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1M. Pharm Scholar Bhavdiya Institute of Pharmaceutical Sciences and Research, Faizabad
2Assistant Professor at Bhavdiya Institute of Pharmaceutical Sciences and Research, Faizabad
The micro-organism-mediated nanoparticle synthesis is of great importance in the nano-field due to its economic viability, higher and easy bioaccumulation and the process can be scaled up relatively easily. The downstream processing and biomass handling are also facilitated. It is also known to occur naturally. In the current study, the biological synthesis of silver nanoparticles (AgNPs) using Bacillus nakamurai sp. (isolated from soil) is reported. The as-synthesized nanoparticles were characterized using X-ray diffraction to confirm AgNP formation. Antibacterial activity of zinc oxide nanoparticles (ZnO-NPs) has received significant interest worldwide particularly by the implementation of nanotechnology to synthesize particles in the nanometer region. Many microorganisms exist in the range from hundreds of nanometers to tens of micrometers. ZnO-NPs exhibit attractive antibacterial properties due to increased specific surface area as the reduced particle size leading to enhanced particle surface reactivity. ZnO is a bio-safe material that possesses photo-oxidizing and photocatalysis impacts on chemical and biological species. This review covered ZnO-NPs antibacterial activity including testing methods, impact of UV illumination, ZnO particle properties (size, concentration, morphology, and defects), particle surface modification, and minimum inhibitory con centration. Particular emphasize was given to bactericidal and bacteriostatic mechanisms with focus on generation of reactive oxygen species (ROS) including hydrogen peroxide (H2O2), OH- (hydroxyl radicals), and O2-2 (peroxide). ROS has been a major factor for several mechanisms including cell wall damage due to ZnO-localized interaction, enhanced membrane permeability, internalization of NPs due to loss of proton motive force and uptake of toxic dissolved zinc ions. More than a billion people worldwide suffer from chronic periodontitis. The primary etiological factor of periodontal diseases is dental plaque and the bacteria it contains, particularly Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans. Zinc, owing to its antibacterial properties, can be employed in periodontology. A systematic review protocol of scientific literature was designed following PRISMA recommendations. Data search was conducted in PubMed, Web of Science, and ScienceDirect databases.
Zinc is a metal found in the Earth‘s crust. It is an irreplaceable and essential element for human health. Approximately 60% of zinc is located in muscles; 30% in bones; and the remaining 10% in skin, hair, pancreas, kidneys, and blood plasma. Intracellularly, it is found in the cytoplasm, vacuoles, organelles, and nucleus. As one of the essential elements and the second most widely distributed chemical element in the human body after iron, it supports the optimal functions of organisms by catalyzing enzyme activity, contributing to the protein structure, and regulating gene expression. Zinc plays a vital role in immune reactions and both cellular and humoral immunity. [1-2] This trace element is necessary for human health, and its deficiency can lead to various diseases. Zinc is also present in the oral cavity, found in saliva, dental plaque, and enamel hydroxyapatites. Zinc oxide, with its unique physical and chemical properties, such as high chemical stability, high electrochemical coupling coefficient, broad range of radiation absorption and high photostability, is a multifunctional material. [3] The piezo- and pyroelectric properties of ZnO mean that it can be used as a sensor, converter, energy generator and photocatalyst in hydrogen production. Because of its hardness, rigidity and piezoelectric constant it is an important material in the ceramics industry, while its low toxicity, biocompatibility and biodegradability make it a material of interest for biomedicine and in pro-ecological systems. [4] The variety of structures of nanometric zinc oxide means that ZnO can be classified among new materials with potential applications in many fields of nanotechnology. Zinc oxide can occur in one- (1D), two- (2D), and three-dimensional (3D) structures. [5]
Figure 1. Examples of zinc oxide structure
In this review, the methods of synthesis, modification and application of zinc oxide will be discussed. The zinc oxide occurs in a very rich variety of structures and offers a wide range of properties. [6] The variety of methods for ZnO production, such as vapour deposition, precipitation in water solution, hydrothermal synthesis, the sol-gel process, precipitation from microemulsions and mechanochemical processes, makes it possible to obtain products with particles differing in shape, size and spatial structure. These methods are described in detail in the following sections. In this paper, we have extensively reviewed ideas behind the antibacterial activity of ZnO-NPs covering tech niques of evaluating bacteria viability. [7-8] In the subsequent sections, we have discussed the factors affecting the antibacterial activity, including UV illumination, ZnO particle size, concentration, morphology, surface modifications by annealing, surface defects, and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). A brief presentation of an experimental case study, carried by authors on antibacterial activity re sponse to E. coli, was explored. [9]
