Microwave-Assisted Synthesis of Selenium Nanoparticles:

A Comprehensive Review on Optimizing Parameters for Enhanced Bioavailability and Therapeutic Potential

 

Amir Mohamed Abdelhamid1,2, Lashin Saad Ali3,4, Hoda A. Fansa5,6,

Ahmed S.G. Srag El-Din7,8*

1Department of Clinical Pharmacy, College of Pharmacy, Almaaqal University, 61014 Basrah, Iraq.

2Department of Pharmacology, Faculty of Pharmacy,

Delta University for Science and Technology, Gamasa 11152, Egypt.

3Department of basic medical science-faculty of dentistry- Al-Ahliyya Amman university-Amman-Jordan.

4Physiology Department-Mansoura faculty of Medicine Mansoura university-Mansoura-Egypt.

5Associate Professor of Oral Biology, Faculty of Dentistry, Al -Ahliyya Amman University, Jordan.

6Assistant Professor of Oral Biology, Faculty of Dentistry, Alexandria University, Egypt.

7Department of Pharmaceutics, College of Pharmacy, Almaaqal University, 61014 Basrah, Iraq.

8Department of Pharmaceutics, Faculty of Pharmacy,

Delta University for Science and Technology, Gamasa 11152, Egypt.

*Corresponding Author E-mail: ashawkey@yahoo.com

 

ABSTRACT:

Selenium is an essential trace element with significant biochemical and therapeutic properties, including antioxidants, immunomodulatory, and detoxifying activities. Despite its benefits, traditional forms of selenium face limitations in bioavailability, solubility, and a narrow safety window. Selenium nanoparticles have emerged as a promising alternative due to their enhanced bioavailability, lower toxicity, and versatile biological activities. Among various methods for Selenium nanoparticles synthesis, microwave irradiation has gained attention for its efficiency, uniform heating, and high yield. This review focuses on the preparation of Selenium nanoparticles using the microwave-assisted technique and examines the critical factors influencing their synthesis. Key parameters include the concentration of selenite salt, concentration of reducing agent, surfactant concentration, reaction time, and temperature, all of which play pivotal roles in determining the size, morphology, stability, and crystallinity of the resulting nanoparticles. Higher concentrations of selenite salt typically led to increased particle size and decreased stability, while the concentration of reducing agents directly impacts the reduction kinetics and nanoparticle properties. Surfactant concentration is crucial for controlling nanoparticle surface properties and stability, influencing interactions within the synthesis environment. Reaction time and temperature significantly affect nucleation, growth processes, crystallinity, and polymorph formation. Optimizing these factors is essential for tailoring Selenium nanoparticles with desirable attributes for diverse applications, particularly in biomedical and industrial sectors. This review emphasizes the importance of precise control over synthetic parameters in the microwave-assisted method, providing insights into the production of Selenium nanoparticles with enhanced functionalities.

 

KEYWORDS: Selenium, Selenium nanoparticles, microwave irradiation, antioxidant, crystallinity.

 

 


INTRODUCTION: 

Selenium (Se) is widely used in a variety of fields due to its distinct chemical, physical, and biochemical properties. It is regarded as one of the most important trace elements for human health because it acts as the active site of Se-dependent enzymes such as peroxidase, iodothyronine deiodinase, and thioredoxin reductase. Se's target role is to protect cells from oxidation by activating antioxidative defenses1-4. Se is commonly utilized as a dietary supplement5-7, It may also be used to prevent various diseases, including cardiovascular disease, arthritis, muscular dystrophy, and cystic fibrosis 8. Furthermore, it plays a significant role in immunity and cancer9. Se compounds are thought to be detoxifying agents, acting as antagonists against mercury10-16 , methylmercury17-20, cadmium21-24, silver 25, lead26, and many other elements9. Selenium's interactions with other hazardous elements in living organisms are still being investigated27-30.

