A Review on Nanoparticles: Preparation and Characterization of Nanoparticles

 

Saloni Manglik, Jaya Singh*

Innovative College of Pharmacy, Greater Noida, Uttar Pradesh – 201308.

 

ABSTRACT:

The development of innovative medication delivery systems has increased at an exponential rate in the last few years. Nanoparticles are particles with a size of between one and one hundred nanometers. Nanoparticles provide substantial benefits over conventional drug administration in terms of high bioavailability, high stability, high drug-carrying capacity, and other characteristics. This review concentrated mostly on the classification of nanoparticles, the technique of synthesis, the evaluation of nanoparticles, and the list of FDA-approved nanomedicines now available on the market.

 

 

 

INTRODUCTION:

Nanotechnology is a fascinating field for developing medication delivery systems based on nanoparticles with dimensions ranging from 1 to 100 nanometers. Nanoparticles have the potential to deliver a wide variety of compounds to different parts of the body for long periods.

 

Materials with overall dimensions in the nanoscale, or less than 100 nanometers, are referred to as nanoparticles. These materials have emerged as key players in modern medicine in recent years, with applications ranging from contrast agents in medical imaging to gene carriers for individual cell delivery[1]. The term nanomaterial is described as “a manufactured or natural material that possesses unbound, aggregated or agglomerated particles where external dimensions are between 1–100 nm size range”, according to the EU Commission. The British Standards Institution proposed the following definitions for the scientific terms that have been used in table 1.

 

Table 1: Shows the relationship between nanoscience and nanotechnology.

Nanocale	Approximately 1 to 1000 nm size range.
Nanoscience	The science and study of matter at the nanoscale that deals with understanding their size and structure-dependent properties and compares the emergence of individual atoms or molecules or bulk material-related differences.
Nano technology	Manipulation and control of matter on the nanoscale dimension by using scientific knowledge of various industrial and biomedical applications.
Nano material	Material with any internal or external structures on the nanoscale dimension.
Nano-object	Material that possesses one or more peripheral nanoscale dimensions.
Nano particle	Nano-object with three external nanoscale dimensions. The terms nanorod or nanoplate are employed, instead of nanoparticle (NP) when the longest and the shortest axes lengths of a nano-object are different.
Nanofiber	When two similar exterior nanoscale dimensions and a third larger dimension are present in a nanomaterial, it is referred to as nanofiber.
Nano composite	Multiphase structure with at least one phase on the nanoscale dimension.
Nano structure	Composition of interconnected constituent parts in the nanoscale region.
Nanostructured material	Materials containing internal or surface nanostructure.

 

Table 2 Classification of Nanoparticles:

 

ADVANTAGES OF NANOPARTICLES:

1.     Nanoparticles have high Stability.

2.     Nanoparticles have high carrier capacity.

3.     Nanoparticles increase resistance time in the body.

4.     Nanoparticles target drugs to specific locations in the body which results in the protection of non-target tissues and cells from severe side effects.

5.     Nanoparticles also provide controlled and target drug delivery.

6.     Nanoparticles can be used for parental, oral as well as topical routes.

 

TYPES OF NANOPARTICLES:

1.    Nanosphere (Nanospheres or matrix-type nanodevices are polymeric NPs where the entire mass is solid and consists of spherical polymeric matrices)

2.    Nano-capsule (Nano-capsule or reservoir-type nanodevices are vesicular systems that consist of a liquid core (water or oil) in which a drug can be loaded surrounded by a polymeric membrane or coating) [2].

 

CLASSIFICATION OF NANOPARTICLES:

1. ORGANIC-BASED NANOPARTICLES:

Organic nanoparticles or polymers are generally known as dendrimers, micelles, liposomes, and ferritin, among others. Some nanoparticles, such as micelles and liposomes, have a hollow core, sometimes known as nano-capsules, and are sensitive to thermal and electromagnetic radiation such as heat and light. Because of their distinct properties, they are an excellent alternative for drug delivery. Apart from their usual properties like size, composition, surface shape, etc., their drug-carrying capacity, stability, and delivery systems, whether an entrapped drug or adsorbed drug system, define their area of applications and efficiency. Organic nanoparticles are frequently used in biomedical fields, such as medication delivery systems since they are efficient and can be injected into specific regions of the body, a process known as targeted drug delivery [3].

