*2.1.2 Ionic gelation*

This method is based on the electrostatic interaction of the two aqueous phases and the nanospheres are prepared from natural polymers. Polyelectrolytes form hydrogel beads by cross-linking with counterions. These hydrogel beads are also called gelispheres. Gelispheres spreads into the polymer structure and forms a cross-linked cage. In this way, biomolecules can be trapped in this lattice structure. Examples of synthetic monomers and polymers used in this method include hydroxyethyl methacrylate, N-vinyl-2-pyrrolidone, N-isopropylacrylamide, vinyl acetate, acrylic acid, polyethylene glycol acrylate/methacrylate, polyethylene glycol diacrylate/dimethacrylate. Chitosan, gelatin, alginate fibrin, collagen, hyaluronic acid, dextran can be used as a natural polymer. Multivalent cations are generally

magnesium, sodium, calcium, potassium, ferric, aluminum, barium and zinc ions. In the experimental stage, polymer and electrolyte concentrations, pH, temperature and biomolecule concentrations are important parameters to be considered.

by this method have more ability to convert poorly soluble and poorly absorbed

*The Components of Functional Nanosystems and Nanostructures*

to the literature. **Figure 4** schematizes the synthesized gold nanospheres.

barriers, cosmetics and many other areas [1].

**2.2 Quantum dots**

Enhanced lithium storage

Hydrogen production and photocatalytic activity

For sensing trace cysteine in

For application in water

For high-performance supercapacitors

*Some examples of nanospheres, according to the literature.*

Water treatment and improved lubricating performance

properties

HeLa cells

treatment

**Table 1.**

**117**

Nanospheres are used effectively in controlled drug delivery systems, tumortargeted treatment methods, tumor-targeted treatment methods, epithelial cell therapy, genetic engineering studies, treatment methods targeting blood–brain

Quantum mechanics is the starting point of nanotechnology. These nano-sized semiconductor crystals are called quantum dots. Quantum dots are giant atomic structures that contain thousands of atoms. When substances are nano-sized, they

**Purpose of usage Nanospheres References**

For lithium-ion batteries Pyrite/carbon nanospheres [12]

For PSA detection Polydopamine nanospheres loaded with L-cysteine-

coated cadmium sulfide quantum dots

Ultra-small ZnFe2O4 nanosphere [10]

High specific surface area TiO2 nanosphere [11]

Gold-silver nanospheres [13]

Alkyl-capped copper oxide nanospheres [14]

MoO3 nanospheres [16]

CuS nanospheres [17]

[15]

Particularly particle size and surface distribution properties are essential characteristic analyzes for the characterization of nanospheres. Because particle sizes and surface distributions also illuminate the properties of in vivo distribution, biological fate, toxicity and targeting ability. For the characterization of these properties, scanning electron microscopy (SEM), transmission electron microscopy (TEM), photon correlation spectroscopy methods are used. The Zeta potential analysis provides insightful information about load stability and particle collection. Zetasizer is used for this analysis. Fourier transform infrared spectroscopy (FTIR) analyses are performed to reveal the chemical bonding between the active substance and the polymers. The physical state of the active substance in the nanospheres is determined by differential scanning calorimetry (DSC) analysis after the lyophilization of the nanospheres. It can be applied many analysis methods such as in vitro drug release studies, drug release kinetics and stability study. Stability studies help to examine the effects of nanospheres on the physicochemical parameters of their formulations. In this way, suitable storage conditions are determined. Absorption and storage at room temperatures are performed for approximately 6 months and the observed changes in physicochemical parameters are recorded. Appropriate storage conditions are determined according to the results obtained. **Table 1** shows the intended use of the nanospheres synthesized according

drugs into better deliverables.

*DOI: http://dx.doi.org/10.5772/intechopen.92027*

### *2.1.3 Salting out*

This method is based on a salt interaction such as a polymer, organic solvent, and magnesium chloride hexahydrate or magnesium acetate tetrahydrate. An emulsification mechanism is performed. Salting out method is based on increasing hydrophobic effect as a result of electronic repulsion of dissolved anions with highdensity loads. This resulting hydrophobic effect increases the uniformity of the water-soluble intermediate phase structure, reduces entropy and causes agglomeration of the solvent. This is because the presence of high-charge salts in the system decreases entropy by increasing the regularity between similar surfaces, this result is also desirable. Anions reducing water solubility; OH ≈ SO4 <sup>2</sup> ≈ CO3 <sup>2</sup> > ClO3 ≈ Cl ≈ OAc ≈ IO3 > Br ≈ I > NO3 and the cations: Na<sup>+</sup> > K<sup>+</sup> > Li<sup>+</sup> ≈ Ba2+ ≈ Rb+ ≈ Ca2+ ≈ Co2+ ≈ Mg2+ ≈ Fe2+ ≈ Zn2+ ≈ Cs+ ≈ Mn2+ ≈ Al3+ > NH4<sup>+</sup> > H<sup>+</sup> .

#### *2.1.4 Controlled gelification*

In this method, gelation is formed using calcium chloride and sodium alginate. A suitable mixture of these two compounds results in gelling. Poly-L-lysine is added to the resulting solution as a polymer and a polyelectrolyte mixture is formed by mixing. Subsequently, nanospheres are synthesized by centrifugation [8].

#### *2.1.5 Solvent evaporation*

This method is based on the principle of emulsifying the active substance in the polymer and an organic solvent and removing the solvent by reducing the temperature and pressure. In this method, polyvinylchloride or gelatin may be used as the emulsifying agent.

#### *2.1.6 Solvent displacement*

It is one of the most widely used methods for the synthesis of nanoparticles. The solvent displacement is based on the displacement of a semi-polar solvent with the polymer interface. In this method, the organic phase containing the active substance and the polymer structure in the aqueous phase is self-emulsified. The polymer and active ingredient are dissolved in an organic solvent such as watermiscible ethanol, methanol or acetone. The organic phase is injected into the aqueous phase containing the active ingredient. The nanospheres are synthesized by precipitating the polymer in which the organic phase is dispersed in the aqueous phase.

#### *2.1.7 Desolvation technique*

This method is particularly preferred for obtaining nanospheres from natural polymers. The active substance is added to the polymer and solvent, and crosslinking is performed. Crosslinking agents must be added to effect crosslinking. The suspension is lyophilized by centrifugation, and the nanospheres are synthesized [9].

The most common and advantageous method used in the synthesis of nanospheres is the solvent displacement method. This method will provide great advantages especially in controlled drug release systems. Nanospheres synthesized