 

Se  can be found in the environment and in living organisms, ranging from simple inorganic forms (e.g., selenides, halides, oxyhalides, oxides, acids, and salts of the oxyacid) to the complex biogenic compounds such selenoenzymes and selenium nucleic acids31. Selenium biogenic compounds are classified into large families that include simple organic and methylated species, seleno-amino acids, seleno-proteins, seleno-enzymes, seleno-amino-carboxylic acids, selenium peptides, and selenium derivatives of pyrimidine, purine, cholines, steroids, coenzyme A, and many others. Most of these forms play a role in living organisms and have biological functions by contributing to reduction of oxidative stress32. The main problem of most of these organic and non-organic forms is their low bioavailability, and low solubility. Furthermore, Se has  a narrow safety window and its biological activity is dependent upon its chemical form since different Se forms have different metabolic pathways8.

 

Selenium nanoparticles (SENPs) have recently been identified as a potential source of this element33-35. SENPs, like other nanoparticles, have significant chemical, physical, and biological properties and exhibit unique functionalities due to their nanoscale size.  These characteristics are linked to the lower surface area per unit volume of SENPs, which results in less interactive nanoparticles that release selenium more slowly. Furthermore, the ability to function with a variety of ligands increases their affinity for targets. Nanoparticles' surface properties, such as surface charge density and surface hydrophobicity, are thought to be critical to their activities. SENPs exhibits higher bioavailability, stronger biological activity, and lower toxicity when compared with other selenium forms such as selenate, selenious acid, Sodium Selenite, selenomethionine and methylselenocysteine.33,36. With all these advantages, SENPs are a promising candidate for replacing other forms of Se in clinical practice.

 

There are several methods that is used to prepare SENPs including chemical, physical, and biological techniques. However, the aim of the current review is to study factors affecting SENPs prepared by Microwave irradiation method.

 

Preparation of SENPs by microwave irradiation technique:

Microwave irradiation is an efficient physical technique that is used for synthesis of nanoparticles37-42.  In this method, microwave energy is applied to heat the reaction mixture uniformly and rapidly, leading to the formation of nanoparticles through direct interaction with the molecules, leading to a corresponding reduction in the reaction rate43,44. The benefits of using microwave irradiation include faster reaction times, improved particle size control, uniform heating, energy efficiency, and high yield45. This method also often results in nanoparticles with enhanced purity and fewer byproducts due to the precise control over reaction conditions making it an attractive green synthesis route 46. SENPs prepared by Microwave irradiation employ heating selenium salts and reducing agent in aqueous solution at microwave oven for a certain power and certain time (Figure 1). Several studies have explored the synthesis of SENPs using microwave-assisted methods. These studies have demonstrated the successful synthesis of SENPs with controlled particle sizes, stable crystalline structures, and various polymorphs.  A study by Fardsadegh, Vaghari et al.47 used SeCl4 as the source to synthesize black SENPs via microwave-assisted reduction with hydrazine and the surfactant SDS. After exposing the solution to microwave irradiation for 4-5 minutes at 750 W, black SENPs were formed. The resulting nanoparticles were found to be stable, with narrow size distributions and high crystallinity

 

 

Figure 1: Schematic representation of the microwave-assisted synthesis of selenium nanoparticles (SeNPs). The process involves the use of an aqueous solution containing selenium precursor (e.g., selenite salt) and a reducing agent, exposed to microwave irradiation under controlled temperature and time conditions.

 

Zhu, Palchik et al.48 synthesized various metal chalcogenide nanoparticles using a microwave-assisted approach. They mixed the appropriate metal salts and selenide precursor in a solvent and then heated the mixture in a microwave reactor. The authors found that the microwave-assisted approach resulted in the formation of nanoparticles with narrow size distributions and high crystallinity, and that the optimal reaction conditions varied for each material. The CdSe and PbSe nanoparticles had hexagonal shapes, while the Cu2-xSe nanoparticles had spherical shapes and were found to be copper-deficient. The synthesized nanoparticles exhibited good photoluminescence properties, making them potentially useful in a range of applications such as solar cells, sensors, and optoelectronics.