 

A.   DENDRIMERS:

Dendrimers are a new type of polymer with a controlled structure and nanometric dimensions. Dendrimers, which are utilized in drug administration and imaging, are typically 10 to 100 nm in diameter and have numerous functional groups on their surface, making them suitable drug carriers. Dendrimers are widely used in the medical and biological industries because they have diverse reactive surface groups (nanostructure) and are compatible with organic structures such as DNA. Nonsteroidal anti-inflammatory formulations, anti bacterial and antiviral medications, anticancer agents, pro-drugs, and screening agents for high-throughput drug discovery are among the pharmaceutical applications of dendrimers [4].

 

Fig 1- Shows the activity of dendrimer

 

B.    LIPOSOMES:

Liposomes are microscopic vesicles with a spherical form made up of one or more phospholipid bilayer membranes. The inner core of liposomes is made up of hydrophilic phospholipids into which hydrophilic molecules can be inserted. Lipophilic compounds, on the other hand, tend to stay in the lipid section of the phospholipid bilayer. Oral drug delivery methods, as well as the oral delivery of therapeutic proteins and peptides, have been studied, primarily for the oral delivery of the insulin hormone. The benefits of liposomes in the oral distribution of insulin hormone include protection from enzymatic hydrolysis by enzymes found in the gastrointestinal tract (GIT) and improved insulin hormone absorption in the small intestine [5].

 

Fig 2. Activity of liposome

 

C.   MICELLES:

Micelles are amphiphilic structures with a hydrophobic core and a hydrophilic shell that are spherical. The hydrophilic coating renders the micelle water-soluble, allowing for intravenous delivery, while the hydrophobic center transports a therapeutic payload. The hydrophilic shell of polymeric micelles and their nanoscale dimensions (less than 50 nm) protect them from being eliminated by the reticular-endothelial system, enhancing their circulation time and ability to transport the medicine to the target [6].

 

Fig3. Representation of  Micelles

 

2)    INORGANIC-BASED NANOPARTICLES:

These are those particles that are not made up of carbon. They are generally categorized into metal-based and metal-oxide-based nanoparticles.

 

a)    METAL-BASED:

Metal-based nanoparticles are nanoparticles that are manufactured from metals to nanometric sizes using destructive or constructive processes. Almost every metal may be manufactured into nanoparticle form. Aluminum (Al), cadmium (Cd), cobalt (Co), copper (Cu), gold (Au), iron (Fe), lead (Pb), silver (Ag), and zinc are the most widely employed metals for nanoparticle synthesis (Zn). Nanoparticles have unique characteristics such as sizes ranging from 10 to 100nm, surface characteristics such as a high surface area to volume ratio, pore size, surface charge, and surface charge density, crystalline, and amorphous structures, spherical and cylindrical shapes, and color, reactivity, and sensitivity to environmental factors such as air, moisture, heat, and sunlight, etc [3].

 

b)    METAL-OXIDE BASED:

Due to their higher stability than metal nanoparticles, metal oxide nanoparticles are the next most popular nanomedicines used as therapeutic and diagnostic agents for cardiovascular disorders. Metal oxide-based nanoparticles are synthesized to alter the properties of their respective metal-based nanoparticles. For example, iron (Fe) nanoparticles instantly oxidize to iron oxide (Fe2O3) in the presence of oxygen at room temperature, increasing their reactivity compared to iron nanoparticles. Because of their improved reactivity and efficiency, metal oxide nanoparticles are commonly produced. Aluminum oxide (Al2O3), Cerium oxide (CeO2), Iron oxide (Fe2O3), Magnetite (Fe3O4), Silicon dioxide (SiO2), Titanium oxide (TiO2), and Zinc oxide (ZnO) are the most typically manufactured (ZnO) [3][5].

