INTRODUCTION:

Science and engineering at the nanoscale are combined to form nanotechnology. Richard Feynman, a physicist, introduced this technology. This method first appeared at the beginning of the 20^th century. The term "nanotechnology" refers to the newly developing field of creating materials, devices, and systems at the nanoscale, or between one and one hundred nanometers. High surface volume ratios are found in nano formulations.

The field of nanotechnology involves the fabrication of small devices, catalysts, sensors, and other items. Nanomaterial’s research has emerged as one of the most significant and fascinating areas of study in the fields of physics, chemistry, biology, medicine, engineering, and technology in recent years. The design, development, and application of materials at the atomic, molecular, and macromolecular range are represented by nanotechnology¹_.

Particles that fall within the size range of 1 to 100nm are referred to as nanoparticles. Because both atoms and molecules function differently at this size, the formulations have unique uses that set them apart from others. invisible to the naked eye. The process of creating nanoparticles involves the use of biocompatible and biodegradable polymers. These polymers have the ability to alter the drug's actual activity by increasing adhesiveness, delaying the drug's release, or both. Because of their smaller size, nanoparticles are different from bulk material. An increase in the surface area per mass of the material allows for a greater amount of it to come into contact with the surroundings. Sub-nanoscale colloidal drug delivery vehicles are called nanoparticles. Larger particles of the same substance have different properties than nanoparticles. Pharmaceutical nanoparticles are drug carriers that are smaller than a micron and can either be biodegradable or not²_.

In order to increase drug bioavailability, pharmaceutical companies are currently confronted with the challenge of improving the dissolution characteristic of poorly watersoluble drugs. For example, they have beneficial controlled release properties and aid in boosting the stability of medications and proteins. The synthesis of various nanoparticle types using chemical, physical, and biological methods was the main focus of this review. But biological methods are easy, safe, quick, and environmentally friendly; chemical and physical methods, on the other hand, are costly and dangerous. Additionally, it describes the properties of nanoparticles and concludes with a number of uses.

Pathogenesis of ALD

To date, our understanding of the precise pathogenesis of ALD is still very limited.^3,4As a direct hepatotoxin, alcohol consumption initiates a number of metabolic reactions that impact the ultimate hepatotoxic response⁵_. The current theory holds that alcohol metabolised by the hepatocyte starts a pathogenic process that includes the production of protein-aldehyde adducts, immunologic activity, lipid peroxidation, and cytokine release⁶. This replaces the earlier theory that malnutrition was the primary pathogenic mechanism. The hepatic metabolism of ethanol, which leads to increased oxidative stress in the body, is depicted in Fig. 1. Most of the time, the quantity of alcohol ingested has a direct impact on how long liver disease takes to develop⁷_.

Fig. 1. Hepatic metabolism of ethanol associated with oxidative stress.

Alcoholism over an extended period of time can cause a variety of liver lesions. The earliest and most prevalent reaction, known as fatty liver (also known as steatosis), occurs in over 90% of drinkers who have four to five standard drinks per day. Alcohol-induced liver disease can progress to cirrhosis, fibrosis, hepatocellular carcinoma, and even liver inflammation (steatohepatitis) if drinking is sustained. Comprehending the intricate interplay among diverse hepatic cell types is imperative in comprehending alcohol-induced liver damage⁸_. The primary processes involved in liver fibrogenesis are collagen synthesis and stellate cell activation. The degree of damage to the liver's architecture after long-term alcohol consumption is determined by the fibrosis that follows (Fig. 2).

Fig. 2. Pathogenesis of alcoholic liver disease.

The bidirectional actions involved the integration of genetic, dietary, and environmental factors, which were linked to the liver and gut microbiota axis. The interactions between the gut and liver are explained by changes in the intestinal barrier, which can also occasionally have detrimental effects on the liver. Alcohol consumption is the primary factor linked to the intestinal microbes in hepatic illness. The gut derivatives' mutual reciprocal action enters the liver directly and results in intestinal secretions. Alcohol-induced microbial peptides raise the concentration of proinflammatory mediators in the liver's surrounding environment, which is linked to the gut microbiota, the mucous membrane lining, and the epithelium barrier. Alcohol directly affects the liver parenchymal cells during the development of liver pathogenesis, which starts the abnormalities of intestinal barrier functions, changes the microbiota, and increases the activation of toll-like receptors (TLRs) in the liver cells. in particular, how changes in gut microbiota may contribute to the aetiology of liver disorders⁹_.

Advantages of nanoparticles:

· In proportion to solubility, bioavailability rises. Increases.

· It provides medication delivery that is specific.

· Drug resistance time is lengthened by it.

· Because the polymer used to prepare the nanoparticles is biodegradable, the nanoparticles themselves are less toxic.

· There are several ways to administer it, including parenteral, intraocular, and oral¹⁰_.

· Drug incorporation into the system is simple and doesn't require a chemical reaction.

· Matrix constituents have the ability to modify both the controlled release pattern and degradation characteristics.