ZnO is described as a functional, strategic, promising, and versatile inorganic material with a broad range of appli cations. It is known as II–VI semiconductor, since Zn and O are classified into groups two and six in the periodic table, respectively. ZnO holds a unique optical, chemical sensing, semiconducting, electric conductivity, and piezo electric properties. It is characterized by a direct wide band gap (3.3 eV) in the near-UV spectrum, a high exci tonic binding energy (60 meV) at room temperature [19–23], and a natural n-type electrical conductivity. These characteristics enable ZnO to have remarkable ap plications in diverse fields. The wide band gap of ZnO has significant effect on its properties, such as the electrical conductivity and optical absorption. [10] The excitonic emis sion can persevere higher at room temperature and the conductivity increases when ZnO doped with other metals. Though ZnO shows light covalent character, it has very strong ionic bonding in the Zn–O. Its longer dura bility, higher selectivity, and heat resistance are preceded than organic and inorganic materials. The synthesis of nano-sized ZnO has led to the investigation of its use as new antibacterial agent. In addition to its unique antibac terial and antifungal properties, ZnO-NPs possess high catalytic and high photochemical activities. ZnO possesses high optical absorption in the UVA (315–400 nm) and UVB (280–315 nm) regions which is beneficial in antibacterial response and used as a UV protector in cosmetics. [11]
The nanostructured ZnO has been emerged as a potential candidate for applications in sensors, energy harvesting, and many electronic devices. Many pronounced applications are being currently explored in the biomedical and antiviral areas. This is as a result of their potential biocompatibility over other metal oxides, solubility in al kaline medium, and the Zn–O terminated polar surfaces. The unique properties and versatility of ZnO pave the way to use various methods to synthesize various ZnO nanostructures. ZnO-NPs can be synthesized through var ious methods by controlling the synthesis parameters. The properties can be tailored by shape and size, resulting in renewable applications relevant to their structural proper ties. [12] Mostly, the selected method depends on the desired application, as different methods produce different morphologies and also different sizes of ZnO particles. Ac cordingly, the chemical and physical parameters such as the solvent type, precursors, pH, and the temperature were highly considered. [13] An assortment of ZnO nanostructures with different growth morphologies such as nanorods, nanosphere, nanotubes, nanowires, nanoneedles and nanorings have been successfully synthesized. Such unique ZnO nanostructures reflected the richest nanocon figuration assembly compared to other nano-metal oxides, in terms of properties and structure, such as nanobelts, nanocages, nanocombs and nanosprings/nanohelixes. [14] Other shapes can also be obtained, such as ZnO spirals, drums, polyhedrons, disks, flowers, stars, boxes, and plates, those are possibly grown by adjusting the growth conditions. Each nanostructure has specific structural, op tical, electrical, and physicochemical properties, per mitting remarkable applications. These nanostructures have been fabricated using variety of physical and chemical techniques; however, the chemical techniques allow better control of the particle size and morphology. The most adopted fabrication methods include thermal evaporation of ZnO powders at 1400 C, hydrothermal synthesis, sol gel technique, simple thermal sublimation, self-combustion, polymerized complex method, vapor–liquid–solid technique, double-jet precipitation, and solution synthesis. The solution process was used by several re searchers to produce selective ZnO nanostructures. [15] They have synthesized flower-shaped ZnO nanostructures which were produced via solution process at low temperature (90 C) using the zinc acetate dihydrate and NaOH. These nanostructures plus others such as nanowires, nanoplates, and nanorods have been key factors for the antibacterial activity, as each morphology accounts for a certain mechanism of action. Thus, a large number of re searchers have been motivated to achieve selective nanostructured ZnO for the antibacterial tests. They succeeded to produce morphologies that were highly com patible with the antibacterial activity. The method yielded struc tures of spherical surface that showed high antibacterial activity against the tested pathogens. [16] Similarly, spherical shaped ZnO-NPs in another investigation were obtained via soft chemical solution process, and it was used for the treatment of bacteria (E. coli, S. aureus, P. aeruginosa, B. subtilis, and S. acidaminiphila) and cancer cells (HepG2 and MCF-7 cell lines). While have synthesized ZnO powder hydrothermally with the addition of different stabilizing agents leading to different nanostructures. The obtained