 

c)      SEMICONDUCTOR:

Semiconductor materials have qualities that are intermediate between metals and nonmetals, and as a result, they have a wide range of applications in the literature. Because semiconductor NPs have large band gaps, bandgap tuning caused considerable changes in their characteristics. As a result, they play a crucial role in photocatalysis, photo optics, and electronic devices. Due to their optimal bandgap and band edge placements, several semiconductor NPs are found to be particularly efficient in water splitting applications [7].

 

d)    CERAMICS:

Inorganic solids such as oxides, carbides, carbonates, and phosphates make up ceramic nanoparticles. These nanoparticles are chemically inert and have high thermal resistance.

 

They can be used for photocatalysis, dye photodegradation, medication administration, and imaging [8].

Ceramic nanoparticles can be used as a good drug delivery agent by manipulating several of their properties, such as size, surface area, porosity, the surface to volume ratio, and so on. These nanoparticles have proven to be an efficient medication delivery mechanism for a variety of disorders, including bacterial infections, glaucoma, and cancer.

 

3)     CARBON-BASED NANOPARTICLES:

The nanoparticles made completely of carbon are known as carbon-based. They can be classified into fullerenes, graphene, carbon nanotubes (CNT), carbon nanofibers and carbon black, and sometimes activated carbon in nanosize.

 

a)    CARBON NANOTUBES:

CNTs are tubular, elongated structures with a diameter of 1–2 nm. Based on their diameter telicity, they can be classified as metallic or semiconducting. These resemble a graphite sheet rolling on itself in terms of structure. Because the rolled sheets can have one, two, or multiple walls, they are referred to as single-walled (SWNTs), double-walled (DWNTs), or multi-walled carbon nanotubes (MWNTs) respectively. They're commonly made by depositing carbon precursors, particularly atomic carbons, evaporated from graphite using a laser or an electric arc onto metal particles. They have recently been produced using the chemical vapor deposition (CVD) method. These materials are employed in nanocomposites for several commercial purposes, such as fillers, effective gas adsorbents for environmental remediation, and as a support medium for various inorganic and organic catalysts, due to their unique physical, chemical, and mechanical features[7].

 

Fig 4- Rolling of graphite layer into single-walled and multiple-walled CNTs

 

b)    FULLERENES:

Fullerenes (C60) is a carbon molecule that is spherical and made up of carbon atoms held together by sp2 hybridization. About 28 to 1500 carbon atoms from the spherical structure with diameters up to 8.2 nm for a single layer and 4 to 36 nm for multi-layered fullerenes. Nanomaterials composed of globular hollow cages, such as allotropic forms of carbon, are found in fullerenes. Because of their electrical conductivity, high strength, structure, electron affinity, and adaptability, they have piqued commercial interest. The carbon units in these materials are organized pentagonal and hexagonal, and each carbon is sp2 hybridized. Since fullerenes are empty structures with dimensions similar to several biologically active molecules, they can be filled with different substances and find potential medical applications [7].

 

Fig 5. Activity of Fullerenes

 

Nanomedicines approved by FDA:

Table 3 -Nanomedicines that are approved by FDA [9]

 

Fig. 6-Review of the method of preparation

 

METHOD OF PREPARATION:

1.     SOLVENT EVAPORATION METHOD:

The polymer (chitosan) is dissolved in volatile organic solvent (Ethyl acetate) into which the drug (metformin hydrochloride) is dissolved.

 

 

The organic solution is then added to the aqueous phase which contains a surfactant (Polyvinyl alcohol) under high homogenization to form an emulsion.

 

 

After the formation of stable emulsion, the organic solvent is evaporated from the polymer solution either by increasing the temperature under reduced pressure or by continuous stirring.

 

 

The nanoparticles are collected by ultracentrifugation and washed with distilled water several times to remove stabilizer residue or any free drug and lyophilized for storage.