Disadvantages of nanoparticle:

· Ostwald ripening: as a result of the high free energy of the nanoparticles, agglomerates or aggregates form.

· More intricate operational process

· Increased likelihood of contamination.

· Because of their smaller size and greater surface area, nanoparticles are very difficult to handle in both liquid and dry forms.

· Because of their smaller size and greater surface area, nanoparticles react strongly with the external

· phase¹¹_.

Applications of nanoparticles:

1. Gene and medication delivery.

2. Engineering of tissues.

3. Identification of proteins.

4. Pathogen biodetection.

5. DNA testing.

6. Heating-induced tumour cell destruction.

Preparation of nanoparticles:

The properties of the drug and polymer determine which preparation technique is best for creating nanoparticles. As a result, the mode of operation is essential to achieving the desired properties. Different techniques are used to create nanoparticles. The choice of method is dependent on the well-defined morphology and structures of the nanoparticles, which include chemical, biological, physical, and physiological factors¹²_.

1. Solvent evaporation method:

It was the original technique for creating nanoparticles. This method used dichloromethane and chloroform to prepare polymer solutions as an emulsion in a volatile solvent. Due to its far superior toxicological profile, ethyl acetate should be used in place of the solvent in order to produce polymeric particles smaller than 500 nm. The preparation process causes the solvent to evaporate, turning the emulsion into a suspension of nanoparticles. After that, let the emulsions, either single or double (like W/O/W), to diffuse.

The double emulsion method requires high-speed homogenization, solvent evaporation, and ultracentrifugation. Continuous magnetic stirring at a regulated temperature or lower pressure produces nanoparticles. Following formation, the product is gathered and put through washing and lyophilization using ultracentrifugation. Techniques for single and double emulsion are frequently employed. Pharmaceutical formulations such as the encapsulation of hydrophilic and hydrophobic anticancer drugs, anti-inflammatory drugs, antibiotic drugs, amino acids, and proteins are made using the solvent evaporation method.

2. Nanoprecipitation:

Using this method, polymers are added to solvents such as acetone, ethanol, or methanol, whether or not a surfactant is present. Next, the poly-lactic acid diffused with this solvent phase. Because PLA has an intermediate polarity, dissolving it in a water-miscible solvent causes nanospheres to form.

Submicron-sized (<210 nm) nanoparticles are produced by nanoprecipitation after polymer injection into the aqueous phase. Use biodegradable polymers to lessen the harmful effects of nanoparticles. The "ouzo effect" refers to the scattering of nanoparticles caused by the absence of surfactant in the solution phase. The low energy input of nanoprecipitation is an advantage¹³_.

3. Emulsification diffusion:

Another name for it is the solvent diffusion method. The modified version of the solvent evaporation technique is called emulsification diffusion. Due to spontaneous diffusion, turbulence is produced in a mixture of water immiscible and water miscible solvents. Consequently, nanoscale particles developed. The rate at which a solvent diffuses on a dispersed phase determines the formation of products. Aqueous solution's oil-polymer ratio and stabiliser presence promote solvent diffusion to the external phase.

The emulsification diffusion technique has the following benefits: high capsulation efficacy, high batch to batch consistency, ease of scaling up, simplicity, and lack of homogenization requirement. Emulsification diffusion was used to create nanoparticles such as doxorubicin-loaded PLA, DNA-loaded PLA, and coumarin-loaded PLA.

4. Salting out:

It is a variation on the diffusion technique for emulsion solvents. The drug and polymer mixture in the solvent is emulsified into an aqueous gel. Salting agents include non-electrolytes (sucrose) and electrolytes (magnesium chloride, calcium chloride, and magnesium acetate). This method's ability to effectively encapsulate medications will change if salting out agents is employed. After the process is finished, the salting out agent is removed via filtration.

5. Dialysis:

It works in a manner akin to nanoprecipitation. It is appropriate for creating narrowly dispersed, tiny nanoparticles. Here, an organic solvent-containing polymer is poured into the dialysis tube. A homogenous suspension of nanoparticles is produced when a polymer aggregates as a result of losing its solubility. A semi-permeable membrane reduces the amount of mixing of the polymer solution by enabling passive solvent transport¹⁴_.

6. Supercritical fluid technology (SCF):

SCF can be used to produce nanoparticles in large quantities. This method has none of the disadvantages of other methods. SCF is a substitute technique for creating biodegradable nanoparticles and microparticles. Eco-friendly is SCF fluid. Since carbon dioxide doesn't cause inflammation or toxicity, it is one of the most commonly used SCF.

Characterization nanoparticles:

1. Particle size:

The two most crucial aspects of nanoparticles are size and shape. Electron microscopy is used. The primary goals of nanoformulations are targeted drug delivery and drug release. It is evident from these data that particle size has an impact on drug release. In order to accelerate the release of the drug by exposing the loaded drug to the particle's surface. During storage, smaller particles have a propensity to foam aggregates. Thus, establishing a connection between stability and reduced particle size. It was discovered that the rate of PLGA degradation increased with particle size. Several additional techniques for determining the size of nanoparticles.¹⁵_.