 

Several factors affecting formation of the SENPs prepared by microwave irradiation technique including the concentration of selenite salt, concentration of reducing agent, surfactant concentration., reaction time, and temperature.  Optimization of these factors influences the characteristics of the synthesized SENPs.

 

Factors affecting SENPs prepared by microwave irradiation technique:

1. The concentration of selenite salt:

The concentration of selenite salt is a critical factor that influences the synthesis of SENPs. Selenite salt serves as the source of selenium ions that participate in the reduction reaction to form nanoparticles. Altering the concentration of selenite salt has a direct impact on the synthesis process, leading to changes in the size and morphology of the resulting nanoparticles. It was reported that higher concentrations of selenite salt typically result in an increased particle size and decrease the stability of SENPs because of increase the supply of selenium ions, which promotes nucleation and growth of the nanoparticles. Consequently, this often leads to the formation of larger-sized nanoparticles1,49-51. Conversely, lower concentrations of selenite salt provide a limited supply of selenium ions, which can restrict the nucleation and growth process, resulting in smaller-sized nanoparticles and increase the stability of the SENPs 37,52.  Additionally, variations in the concentration of selenite salt can affect the morphology of the synthesized nanoparticles. Different concentrations can influence the kinetics of the reduction reaction, leading to the formation of nanoparticles with diverse shapes, such as spherical, rod-like, or irregular morphologies53,54.

 

2. The concentration of the reducing agent:

The concentration of the reducing agent, the reducing agent is responsible for the reduction of the selenium precursor, such as selenite salt, to form SENPs. By adjusting the concentration of the reducing agent in the synthesis process, researchers can control the reduction kinetics and, subsequently, the size and properties of the nanoparticles. Several studies evaluated the influence of using reducing agents during the synthesis of SENPs, concluded that increasing the concentration of reducing agents more than the concentration of the metal precursor provide nanoparticles with smaller particle size37,55-57. According to studies by Ahmadi et al. and Eskandari-Nojedehi et al., the concentration of the formed silver and gold NPs increased when the amounts of Aloe vera leaf extract and mushroom extract were increased at lower amounts of silver and gold salts58,59.

 

Another study conducted by Sheikhlou, Allahyari et     al. 57 used 15–25mL of sodium selenite solution and 1–5 mL of walnut leaf extract as reducing agent that were mixed and  heated using a domestic microwave oven  at fixed power and exposure time of 800W and 4min, respectively concluded that increasing walnut leaf extract from 1 to 5ml was associated with increasing the UV absorbance of SENPs which indicate higher amount of SENPs as the concentration of bio reductants, existing in the extract increased, reduce more amounts of the selenium ions into the SENPs. Also, the study concluded that microwave radiation effectively accelerated the fabrication of Se NPs within minimum processing time. The short preparation time was explained by the effect of electrical charges of microwave electric field.

 

3. Concentration of surfactants:

Surfactants play a crucial role in the synthesis and stabilization of SENPs. They are commonly employed to control the growth, shape, and stability of nanoparticles during the synthesis process. In a study where microwave irradiation is utilized as a synthesis method for SENPs by employing selenium salts in an aqueous solution as the starting material. SENPs can be formed by heating the solution at 750W for 4 minutes without the use of surfactants. In this procedure, larger aggregates of SENPs with sizes ranging from approximately 200 to 800nm are obtained, along with a high percentage of agglomeration. However, when sodium dodecyl sulfate is applied, the particles exhibit a smaller size and higher homogeneity. Conversely, the use of polyethylene glycol 600 and cetyltrimethylammonium bromide leads to an increase in particle size and a decrease in homogeneity. Transmission electron microscopy analysis confirmed that the particle sizes ranged from approximately 5 to 25 nm60. A similar trend was observed in another report, SeCl4 was taken as the source, reduced using hydrazine, where the polymer Sodium dodecyl sulfate was used as the surfactant, and exposed to microwave irradiation for 4–5 minutes at 750 W to obtain black SENPs47.