synthesized ZnO has shown nanorods of hexagonal prismatic and hexagonal pyramid like structures, with some spherical and ellipsoid shapes. These different morphologies displayed pronounced an tibacterial effect toward the targeted bacteria. Further discussions of some synthesis methods and their corresponding mor phology of ZnO. Usually, antibacterial tests are done in aqueous media or cell culture media. ZnO is known as nearly insoluble in water, it agglomerates immediately with water during synthesis due to the high polarity of water leading to de position. [17-18] Issues of aggregation, re-precipitation, settling, or non-dissolution impede the synthesis processes. In this regard, a number of researchers considered this difficulty by using certain additives that have no significant effect in the antibacterial activity. As such, in the above-mentioned study [19], the addition of PVA, polyvinylpyrrolidone (PVP), and poly (a, c, L-glutamic acid) (PGA; see Abbre viations) as stabilizers enhanced ZnO morphology and size for the antibacterial activity. Meanwhile, Zhang et al. have addressed the problem by adding dispersants polyethylene glycol (PEG; see Abbreviations) and PVP (10 % of the amount of ZnO-NPs) which enhanced the stability of ZnO and resulted in ZnO nanofluids, well suited for the an tibacterial tests. While other researchers used appropriate capping agents or deflocculants (sodium silicate Na2 SiO3 or sodium carbonate Na2CO3). [20]
ZnO exhibits three crystallize structures namely, wurtzite, zinc-blende and an occasionally noticed rock-salt. The hexagonal wurtzite structure possesses lattice spacing a = 0.325 nm and c = 0.521 nm, the ratio c/a * 1.6 that is very close to the ideal value for hexagonal cell c/ a = 1.633. Each tetrahedral Zn atom is surrounded by four oxygen atoms and vice versa. The structure is ther modynamically stable in an ambient environment and usually illustrated schematically as a number of alternating planes of Zn and O ions stacked alongside the c-axis. Zinc blende structure is metastable and can be stabilized via growth techniques [21-22].
Nanoparticles Bacteria are generally characterized by a cell membrane, cell wall, and cytoplasm. The cell wall lies outside the cell membrane and is composed mostly of a homogeneous Rocksalt Membrane Nuclear materials Flagella peptidoglycan layer (which consists of amino acids and sugars). The cell wall maintains the osmotic pressure of the cytoplasm as well the characteristic cell shape. Gram positive bacteria have one cytoplasmic membrane with multilayer of peptidoglycan polymer, and a thicker cell wall (20–80 nm). Whereas gram-negative bacteria wall is composed of two cell membranes, an outer membrane and a plasma membrane with a thin layer of peptidoglycan with a thickness of 7–8 nm. NPs size within such ranges can readily pass through the peptidoglycan and hence are highly susceptible to damage. [23] The cytoplasm, a jelly-like fluid that fills a cell, involves all the cellular components except the nucleus. The functions of this or ganelle include growth, metabolism, and replication. [24] Consequently, the cytoplasm contains proteins, carbohydrates, nucleic acids, salts, ions, and water (*80 %). This composition contributes in the electrical conductivity of the cellular structure. The overall charge of bacterial cell walls is negative. Figure 1b shows typical bacteria cell structures. Antibacterial activity is known according to The American Heritage Medical Dictionary 2007, as the action by which bacterial growth is destroyed or inhibited. [25] It is also described as a function of the surface area in contact with the microorganisms. While antibacterial agents are selective concentration drugs capable to damage or inhibit bacterial growth and they are not harmful to the host. These compounds act as chemo-therapeutic agents for the treatment or prevention of bacterial infections. Zinc oxide (ZnO) is a highly promising antimicrobial material with broad-spectrum activity against bacteria, fungi, and viruses. Its antimicrobial action primarily involves reactive oxygen species generation, zinc ion release, membrane disruption, and intracellular toxicity. ZnO nanoparticles exhibit superior activity because of their nanoscale dimensions and increased surface area. [26]
Figure.2: Crystals of ZnO
Zinc oxide nanoparticles (ZnO-NPs) exhibit potent antibacterial activity through multiple mechanisms that collectively lead to bacterial cell death. [27] One of the primary mechanisms involves the generation of reactive oxygen species (ROS) such as hydroxyl radicals (•OH), superoxide anions (O2−), and hydrogen peroxide (H2O2). These reactive species induce oxidative stress, resulting in lipid peroxidation, protein denaturation, enzyme inactivation, and DNA damage within bacterial cells. [28] Additionally, ZnO-NPs release Zn2+ ions, which interfere with cellular metabolic processes and disrupt membrane integrity. Due to their nanoscale size and large surface area, ZnO-NPs can strongly interact with bacterial cell walls through electrostatic attraction, causing membrane permeability changes, leakage of intracellular contents, and eventual cell lysis. Furthermore, nanoparticles may penetrate inside bacterial cells and disturb intracellular organelles and biochemical pathways, ultimately inhibiting bacterial growth and survival. The combined effects of ROS generation, zinc ion release, and membrane disruption make ZnO-NPs highly effective against both Gram-positive and Gram-negative bacteria. [29]