 

2.     DOUBLE-EMULSION AND PREPARATION METHOD:

The emulsion and evaporation methods are limited in their ability to encapsulate hydrophilic drugs. As a result, the double emulsion technique is used to encapsulate hydrophilic drugs, which involves adding aqueous drug solutions to organic polymer solutions while vigorously stirring to form w/o emulsions. This w/o emulsion is continuously stirred into the second aqueous phase to generate the w/o/w emulsion. The emulsion is then evaporated to remove the solvent, and nanoparticles can be separated using high-speed centrifugation. The formed nanoparticles must be thoroughly washed before lyophilization. In this method the amount of hydrophilic drug to be incorporated, the concentration of stabilizer used, the polymer concentration, the volume of the aqueous phase are the variables that affect the characterization of nanoparticles[4].

 

3.     EMULSION-DIFFUSION METHOD:

This is yet another popular approach for making nanoparticles. To ensure the initial thermodynamic equilibrium of both liquids, the encapsulating polymer is dissolved in a partly water-miscible solvent (such as propylene carbonate or benzyl alcohol) and saturated with water. The polymer-water saturated solvent phase is then emulsified in an aqueous solution containing a stabilizer, resulting in solvent diffusion into the exterior phase and the creation of nanospheres or nano-capsules, depending on the oil-to-polymer ratio. Finally, depending on the boiling point of the solvent, it is removed by evaporation or filtration. High encapsulation efficiency (usually 70%), no requirement for homogenization, high batch-to-batch reproducibility, ease of scaleup, simplicity, and limited size distribution are just a few of the benefits of this approach [4].

 

4.     SALTING OUT METHOD:

The separation of a water-miscible solvent from an aqueous solution is based on the salting-out action. The polymer and medicine are first dissolved in a solvent, then emulsified into an aqueous gel comprising a salting-out agent (electrolytes like magnesium chloride and calcium chloride, or non-electrolytes like sucrose) and a colloidal stabilizer like polyvinylpyrrolidone or hydroxyethyl cellulose. This oil/water emulsion is diluted with enough water or aqueous solution to increase solvent penetration into the aqueous phase, resulting in the formation of nanospheres. Stirring rate, internal/external phase ratio, polymer concentration in the organic phase, type of electrolyte concentration, and type of stabilizer in the aqueous phase are all variables that can be changed during the manufacturing process. Because salting-out does not require a temperature rise, it may be advantageous when processing heat-sensitive compounds.

 

5.     SOLVENT DISPLACEMENT / PRECIPITATION METHOD:

Polymers, drugs, and/or lipophilic surfactants are dissolved in acetone or ethanol, a semipolar water-miscible solvent. Under magnetic stirring, the solution is poured or injected into an aqueous solution containing a stabilizer. Rapid solvent diffusion results in the formation of nanoparticles in an instant.

Under reduced pressure, the solvent is then extracted from the suspensions. The size of the particles is affected by the rate at which the organic phase is added to the aqueous phase. As the rate of mixing of the two phases rises, it was discovered that both particle size and drug entrapment decrease. Most poorly soluble medicines are well suited to the nanoprecipitation technique [4].

 

COMMONLY USED MATERIAL FOR PREPARATION OF  NANOPARTICLES:

Table 4-Activity of polymers with solvent

 

 

 

 

 

EVALUATION PARAMETERS OF NANOPARTICLES:

1.     PERCENTAGE YIELD:

It can be calcuated by comparing the total weight of the nanoparticle generated to the weight of the copolymer and drug combined.

 

2.     DRUG ENTRAPMENT EFFICIENCY:

 

3.     PARTICLE SIZE ANALYSIS:

Particle size and distribution are significant properties of nanoparticles because they influence the distribution, pharmacological action, toxicity, and site targeting.

It can be done by-

a)    Photon-correlation spectroscopy / Dynamic light scattering

b)   Scanning electron microscopy

 

4.     SCANNING ELECTRON MICROSCOPE:

SEM is a technique for determining particle size, shape, and texture using only milligram amounts of material. For SEM characterization, nanoparticles solution should be first converted into a dry powder, which is then mounted on a sample holder followed by coating with a conductive metal, such as gold, using a sputter coater. The sample is then scanned with a focused fine beam of electrons. The surface characteristics of the sample are obtained from the secondary electrons emitted from the sample surface. The nanoparticles must be able to withstand vacuum, and the electron beam can damage the polymer. The mean size obtained by SEM is comparable with results obtained by dynamic light scattering. Moreover, these techniques are time-consuming, costly, and frequently need complementary information about sizing distribution.

