Emerging Phytosynthesized Nanomaterials for Biomedical Applications

By Genevieve Dable-Tupas, Michael K Danquah, Jaison Jeevanandam and 2 more

Emerging Phytosynthesized Nanomaterials for Biomedical Applications provides readers with an increased understanding of the efficacy of phytochemicals obtained from plant extracts for the synthesis of nanomaterials, mechanism of formation, and the development of functional composites, all while still minimizing toxicity to humans and the environment. The book presents various novel biomedical applications of phytosynthesized nanomaterials for cancer, diabetes and cardiovascular treatment, drug delivery, antimicrobial agents, orthopedics, and biosensors, as well as pharmaceutical product development. This is an important reference source for biomaterials scientists and plant scientists looking to increase their understanding of how photosynthesized nanomaterials can be used in biomedical applications.

• Outlines the significance of phytochemicals in nanomaterial biosynthesis for sustainable applications
• Explores the efficiency of phytosynthesized nanomaterials in various biomedical applications, including cancer, diabetes and cardiovascular ailment treatment, drug delivery, antimicrobial agents, orthopedics and biosensors
• Assesses the potential limitations of phytosynthesized nanomaterials and ways to mitigate these challenges for emerging applications, including wound healing plasters, nanorobots, artificial organs and antimicrobial textiles

• Language: English
• Publisher: Elsevier Science
• Release date: Feb 10, 2023
• ISBN: 9780128243947

Genevieve Dable-Tupas

Genevieve Dable Tupas, MD, MMCE, FPPS, FPSECP is an Associate Professor at the Research Center, College of Medicine, Davao Medical School Foundation, Inc, Davao City, Philippines. Her research interests include natural products research, clinical epidemiology, and their translation to benefit the community.

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1: Phytochemical-based approaches for the synthesis of nanomaterials

Jaison Jeevanandam    CQM—Centro de Química da Madeira, MMRG, Universidade da Madeira, Funchal, Portugal

Abstract

The synthesis of nanomaterials plays a crucial role in determining their properties for desired applications. In general, nanomaterial synthesis approaches are classified into physical, chemical, or biological methods, depending on the type of reducing agent utilized for the formation of nanosized particles. Biological approaches rely on the use of biomolecules extracted from microbes and plants as alternative reducing agents, for the formation of nanoparticles. Among biological approaches, microbial extract mediated synthesis has been identified to be time-consuming and with scale-up challenges, compared to plant extract facilitated synthesis. Hence, this chapter presents an overview of plant extract mediated (or phytosynthesis) nanomaterial synthesis. In addition, the effect of extraction methods on the formation of distinct nanomaterial types is discussed.

Keywords

Nanomaterials; Phytochemicals; Functional group; Biomolecules; Stabilizing agent

1.1: Introduction

Nanomaterials have gained significance as next-generation materials for various applications (Jeevanandam et al., 2018a, b). In general, nanomaterials are defined as materials with size 1–100 nm (1–1000 nm in certain cases), and possess different properties compared to their bulk counterparts (Barhoum et al., 2022). The differences in the properties of nanomaterials are attributed to the high surface-to-volume ratio and their surface functionalities. Nanomaterials are widely employed in electronic, electrical, biomedical, and environmental remediation applications (Sajid and Płotka-Wasylka, 2020). The synthesis of nanomaterials plays a crucial role in determining their properties for specific applications. Nanomaterial synthesis approaches can be broadly classified into top-down, where bulk (macro- or microsized) materials are reduced into nanomaterials (Sajid, 2021), and bottom-up, where atoms or molecules are assembled to form nanosized particles (Khan, 2020). Advancements in nanoscience have led to the development of a subclass in these synthesis types for the formation of stable, less toxic, and monodispersed nanoparticles (Shah et al., 2021).