Ultraviolet (UV) illumination significantly enhances the antimicrobial activity of ZnO nanoparticles due to their photocatalytic nature. When ZnO is exposed to UV light, electrons in the valence band become excited and move to the conduction band, leaving behind positively charged holes. These electron–hole pairs react with oxygen and water molecules present on the surface to generate reactive oxygen species (ROS) such as hydroxyl radicals, superoxide ions, and hydrogen peroxide. [30-31] These ROS attack microbial cell membranes, proteins, lipids, and nucleic acids, leading to oxidative stress and bacterial cell death. Therefore, ZnO exhibits stronger antibacterial efficiency under UV irradiation compared to dark conditions. [32]
The morphology or structural shape of ZnO nanoparticles plays a crucial role in determining their antimicrobial performance. ZnO can be synthesized in various forms such as nanorods, nanowires, nanospheres, nanoflowers, nanotubes, and nanoplates. [33] Different morphologies possess different surface areas, surface defects, and crystal orientations, which influence ROS generation and microbial interaction. Structures with higher surface area, such as nanoflowers and nanorods, provide greater contact with bacterial cells and improved photocatalytic activity, resulting in enhanced antimicrobial effects. Morphology also affects particle penetration into microbial membranes and the release of Zn2+ ions. [34-35]
Thermal annealing is a heat-treatment process used to improve the structural and surface properties of ZnO nanoparticles. Annealing enhances crystallinity, reduces structural defects, modifies particle size, and improves surface stability. These changes can significantly influence antimicrobial activity. [36-37] Proper annealing temperatures may increase photocatalytic efficiency and ROS production, thereby enhancing bacterial inhibition. Surface modification by thermal annealing also improves particle dispersion and reduces agglomeration, allowing better interaction between ZnO nanoparticles and microbial cells. However, excessive annealing temperatures may cause particle growth and reduced surface area, which can decrease antimicrobial efficiency. [38]
Particle size and concentration are among the most important factors affecting the antimicrobial activity of ZnO nanoparticles. Smaller nanoparticles exhibit stronger antibacterial effects because they possess larger surface area-to-volume ratios, higher surface reactivity, and greater ability to penetrate bacterial cell membranes. Nanoparticles with sizes below 50 nm generally show enhanced ROS generation and increased interaction with microorganisms. [39] In addition, antimicrobial activity increases with increasing ZnO concentration because a greater number of particles are available to interact with microbial cells and generate oxidative stress. However, excessively high concentrations may produce cytotoxic effects on normal mammalian cells, making dose optimization essential for biomedical applications [40].
Evidence has shown that enzymes, protein and other compounds produced by microbes play a vital role in the synthesis process. Nonetheless, to date, the data on the identification of chemical components responsible for the synthesis of NPs has been scant. Microbes exhibit the intrinsic potential to synthesise NPs of inorganic materials, which may be routed either by the intracellular or extracellular pathway. [41] Extracellular synthesis is more advantageous and has been widely applied compared to the intracellular route. This is mainly due to the fact that it could be used to synthesise large quantities and involves simple downstream processing that eliminates various steps of synthesis, easy separation and industrialization. [42] While the recovery process of NPs in the intracellular synthesis requires additional step such as harvesting the cell biomass by centrifugation and subjected to several cycle ultra-sonication for cells disruption to obtain the purified NPs. Nonetheless, the specific mechanism with regard to this has not been completely elucidated. [43]
Evidence has shown that heavy metal ions exhibit great threat to the microbes in which when there is a threat, the microbes will react by grip ping or trapping the ions on the cell wall through the electrostatic interactions [44]. This is due to the fact that metal ion is attracted to the negative charge from the carboxylate groups (specific enzymes, cysteine, polypep tides) that is present on the cell wall. Furthermore, the trapped ions are reduced into the elemental atom initiated by the electron transfer from NADH by NADH-dependent reductase that acts as an electron car rier, which is embedded in the plasma membrane. [45] Finally, the nuclei grow to form NPs and accumulate in the cytoplasm or in the cell wall (periplasmic space). On the other hand, the protein or peptides and amino acids such as cysteine, tyrosine and tryptophan exist inside the cells are responsible for providing