 

5.     ZETA POTENTIAL:

The difference in potential between the main fluid in which a particle is disseminated and the layer of fluid containing oppositely charged ions that are associated with the nanoparticle surface is measured by the Zeta Potential. Positively charged particles will bond to negatively charged surfaces, and vice versa. Zeta-potential (also known as the electrokinetic potential) is a measure of the “effective” electric charge on the nanoparticle surface and quantifies the charge stability of colloidal nanoparticles. When a nanoparticle has a net surface charge, the charge is “screened” by an increased concentration of ions of opposite charge near the nanoparticle surface. This layer of oppositely charged ions moves with the nanoparticle, and together the layer of surface charge and oppositely charged ions are referred to as the electrical double layer. The magnitude of zeta potential helps us to provide information about particle stability [10].

 

6.     IN-VITRO RELEASE STUDY:

It was done in a USP Type II (paddle type) dissolving equipment with a 50rpm-100rpm rotating speed. The produced nanoparticle suspension was immersed in 900ml of phosphate buffer solution in a vessel at 37 土 0.20℃. A certain amount of medium (5ml) was removed at a specific time interval, and the same volume of dissolution medium was replenished in the flask to maintain a constant volume. A UV spectrophotometer was used to examine the withdrawn sample [11].

 

7.     KINETIC STUDY:

For estimation of kinetic and mechanism of drug release, the result of in-vitro drug release study of nanoparticle was fitted with the various kinetic equation, like-

a). Zero-order (cumulative % release vs. time) b). The first order (log % drug remaining vs. time)

c). Higuchi’s model (cumulative % drug release vs. square root of time)

 

CONCLUSION:

Nanotechnology is strengthening the performance and efficiency of ordinary objects, which is helping us live better lives every day. Nanotechnology has established itself as a cutting-edge branch of study in which substantial research is being conducted to put the technology into practice. It is currently being tested for a variety of novel applications to improve the efficiency and performance of an object or process while simultaneously lowering the cost of the product or process to make it more affordable for everyone. Because of its efficiency and ability to be environmentally benign, nanotechnology has a promising future ahead of it. Recently, there has been an upsurge in the use and potential of nanoparticles, particularly in certain industries. Intensive research and development have been conducted in recent years in drug delivery, cancer treatment, diabetes treatment, and other fields. It appears that there will be a significant increase in the amount of time spent

conducting nanoparticle research.

 

REFERENCE:

1.      Shashi K Murthy, Nanoparticle in Modern Medicine, 2019, V.2(2), 129-141

2.      Takashi Tatsumi, Studies in Surface Science and catalysis, 2018,179, 7-524

3.      Anu Mary Elias, Review on Classification and characterization of Nanoparticles, 2017, V.263, 3-9

4.      Sovan Lal Pal, Nanoparticle: An Overview of Preparation and Characterization, 2016, V.1(06), 228-234

5.      Dawin Khiev, Emerging Nano-formulation and Nanomedicines application foe Ocular Drug delivery, 2021, V.11, 173

6.      Zoraida P. Aguilar, Nanomaterial for Medical Applications, 2017, 33-82

7.      Ibrahim Khan, Nanoparticles: Properties, application, and toxicities, 2019, V.12, 908-931

8.      Sindu C. Thomas, Ceramic Nanoparticle, 2015, V.21(42), 88-6165

9.      Jayanta Kumar Patra, Nano based Drug delivery system: Recent development and prospect, 2018, V.16, 2-15

10.   Sanjukta Durah, Formulation, and Evaluation of Metformin Engineered Polymeric Nanoparticles, 2015, V.6(3), 1006-1017

11.   Vipin Kumar Kamboj, Preparation and Characterization of Metformin Loaded Stearic acid  Coupled F127 Nanoparticles, 2018, V.11, 212-217

 

 

Received on 07.09.2021            Accepted on 22.09.2021           

Accepted on 01.10.2021              ©A&V Publications all right reserved