Nanomaterial synthesis approaches are classified into physical, chemical, or biological methods, depending on the type of reducing agent utilized in the synthesis process (Jamkhande et al., 2019). Physical approaches are mostly top-down, whereas chemical and biological methods are mostly bottom-up. Physical methods, such as laser ablation (Wang et al., 2021), sputtering (Kim et al., 2021), and ball-milling (Kim et al., 2021), are useful in generating nanoparticles with good stability. However, high equipment cost, inability to maintain monodispersity, and smaller possibility of yielding other-than-spherical nanoparticles are some of the limitations of physical methods (Jeevanandam et al., 2016). Chemical approaches, such as sol-gel (Ismail et al., 2019), hydrothermal (Gan et al., 2020), polyol (Hemmati et al., 2020), and coprecipitation (Radoń et al., 2018), are beneficial in yielding monodispersed nanoparticles, with an additional advantage of transforming their morphology for tailored applications (Verma et al., 2019). However, limitations such as the usage of hazardous chemicals as reducing agents, which eventually increase the toxicity of the generated nanomaterials, continue to be a hurdle for chemical-based approaches (Andra et al., 2019). Biological approaches rely on the use of biomolecules extracted from microbes and plants as an alternative reducing agent, compared to synthetic chemicals, for the formation of nanoparticles (Jadoun et al., 2021; Sardar and Mazumder, 2021). Among biological approaches, microbial extract mediated synthesis has been identified to be time-consuming with scale-up challenges, compared to plant extract facilitated synthesis (Sardar and Mazumder, 2021). This chapter presents an overview of the steps involved in the plant extract mediated synthesis (phytosynthesis) of nanomaterials. In addition, the effect of extraction methods on the formation of distinct nanomaterial types is discussed.

1.2: Phytosynthesis of nanomaterials

Plants contain various phytochemicals that can be classified into phytosterols, alkaloids, polyphenols, terpenoids, and organosulfur compounds (Bayir et al., 2019). In addition, polysaccharides, proteins, vitamins, and certain specific phytocompounds are present in plant extracts (Raina et al., 2008; Ghaly et al., 2010; Wen et al., 2012; Işık et al., 2014). All these phytochemicals and phytocompounds act beneficially as reducing and stabilizing agents for the formation of nanoparticles (Shaheen and Ahmad, 2020). Phytosynthesis of nanoparticles is carried out via four stages: reduction, nucleation, growth, and stabilization (Dhamecha et al., 2016). The type of phytochemical used is important, as it affects these four stages through reaction with the precursor to form the nanoparticles (Ahmad et al., 2019). The optimization of process parameters plays a crucial role in the fabrication of nanoparticles with specific morphology (Nasar et al., 2019; Ekaji et al., 2021). Temperature, reaction time, quantity of extract, and other parameters, including pH and pressure, affect the synthesis of nanoparticles with desirable morphology and surface functional groups (Surendra et al., 2016; Arya et al., 2018; Hasnain et al., 2019; Jeevanandam et al., 2019a, 2019b). Moreover, usage of other energy sources such as microwave, ultrasound, and photo (visible, ultraviolet, or infrared rays) is gaining significant interest as an alternative to thermal for nanoparticle synthesis (Lopes and Courrol, 2018; Bayrami et al., 2019). The final step in the formation of nanoparticles is purification, where the biomolecular surface functional groups that served as reducing and stabilizing agents are reduced to yield pure nanoparticles (Dauthal and Mukhopadhyay, 2016). However, the elimination of surface functional groups may lead to agglomeration and increase their toxicity, similar to chemically synthesized nanoparticles (Jeevanandam et al., 2020).

1.3: Phytochemical extraction methods

The first step in the phytosynthesis of nanoparticles is the extraction of phytochemicals from plants. The step can be performed via maceration, percolation, Soxhlet, ultrasound, microwave-assisted, supercritical fluid, and accelerated solvent extraction methods, as shown in Fig. 1.1.

Fig. 1.1

Fig. 1.1 Methods for the extraction of phytochemicals from plants.

