparticle-based delivery systems, such as nanosponges, dendrimers, nanosuspensions, nanoemulsions, liposomes, nanohydrogels, and carbon nanotubes, have been extensively evaluated for their ability to improve the bioavailability and other quality attributes of nutraceutical bioactives. These nanoformulations can provide targeted delivery of the phytochemical and sustained release, in addition to improving bioavailability and therapeutic efficacy.

Figure 2: Schematic diagram of different Nanoparticle based delivery systems or technologies.

Nanocarriers are nanosized materials with a diameter of 1-100 nm that can carry multiple drugs and/or imaging agents. They play an important role in determining both in vitro and in vivo performance of bioactives, each with its own attributes. The selection of a specific nanocarrier depends on several parameters, such as the type of bioactives, their solubility, bioavailability, and target site. Nanocarrier systems consist of cores that can be liquid (emulsions and microemulsions), solid (solid lipid nanoparticles, or SLNs), or a mixture of solid and liquid domains (nanostructured lipid carriers, or NLCs). Particles for the encapsulation of hydrophilic bioactives are composed of an aqueous core surrounded by a shell that is distinct from the surrounding continuous phase. These include nanohydrogels, liposomes, and colloidosomes [15,16].

Poorly soluble bioactives are a challenging problem for formulators in the nutraceutical industry. Conventional approaches to solubility enhancement are limited in their applicability, especially when the bioactives are poorly soluble in both aqueous and non-aqueous media. Nanotechnology is a broad range of technologies, materials, and manufacturing processes that can be used to design and/or enhance many products, including medicinal products. This technology has achieved significant progress. Novel nanoformulations, such as nanoemulsions, nanosuspensions, liposomes, polymeric micelles, dendrimers, and gold nanoparticles, have been shown to enhance the delivery of bioactives and ultimately their bioavailability [17-20].

Nanocarriers

Micro and Nanoemulsions

An emulsion is a colloidal dispersion of two immiscible liquids, one of which is dispersed as tiny spherical droplets in the other. Emulsions are classified based on the relative spatial distribution of the oil and aqueous phases. Oil-in-water (O/W) emulsions are those in which oil droplets are dispersed in an aqueous phase. These emulsions can be used for the delivery of hydrophobic active substances. Water-in-oil (W/O) emulsions are those in which water droplets are dispersed in an oil phase. These emulsions are used for the delivery of hydrophilic compounds. [21-24]. Further, in the last few years, multiple emulsions have been investigated due to their importance in scientific applications. A Multiple emulsion is one in which the dispersed droplets contain even finer droplets of a different phase. Two types of multiple emulsions may exist including an oil-in-water-in-oil (O/W/O) emulsion and a water-in-oil-in-water (W/O/W) emulsion [25]. Emulsions can be classified into microemulsions and nanoemulsions based on their droplet size ranges. Microemulsions have droplet sizes in the range of 0.1-5 mm, while nanoemulsions have droplet sizes in the range of 20-100 nm and 5-50 nm. The ideal particle size for an emulsion depends on the methods of preparation, the type of emulsifier used, the target molecule, and the industrial application. [26]. Nanoemulsions have been extensively explored as drug delivery systems.

Over the past decade, nanoemulsions have gained popularity in food, beverage, and cosmetic products due to their potential advantages over conventional emulsions, which are associated with their smaller droplet size [27]. Nanoemulsions can be fabricated using a variety of techniques, which can be categorized as either low-energy or high-energy emulsification techniques. Low-energy techniques rely on spontaneous emulsification, which occurs when the surface tension of a mixture of oil, water, and surfactant is reduced by modifying the solution or physicochemical conditions. This results in the formation of tiny oil droplets. [28-30].

In the food industry, high-energy techniques are the most popular method for creating nanoemulsions. High-energy techniques are based on mechanical devices, which makes them easy to scale up and produce a high throughput. [27]. High-pressure homogenization is the most appropriate high-energy technique for creating nanoemulsions in the food industry. This technique involves forming an emulsion premix by mixing the oil, water, and emulsifier together using a high-shear mixer. The smaller size particles are then created by passing the mixture through a small orifice under high pressure. This generates intense forces that break large oil droplets into smaller droplets [31-34].

Microfluidization and ultrasonication are other high-energy techniques that can be used to create nanoemulsions. Microfluidizers use high pressure to convert larger emulsion droplets into smaller ones. The process involves passing a coarse emulsion through two separate channels under high pressure. The two channels meet at the end of the device, where the generated forces lead to the formation of smaller droplets. The final droplet size depends on the number of passes and the pressure applied. Jafari, et al. investigated the efficiency of microfluidization and ultrasound as emulsification techniques that produced nanoemulsions in sizes ranging from 150 to 700nm. Emulsions produced with Microfluidization provided a narrower droplet size distribution and sonication was more convenient in terms of operation and cleaning [35].

In ultrasonication, high-intensity ultrasonic waves create cavitation bubbles in the liquid. These bubbles oscillate rapidly and eventually implode, generating intense disruptive forces that break up the oil droplets into smaller emulsion droplets. [36]. Different Nanoemulsion technologies were used to improve the bioavailability of nutraceutical activities entitled in Table 1.