 

The concentration of surfactants used in the synthesis can significantly influence the surface properties and stability of selenium nanoparticles. The addition of surfactants at different concentrations can modify the interaction between the nanoparticles and the surrounding environment. At lower surfactant concentrations, the nanoparticles may have higher surface energy, leading to increased aggregation and instability61,62. On the other hand, higher surfactant concentrations can provide a greater coverage of the nanoparticle surface, reducing the surface energy and preventing particle aggregation63,64. The concentration of surfactant affects the growth and stabilization of selenium nanoparticles by controlling the adsorption and desorption of surfactant molecules onto the nanoparticle surface65,66. This interaction can influence the nucleation, growth, and subsequent particle size distribution. Furthermore, the surfactant concentration can impact on the surface charge and hydrophilicity/hydrophobicity of the nanoparticles, thereby affecting their stability in different solvents or environments67-69. By adjusting the concentration of surfactant during the synthesis, researchers can tailor the surface properties and stability of selenium nanoparticles. This control allows for the optimization of nanoparticle size, shape, dispersibility, and colloidal stability. It is essential to carefully optimize the surfactant concentration to achieve the desired properties and ensure the long-term stability of the synthesized selenium nanoparticles.

 

4. Reaction time:

The time of reaction is an important parameter in the synthesis of SENPs. The duration of the reaction directly influences the growth and size of the nanoparticles formed. In general, longer reaction times allow for more extensive nucleation and growth processes, leading to the formation of larger nanoparticles. During the reaction, the precursor ions or molecules undergo various chemical reactions and transformations that result in the formation of nanoparticles.  With increased reaction time, there is more time for these processes to occur, allowing for the aggregation and coalescence of nanoparticles, leading to their growth. On the other hand, shorter reaction times may favor the formation of smaller nanoparticles. This is because the limited time available for nucleation and growth restricts particle growth and favors the formation of nuclei with smaller sizes. As a result, the overall size distribution of nanoparticles obtained from a shorter reaction time tends to be smaller and more uniform.  A study conducted by Mellinas, Jiménez, et al.37 used microwave heating and Theobroma cacao L. bean shells as a reducing and stabilizing agent for synthesis of SENPs. Using a central composite design technique, they were able to determine the ideal reaction conditions, which produced particles with a diameter of 42nm: 15.6min, 788.6W, 0.14g of Na2SeO3, and 50mL of Theobroma cacao L. bean shell extract solution. The two-month-old, uniformly distributed, spherical particles with a diameter of 1-3nm were visible in the TEM images.

 

Microwave irradiation time was found to affect the particle size. A study conducted by Yu et al. produced various Se nanostructures, including nanoballs, nanotubes, and multiarmed nanorods by reducing H2SeO3 with L-asparagine in polyethylene glycol solution. At 100°C, the reaction was supported by microwave irradiation. The ratio of L-asparagine to H2SeO3 and the time of microwave irradiation controlled the diameter and morphology of SeNPs. It was reported that Increasing reaction time resulted in SENPs with a larger diameter, which aggregated after 15 minutes of microwave treatment70

 