1.3.1: Maceration

Maceration is one of the most common methods to extract the phytochemicals from plant parts, especially from bark and leaves, with the help of solvents. In this method, the selected plant part must be dried and coarsely powdered. The powder is then placed in a container and closed for at least 3 days with periodic stirring required. Later, the phytochemicals can be separated from the plant powder via a filtration or decantation process (Abubakar and Haque, 2020). Rajabi et al. (2017) fabricated zinc oxide (ZnO) nanoparticles using the phytochemicals extracted from the leaves of Suaeda aegyptiaca via the maceration process. The resultant ZnO nanoparticles were identified to be spherical and ∼80 nm in size, with polydispersity (Rajabi et al., 2017). Likewise, Abdullah et al. (2020) recently demonstrated the synthesis of iron oxide nanoparticles using the leaves of Phoenix dactylifera to extract phenolic compounds via the maceration process. The study showed that iron chloride was utilized as a precursor, and was mixed with the extracts for 1 h at 70°C to form nanoparticles. The results revealed the formation of iron oxide nanoparticles in two crystal forms (Fe2O3 and Fe3O4) with a spherical morphology of 12.61 nm (average size) along with agglomerated uniform flower-like features (Abdullah et al., 2020). Similarly, Martínez-Flores et al. (2021) utilized the maceration process for the extraction of phytochemicals from Pleurotus ostreatus and Pleurotus djamor mushrooms for silver nanoparticle synthesis. In this study, a cabinet oven-drying method and solar dehydration were used to dry the mushrooms and different concentrations of water mixed with ethanol were used as the solvent, at a temperature of 25°C with constant stirring over 48 h. The study emphasized that the maceration process with 100% water and solar dehydration led to the extraction of phytochemicals from P. ostreatus and P. djamor with high antioxidant activities, and was beneficial in the synthesis of silver nanoparticles of sizes 28.44 and 55.76 nm, respectively (Martínez-Flores et al., 2021). However, although this method can lead to the extraction of phytochemicals for the fabrication of nanoparticles with distinct shape and size, the lack of control over process parameters is a major limitation of this approach (Bryda and Stadnytska, 2021).

1.3.2: Percolation

Percolation is a distinct exhaustive phytochemical extraction process, in which the soluble compounds are eliminated from the plant source, via fresh solvent extraction. Percolation is usually followed by repercolation, where the percolate is reintroduced as a solvent to reduce solvent consumption (Mukherjee, 2019). Komal and Kashyap (2018) extracted phytochemical paste from the fruit of Actinidia deliciosa via a hot percolation approach using distilled water and ethanol (70% pure) as solvents. The results revealed the formation of ∼38-nm and ∼48-nm silver nanoparticles with spherical morphology (Komal and Kashyap, 2018). Further, Saadatmand et al. (2021) fabricated zinc nanoparticles using the phytochemicals from the aerial part of Lavandula angustifolia via a percolation system with 80% of methanol at 21°C for 72 h. The extracted compounds were mixed with zinc sulfate as a precursor for the formation of spherical and polydispersed zinc nanoparticles of size 30–80 nm (Saadatmand et al., 2021). Furthermore, silver and gold nanoparticles were synthesized using the phytochemicals from the leaves of Crataegus monogyna, extracted via a percolation approach. In this study, methanol was used as a solvent to extract phytochemicals from the leaf at room temperature and was mixed with the metal precursors, including silver nitrate and gold chloride, to form spherical, homogeneous, and monodispersed silver and gold nanoparticles of size 55–70 nm and 50–60 nm, respectively (Shirzadi-Ahodashti et al., 2020). Even though this method is beneficial in yielding monodispersed nanoparticles, the requirement of longer extraction time and the high volume of solvent required serve as limitations of the percolation method (Azwanida, 2015).

1.3.3: Soxhlet extraction

The Soxhlet extraction approach has been widely used to extract thermally stable analytes. In this method, the extraction solvent is in a continuous cycle in a matrix via boiling and condensation, and the phytochemicals are collected in the hot solvent (Ridgway et al., 2012). Aguilar et al. (2018) utilized the Soxhlet approach for the extraction of biomolecules in sugarcane bagasse from sugar industry waste, to use them as a reducing agent for the synthesis of silver nanoparticles. The extracted biomolecules were mixed with silver nitrate precursors for the fabrication of spherical and semispherically shaped silver nanoparticles in the size range of 6–36 nm (Aguilar et al., 2018). Similarly, Alrajhi et al. (2021) prepared ZnO nanoparticles using the phytochemicals extracted from the leaf powder of Salvia officials via the Soxhlet approach. The leaf powder in the Soxhlet apparatus was boiled for 1 h to turn the color to yellow, and 3 h of extraction led to a transparent mixture of phytochemicals as a reducing agent for the synthesis of tubular hexagonal-like ZnO nanoparticles of ∼150 to 800 nm (Alrajhi et al., 2021). Likewise, Ahmad et al. (2020) reported the synthesis of titanium dioxide nanoparticles using the phytochemicals extracted from the leaves of Mentha arvensis via the Soxhlet method. In this study, the leaves of the plant were dried at room temperature for 7 days and then converted into dried powder, which was added in the Soxhlet apparatus with 250 mL of ethanol at 50°C for phytochemical extraction after 8 h. The resultant ethanolic extract was identified to contain alkaloids, phenolics, terpenoids, proteins, and carbohydrates, and was used as a reducing agent for the formation of spherical nanoparticles of size 20–70 nm (Ahmad et al., 2020). This method is highly effective for the extraction of a high concentration of phytochemicals from a plant source. However, it is beneficial to extract thermally stable phytochemicals, and the alteration of pH in the Soxhlet apparatus can reduce the effectiveness of the extracted biomolecules (López-Bascón and De Castro, 2020).