stabilization of NPs. Intracellular mechanisms of microbial synthesis In the intracellular synthesis pathway, the cell walls of microbes and ions charge play an important role in the synthesis of NPs. [46] This involves distinctive ion transportation in the microbial cell in the presence of enzymes, coenzymes and others. The cell wall of microbes consists of a variety of polysaccharides and protein, which provides active sites for binding of the metal ions. Moreover, not all microbes are able to synthesize metal demonstrated the intracellular mechanisms using Verticillium sp. for the synthesis of NPs involving three steps, which are trapping, bioreduction and capping. The interaction forces between metal ions and the enzymes present on the cell wall reduce the metal ion within the cell wall leading to the aggregation of metal atoms and formation of metal NPs. The authors also reported the presence of metal NPs on the cytoplas mic membrane by transmission electron microscopy (TEM) analysis, which suggested that the formation of NPs occur in both the cell wall and the cytoplasm of the cell. [47]
Numerous studies reported that extracellular synthesis is a nitrate reductase-mediated synthesis, which is responsible for the reduction of metal ions into metal NPs. The extracellular synthesis pathway involves enzyme-mediated synthesis which located on the cell membrane or the releasing of the enzyme to the growth medium as an extracellular enzyme. Nitrate reductase is an enzyme in the nitrogen cycle that catalyses the con version of nitrate to nitrite. For instance, the bio reduction of Zn2+ was initiated by the electron transfer from NADH by NADH-dependent reductase that acts as an electron carrier. Consequently, the Zn2+ obtained electron and reduced to Zn0.[48] Subsequently, this resulted in the formation of ZnO NPs. Studies have shown that protein produced and se creted by microbes play an important role in the NPs synthesis. Nevertheless, some studies sug gested that the native form of the protein is not compul sory for the NPs synthesis process. [49] A study revealed that amino acids present in the protein were found to interact with the Zn2+ ions to form NPs. The study also investigated the ability of denatured (heat treated) and native (untreated) protein present in the fungal cell-free filtrate suspension for the synthesis of ZnO NPs. The results demonstrated that both heats treated and untreated samples were able to synthesize ZnO NPs. Notably, the absorbance spectra result by UV Vis demonstrated a higher reaction rate on the heat treated protein compared to the untreated. This indi cates that the synthesis of ZnO NPs was higher in the heat-treated samples. Hence, the results confirmed that the presence of the native form of the protein is not mandatory for the synthesis process. This may attribute to the fact that, the interaction between hydrogen bond and non-polar hydrophobic was disrupted during the heating process. [50] Consequently, this resulted in the exposed contact of amino acids with zinc ions that led to the formation of ZnO NPs. Moreover, the authors also suggested that the biosynthesis of metal NPs was non-enzymatic due to the denaturation of the structure of the enzyme during heat treatment. In some cases, the non-enzymatic mediated synthesis depends on the certain organic functional groups present on the microbial cell wall, which facilitates the reduction of metal ions. The live cell biomass and dead cell (heat killed by autoclaving) of Corynebacterium glutamicum were used to synthesize silver NPs. After sonication of the cell, the UV-Vis spectra results demonstrated a strong plasmon resonance between 400 and 450nm for both samples. Both samples were further incubated for a few days. The results indicated that the peak area and height of the UV-Vis spectrum for the dead cell were comparatively higher compared to live cell samples. This indicates a higher productivity of silver NPs. [51]
The antibacterial activity of zinc oxide nanoparticles (ZnO-NPs) is attributed to several interconnected mechanisms that collectively inhibit bacterial growth and induce cell death. One of the most widely accepted mechanisms is the generation of reactive oxygen species (ROS), including hydroxyl radicals (•OH), superoxide anions (O2−), and hydrogen peroxide (H2O2). These reactive molecules cause oxidative stress that damages bacterial proteins, lipids, enzymes, and nucleic acids. [52] Another important mechanism involves the release of Zn2+ ions from the nanoparticle surface, which interfere with metabolic pathways, enzyme systems, and membrane transport processes within bacterial cells. ZnO-NPs also interact directly with the bacterial cell membrane through electrostatic attraction, leading to membrane disruption, increased permeability, leakage of intracellular components, and eventual cell lysis. Due to their nanoscale dimensions, the particles may penetrate into bacterial cells and disturb intracellular structures, ribosomes, and DNA replication processes. Additionally, ZnO nanoparticles can inhibit biofilm formation and impair bacterial adhesion, further reducing microbial survival. The synergistic action of ROS generation, zinc ion release, membrane damage, and intracellular interference makes ZnO-NPs effective antimicrobial agents against both Gram-positive and Gram-negative bacteria. [53]