Furthermore, the reaction time can also influence the crystallinity and phase composition of the synthesized nanoparticles. Longer reaction times may allow for the formation of more well-defined crystalline structures, while shorter reaction times can result in the formation of amorphous or less crystalline nanoparticles. A study reported by Jadhav and Khanna et al. used cycloocteno-1,2,3-selenadiazole as a precursor in diphenyl ether, with oleic acid as a surfactant, to synthesize red and black SENPs using microwave energy. The formation of the red SENPs was confirmed in 10-12 minutes by a UV-absorption band at 400nm, while black Se particles were formed after a few more minutes with a band shift to 490nm. The reaction produced stable, crystalline SENPs with a narrow size distribution, and the SENPs exhibited two different polymorphs, trigonal and monoclinic. The polymorphic forms of Se were confirmed through XRD measurements, with trigonal structure for red Se and monoclinic structure for black Se. The authors investigated the effects of reaction time, temperature, and power on the formation of SENPs and their polymorphs, determining that shorter reaction times and higher temperatures favored the formation of the trigonal polymorph 52.   In summary, the reaction time is a crucial parameter in SENPs synthesis. Longer reaction times tend to produce larger nanoparticles, while shorter reaction times favor the formation of smaller nanoparticles. Optimizing the reaction time is essential to control the size, size distribution, and crystallinity of the synthesized selenium nanoparticles for specific applications.

 

5. The reaction temperature:

The reaction temperature plays a significant role in determining the rate of reaction, as well as the nucleation and growth processes involved in nanoparticle formation71,72. The temperature at which the synthesis takes place affects the kinetics of the reaction. Generally, higher temperatures accelerate chemical reactions by providing more energy to the reactant molecules, leading to increased reaction rates73,74. This can influence the nucleation and growth of nanoparticles, as higher temperatures promote more rapid formation of nuclei and their subsequent growth. Variations in reaction temperature can also have a significant impact on the size, crystallinity, and polymorphs of the synthesized selenium nanoparticles. Higher temperatures can result in larger particle sizes due to increased nucleation and growth rates. On the other hand, lower temperatures may favor the formation of smaller nanoparticles due to slower nucleation and growth processes61,63,64,66,75,76.

 

In addition to size, the reaction temperature can influence the crystallinity of the nanoparticles. Higher temperatures generally promote the formation of more crystalline structures, while lower temperatures may result in the production of nanoparticles with amorphous or less ordered structures77-79. Moreover, the reaction temperature can influence the formation of different polymorphs of selenium nanoparticles. Polymorphism refers to the ability of a material to exist in multiple crystal structures. Varying the reaction temperature can lead to the formation of different polymorphs of selenium nanoparticles, each with unique properties and characteristics. Optimizing the reaction temperature is crucial to controlling the size, crystallinity, and polymorphs of the synthesized selenium nanoparticles for specific applications. It is important to note that the reaction temperature should be carefully selected to balance the desired nanoparticle properties with the limitations imposed by the stability and reactivity of the reactants and reaction environment. In summary, the reaction temperature is a critical factor in nanoparticle synthesis, including the synthesis of selenium nanoparticles. It influences the rate of reaction, nucleation, and growth processes, as well as the size, crystallinity, and polymorphs of the nanoparticles. Careful control and optimization of the reaction temperature are necessary to achieve the desired properties and characteristics of the synthesized selenium nanoparticles.

 

CONCLUSION:

From the previous review it can be concluded that the precise optimization of key synthetic parameters significantly influences the physicochemical properties of SENPs synthesized using the microwave-assisted technique. Variables such as selenite salt concentration, reducing agent ratio, surfactant concentration, reaction time, and thermal conditions during microwave irradiation all play important roles in determining nanoparticle morphology, size distribution, and stability. Tailoring these parameters allows for fine-tuning of SENP properties, resulting in greater control over their formation and potential applications in a variety of biomedical and industrial sectors. Thus, optimizing these factors is critical for creating SENPs with desirable attributes and functionality.

 

CONFLICT OF INTEREST:

The authors declare that there is no conflict of interest

 

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Received on 02.10.2024      Revised on 16.01.2025

Accepted on 14.03.2025      Published on 02.05.2025

Available online from May 07, 2025

Research J. Pharmacy and Technology. 2025;18(5):2003-2009.

DOI: 10.52711/0974-360X.2025.00286

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