1.3.4: Ultrasound-assisted extraction

This method uses ultrasound waves of low frequency and high power coupled with the slurry of plant material in a solvent to achieve the extraction of phytochemicals (Louie et al., 2020). Deshmukh et al. (2019) fabricated silver and iron oxide nanoparticles using the phytochemicals from fenugreek seed extract via an ultrasound-assisted approach. In this method, which is the conventional approach of extraction, the fenugreek seeds were washed with water and oven-dried for 1 h at 80 °C. Later, the seeds were crushed into powder, mixed with water, and boiled for 1 h at 100°C under reflux conditions. The extracted phytochemicals were used for the formation of ∼20 nm-sized, quasispherical, and monodispersed nanoparticles with the assistance of ultrasound via probe sonicator for 15 min (Deshmukh et al., 2019). Further, Moradi Alvand et al. (2019b) synthesized cadmium telluride quantum dots using the phytochemicals extracted from powdered Ficus johannis fruit via an ultrasound-assisted extraction approach. The resultant extracts were identified to possess phenols, flavonoids, and antioxidants and are utilized as a reducing agent for the fabrication of spherical quantum dots with average particle size of 3.7 nm (Moradi Alvand et al., 2019a, b). Moreover, Alomari (2020) utilized an ultrasound-assisted method for the extraction of flavonoid, phenolic, and antioxidant compounds from the leaves of the Dodonaea viscose plant. The extracted phytochemicals were used for the fabrication of polydispersed spherical silver nanoparticles with a size of ∼30 nm (Alomari, 2020). Even though this method is highly beneficial in extracting specific phytochemicals for nanoparticle fabrication, poor purity, low efficiency, and longer reaction times are the limitations of the ultrasound extraction method (Aihua et al., 2019).

1.3.5: Microwave-assisted extraction

A microwave-assisted extraction is a conventional approach for isolating and extracting active phytochemicals from plants by utilizing microwave energy to heat solvents for the isolation of analytes from a matrix of the sample and solvent (Llompart et al., 2019). Recently, Abdullah et al. (2020) utilized a microwave-assisted extraction method for the extraction of phytochemicals from the aqueous leaf mixture of Dodonaea viscose. The extracted crude phytochemicals were used for the synthesis of spherical, cylindrical, and irregular-shaped gold nanoparticles with a diameter of 6–80 nm (Tyal-Abdullah et al., 2020). Likewise, Rehan et al. (2020) demonstrated the extraction of phytochemicals and volatile compounds from the red Arachis hypogaea (peanut) skin via a microwave-assisted approach. In this method, solvents such as hexane, water, and ethanol in a liquor ratio of 1:30 were used to extract 14 phenolic compounds and 7 flavonoid compounds by microwaving for 30 min. The extracted phytochemicals were used for the simultaneous dyeing and incorporation of silver nanoparticles of near-spherical, 35–70 nm-sized silver nanoparticles in the viscose fibers (Rehan et al., 2020). Also, Alvand et al. (2019) fabricated zinc telluride quantum dots using the phytochemicals extracted from the fruit of Ficus johannis plant using a microwave-assisted extraction approach of 90 or 270 W for 15 min. The crude aqueous extract was used for the fabrication of spherical quantum dots of ∼8 nm in size (Moradi Alvand et al., 2019a, 2019b). This method is highly significant in controlling the process parameters to yield monodispersed nanoparticles of desired morphology. However, the major limitation of this method is the high maintenance cost when utilized on a commercial scale (Chandra et al.,