Some plants in Indonesia have a high potential as a raw material in the manufacture of herbal cosmetics:
1. Jamblang
Jamblang (Syzygium cumini), commonly known as Java plum or black plum, is a medicinal plant rich in natural antioxidants such as flavonoids, anthocyanins, tannins, phenolic acids, and vitamin C. The fruit, seeds, leaves, and bark possess strong free radical scavenging activity. Anthocyanins present in the dark purple fruit help neutralize reactive oxygen species (ROS) and reduce oxidative stress. Jamblang extracts have shown significant antioxidant potential in DPPH, FRAP, and ABTS assays. Due to these properties, the plant is widely investigated for protective effects against diabetes, inflammation, cardiovascular disorders, and aging-related diseases. [54]
2. Tomato
Tomato (Solanum lycopersicum) is an important dietary source of antioxidants including lycopene, β-carotene, vitamin C, vitamin E, and polyphenols. Lycopene is the major carotenoid responsible for the red color of tomatoes and is considered a highly potent antioxidant capable of quenching singlet oxygen and preventing oxidative cellular damage. Regular consumption of tomatoes is associated with reduced risk of cancer, cardiovascular diseases, and skin aging. Heat processing of tomatoes may increase the bioavailability of lycopene, enhancing antioxidant effectiveness. [55]
3. Dayak onion
Dayak onion (Eleutherine palmifolia), also known as red bulb onion, is a traditional medicinal plant widely used in Southeast Asia. It contains bioactive compounds such as flavonoids, alkaloids, phenolics, tannins, and naphthoquinones that contribute to strong antioxidant activity. Extracts of Dayak onion effectively scavenge free radicals and inhibit lipid peroxidation. Studies suggest that its antioxidant properties may help protect against oxidative stress-related disorders including diabetes, hypertension, inflammation, and cancer. The bulb extract is especially valued in herbal medicine because of its high phenolic content. [56]
4. Karsen
Karsen (Muntingia calabura), commonly known as Jamaican cherry or Panama berry, possesses significant antioxidant potential due to the presence of flavonoids, phenolic compounds, tannins, and vitamin C. The leaves and fruits exhibit strong free radical scavenging activity and reducing power. Antioxidant compounds in Karsen help minimize oxidative damage to cells and tissues, thereby supporting anti-inflammatory, antimicrobial, and anticancer activities. The plant has gained attention in phytopharmaceutical research for its ability to protect biological systems from oxidative stress-induced damage. [57]
Kemuning leaves (Murraya paniculata) are widely used in traditional herbal skincare preparations because of their antioxidant, anti-inflammatory, and antimicrobial properties. The leaves contain flavonoids, alkaloids, coumarins, and essential oils that help protect the skin from oxidative stress and microbial infections. Kemuning leaf extracts may help reduce acne, soothe skin irritation, improve skin texture, and promote wound healing. Due to their natural antibacterial activity, the leaves are also incorporated into herbal facial cleansers and topical formulations for oily and acne-prone skin. [58]
Kunyit or turmeric (Curcuma longa) is one of the most important herbal ingredients used in skincare because of its active compound curcumin. Curcumin possesses strong antioxidant, anti-inflammatory, antimicrobial, and skin-brightening properties. Turmeric helps reduce acne, pigmentation, redness, and skin inflammation while promoting wound healing and collagen production. It also protects the skin against oxidative damage caused by UV radiation and environmental pollutants. Turmeric is commonly used in face masks, creams, soaps, and anti-aging cosmetic products. [59]
Cananga flowers (Cananga odorata), commonly known as ylang-ylang flowers, are valued in skincare and aromatherapy because of their soothing, moisturizing, and antimicrobial effects. The flowers contain essential oils rich in linalool, germacrene, and benzyl acetate, which help maintain skin hydration and reduce irritation. Cananga flower extracts and essential oils are frequently used in perfumes, lotions, massage oils, and cosmetic formulations for calming sensitive skin and improving skin softness. Their antimicrobial activity may also assist in controlling minor skin infections and acne-causing microorganisms. [60]