2. Surface charge (zeta potential):

The zeta potential of nanoparticles provides colloidal stability, and both the magnitude and type of surface charge are significant in determining whether there is any electrostatic interaction between the sample and any interactions with the biological environment. Surface charge is indirectly given by the obtained zeta potential. The potential difference between the outer Helmholtz planes and the shear surface corresponds to the zeta potential. The colloidal dispersion's storage stability is ascertained using the zeta potential. Zeta potential can have a positive or negative value based on whether there is aggregation or stability. The degree of surface hydrophobicity can also be used to determine zeta potential.

3. X-ray diffraction (XRD) analysis:

A common method for figuring out crystallographic morphology and structure is X-ray diffraction. The amount of constituent causes the intensity to change either way. This method is used to determine whether a particle is metallic, provides information on the unit cell's size, shape, and translational symmetry based on Peak positions, and determines the electron density—that is, the location of the atoms within the cell—based on peak intensities¹⁶. X per Rota flex diffraction metre with Cu K radiation and =1.5406 was used to calculate XRD patterns. Size of crystallites is determined using the Scherrer equation:

CS=K / cos

CS stands for crystallite size. The full width at half maximum (FWHM) in radius is constant [K] = 0.94.

[β] = FWHM x π /180λ

Bragg angle = cos. Researchers have looked into X-ray diffraction analysis using different nanoparticles to determine the high crystallinity of the prepared sample.

4. Fourier Transform Infrared (FTIR) Spectroscopy:

It is used to assess the nature of related functional groups and structural characteristics of biological extracts with nanoparticles. It measures infrared intensity vs. Wavelength of light. The computed spectra distinctly show the well-known dependence of the optical properties of nanoparticles. Fourier Transform Infrared [FTIR] Spectroscopy was used to analyse the green synthesised silver nanoparticle using different leaf extracts, and the results revealed characteristic peaks.

5. Scanning electron microscopy (SEM):

Through visual inspection, the surface phenomenon can be measured. The following technique is advantageous for both morphology and sizing analysis. Here, the sample is coated with metals, such as gold, using a sputter coater, after the nanoparticle solution has first been dried into a powder and the sample has been placed in the sample holder. Next, a fine electron beam was used to scan the sample while it was focused. Sample surface characteristics are derived from the secondary electrons that are released from the sample. Nanoparticles were resistant to damage from electron beams in a vacuum, but polymers were not. After that, the mean size determined by SEM and DSC are similar. The time-consuming nature, high expense, and requirement for supplementary size distribution data are drawbacks of SEM¹⁷.

6. Transmission electron microscope:

Similar to the SEM technique, TEM worked on a different principle. It also provides comparable data. However, the preparation of the sample is more difficult and time-consuming than with SEM because ultra-thinness is needed for electron transmission. Distribute nanoparticles across films or a surface grid. Employing negative staining substances such as uranylacetate, phosphotungstic acid or its derivatives, and plastic embedding. Using a similar technique, the sample is exposed to liquid nitrogen in vitreous ice. Transmission of an electron beam to an ultra-thin sample provides surface characteristics¹⁸.

7. Drug release:

Drug loading is the quantity of bound drug per mass of polymer and is expressed as a percentage of the polymer. Analytical techniques like gel filtration, centrifugal ultrafiltration, UV spectroscopy, HPLC, and ultracentrifugation are employed^19,20.

8. Animal study:

For this experiment, thirty-six male Wistar rats will be employed. After purchase, the animals will have seven days to adjust. There will be controls over the temperature (22±2℃) and humidity (45–55%). The animals will be kept in a 12-hour cycle of light and dark. There will be a two-month study period. Six groups of six animals each will be formed from the 36 total animals. For 21 days, all rats—aside from Group I-were oral alcohol-sensitized (40%), consuming 3 millilitres per day.

Groups 3, 5, and 6 will receive the high, medium, and low doses of the test formulation for 21 days in addition to standard treatment and alcohol.

Following a 21-day period, blood will be drawn using ROB of rats for biochemical analyses, including measurements of serum levels of TG, cholesterol, AST, ALT, and ALP. After the animals are sacrificed, their livers are separated and gathered for a histological analysis.

CONCLUSION:

In this NP review, we provided a thorough overview of NP, including their types, preparation techniques, and applications. NPs were found to vary in size from a few nanometers to 500 nanometers through the use of characterization techniques like TEM, XRD, and SEM. Conversely, the morphology is controllable. NPs are a good fit for a wide range of applications due to their large surface area and small size. The size, shape, and characteristics of NP can all be manipulated by the preparation process.

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Received on 14.04.2024 Modified on 01.05.2024

Res. J. Pharma. Dosage Forms and Tech.2024; 16(3):275-279.

DOI: 10.52711/0975-4377.2024.00043