Olive oil (Olea europaea L.): Olive oil consists of a mixture of triglycerides of oleic acid ester, palmitic acid and other fatty acids, such as squalene (up to 0, 7 %) and sterols (about 0.2% phytosterol and tocopherol). Olive oil acts as hair moisturizer hair and skin irritation reducer. In addition, vitamin E in olive oil protects a hair loss. [61] Thus, olive oil is good to be used in cosmetic hair preparations such as gel and liquid hairtonic. Coconut (Cocos nucifera): Coconut is an important member of the Arecaceae (palm) family. Coconut is a large palm, growing up to 30 m, and usually used for cooking. Coconut oil has a good saponification value that can be used as shampoo for hair treatment. Celery (Apium graveolens): The main content of celery is butylphthalide known as the main aroma of celery. There are also a number of flavonoids such as graveobiosid A (1-2%) and B (0, 1 0.7%) as well as fatty acids and phenol group compounds. The main content of fatty acids acid petroselin (40-60%). In addition, the leaves and stems contain steroids as stigmasterol and sitosterol. Celery is also known to have tremendous benefits inhair care because of of nutrient contents in celery such as vitamin A, vitamin B, sodium, iron and calcium. Kemiri (Aleurites moluccanus): Kemiri seeds are used as a source of oil and spices. It has many mineral deposits such as phosphorus, calcium, potassium, magnesium, and other minerals for stimulating healthy hair, overcoming hair loss and dullness. [62] In Tonga, until now, the mature kemiri (named after “tuitui”) is used as a paste, soap and shampoo. Skin whitening Akar manis (Glycyrrhiza glabra): Akar manis extract is rich in natural antioxidants. The main antioxidant compound in Glycyrrhiza glabra extract is glycyrrhizin (glycyrrhizic acid) and flavonoid. The role of plant extracts on the skin is primarily associated with antioxidant, skin rejuvenation, skin lightening and photoprotection.[63] Previous research showed that a cream formula of plant extracts Glycyrrhiza glabra was chemically and physically stable during storage conditions and without induction of allergic or contact dermatitis. Bengkuang (Pachyrhizus erosus): Bengkuang has benefits to maintain healthier skin and remove dead skin cells. Bengkuang contains Vitamin C which can nourish the skin and can be used as a base material for the preparation of masks to refresh the face and brighten the skin. Temulawak (Curcuma xanthorrhiza): Temulawak is a Zingiberaceae species that is empirically widely used as a traditional medicine especially its rhizome. Anti-acne agents and skin bleaches are an interesting subject on natural skin care of Temulawak because of its vitamin C content. Temulawak is often used as a base ingredient in cosmetic skin lightening preparations in the facial mask, lotion and face cream. [64]
Microbes-mediated synthesis of NPs has the potential to be a great alternative to chemical and physical methods, despite the main drawback in applying biological synthe sis of NPs, which refers to the difficulty in controlling both the size and the shape of NPs.[65] The main major concerns in using microbes are to increase yield production for industrial scale, which demand further investigation. It has been widely reckoned that the physicochemical properties of NPs are highly dependent on their size and morphology structures. Studies have proven the direct effects of NPs size and shape on their performance. Sadeghi et al., [66] revealed that the nano plate-shaped NPs exhibited good antibacterial activity due to their large surface area, in comparison to those with nano-rod shape. In another study, ZnO NPs at 12nm ef fectively inhibited the growth of pathogenic bacteria, when compared to those at 212nm [67]. Therefore, in order to generate effective size distribution, morphologies, and yield production of NPs, it is necessary to optimize both the cultural condition and the varied physical parameters, including pH, temperature, metal ions concentration, microbial age, and reaction time. [68] The biological synthesis of NPs seems to gain better commercial acceptance if the NPs are produced in high yield with the desired size and shape. The schematic representation of parameters for producing the desired NPs [69].
Generally, pH is a key factor that has a major role in the synthesis of metal NPs, mainly because pH has the abil ity to alter the shape of biomolecules that is responsible in capping and stabilizing the NPs [70]. Assessed the biosynthesis of gold NPs using Verticillium luteoalbum by varying the pH level to deter mine its impact on the size and shape of the generated NPs. The outcomes displayed a majority smaller size of NPs with spherical shape obtained at pH3, in comparison to those retrieved for pH values 7 and 9 that predominantly produced larger NPs with irregular and undefined shapes. [71] Optimization of pH may also be influenced by the species of microbes applied in the synthesis. For instance, an acidophilic bacterium, Lactobacillus casei, resulted in increased absorbance of silver NPs production as the pH value was reduced; indicating that growth and enzymes activity of L. casei are better in weak acidic environment [72]. In the case of alkaline condition, asserted that hydroxide ion is essential to decrease metal ions. The authors observed rapid increment in silver conversion within less than 30min’ reaction time at pH 10; signifying that the protein, which served as a reducing agent, was present in the supernatant and was active in re ducing power under alkaline conditions. [73] Additionally, the authors confirmed their results by observing the NPs with TEM analysis that recorded smaller size of NPs ranging between 10 and 15nm. [74]
Numerous researches have investigated the impacts of various temperatures on the size and yield production of NPs. The effects of temperatures on NPs size produced by Trichoderma viride at 10°C, 27°C, and 40°C.[75] The UV-Vis spectra outcomes showed that lower wavelength regions at 405 nm were obtained at 40°C and higher wavelength re gions at 420nm and 451nm were obtained at 27°C and 10°C, respectively, indicating increment in NPs size at higher wavelength regions.[76] The author also verified their results with TEM analysis that showed a high temperature of 40°C generated smaller monodisperse NPs size ranging between 2 and 4nm, while at a lower temperature, larger NPs were produced. In another study, maximum produc tion of silver NPs synthesized by Sclerotinia sclerotiorum was obtained at 80°C with 10–15nm size range. This pos tulated that higher temperature increased the kinetic en ergy, thus leading to rapid synthesis rate and maximum NPs with a smaller size [77]. The decrease in particle size with increased temperature is normally due to increment in reaction rate at higher temperature. This causes the metal ion to be consumed rapidly in forming nuclei, while the size is reduced initially due to reduction in the aggre gation of the growing NPs. [78]
The impact of various precursor salt concentrations on the synthesis of metal NPs using soil fungus Cladosporium oxysporum revealed that the optimum concentration of precursor salt at 1.0 × 10−3mol/L gave maximum NPs yield.[79] Nonetheless, at concentrations 2.0 × 10−3 and 5.0 × 10−3mol/L, no NPs was generated due to the in sufficient biomolecules in minimizing the high amount of metal ions present [80]. This finding is in agreement with that reported absorbance of ZnO NPs by UV-Vis spectra in creased with increment of precursor concentration (2.5 × 10−5 to 1.0×10−4mol/L). They added that further increment in concentration (2.0 × 10−4mol/L) resulted in broad peak, while decrease in absorbance signified re duction in the synthesis of ZnO NPs.[81] The influence of metal ion concentration on the synthesis of silver NPs using Penicillium aculeatum Su1 suggested that high concentration of metal ions increased the aggregation of NPs, which resulted in the formation of larger NPs size. The authors reported that maximum production of NPs yield was obtained at absorbance peak of 415nm by UV vis spectra, whereby as the concentration increased to 2.5 × 10−3mol/L, the absorbance peak shifted to 435nm; signifying the increased size of NPs formation [82].
CONCLUSION:
Zinc oxide is a multifunctional material because of its many interesting properties (piezo- and pyroelectric), a wide range of UV absorption, and high photostability, biocompatibility and biodegradability. ZnO can also be obtained with a variety of particle structures, which determine its use in new materials and potential applications in a wide range of fields of technology. Therefore the development of a method of synthesizing crystalline zinc oxide which can be used on an industrial scale has become a subject of growing interest in science as well as industry. As can be seen from the survey of recent literature presented here, particles of zinc oxide—both nano- and micrometric—can be produced by many different methods. These can be divided into metallurgical and chemical methods. In metallurgical processes, zinc oxide is obtained by the roasting of a suitable zinc ore, via a direct or indirect process. Chemical methods can be divided into two groups: dispersion methods and condensation methods. In dispersion (mechanochemical) processes, zinc oxide is obtained by the grinding of suitable precursors. The resulting product may contain particles measuring approximately 20 nm. There are many native herbal plants such as dayak onion bulb, kemuning leaf, kecombrang, red betel, kemiri, akarmanis, etc. which can be formulated into various categories of cosmetic preparations such as antioxidants, anti-aging, lip color, liquid bath soap, hair and skin care in accordance with their contents of phytochemicals substances. Thus, cosmetics industryin Indonesia has a great opportunity to become one of the largest herbal cosmetics industries in the world. Technology and knowledge relating to oxide materials of nano- and micrometric dimensions are currently among the most rapidly developing scientific and technological disciplines. The use of such materials can provide, among other things, more durable ceramics, transparent solar filters blocking infrared and ultraviolet radiation, and catalysts. These materials are also useful in biomedical research and in the diagnosis and treatment of diseases. They can be used to deliver medicines directly to diseased cells, in a way that avoids adverse effects. The survey of the literature that has been given here shows that zinc oxide can be classed as a multifunctional material. This is thanks to such properties as high chemical stability, low electrical constant, high electrochemical coupling index, wide range of radiation absorption, and high photostability. It can be expected that interest in zinc oxide will continue to grow, and that this will lead to the development of new possibilities for its application.
REFERENCES
Pratibha Yadav, Ranvijay Singh*, Sanjay Kumar Kushwaha Chemically Synthesized Zinc Oxide in Peel-Off Facial Masks: Formulation Strategies, Characterization, and Antimicrobial Potential & Applications, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 5, 4622-4639. https://doi.org/10.5281/zenodo.20278179
10.5281/zenodo.20278179