
==== Front
Heliyon
Heliyon
Heliyon
2405-8440
Elsevier

S2405-8440(24)13163-5
10.1016/j.heliyon.2024.e37132
e37132
Review Article
Advancements in the nanodelivery of azole-based fungicides to control oil palm pathogenic fungi
Asmawi Azren Aida ab
Adam Fatmawati fatmawati@umpsa.edu.my
a⁎
Mohd Azman Nurul Aini ainiazman@umpsa.edu.my
a⁎⁎
Abdul Rahman Mohd Basyaruddin cd
a Faculty of Chemical and Process Engineering Technology, Universiti Malaysia Pahang Al-Sultan Abdullah, Gambang, 26300, Pahang, Malaysia
b Faculty of Pharmacy and Biomedical Sciences, MAHSA University, Bandar Saujana Putra, Jenjarom, 42610, Selangor, Malaysia
c Foundry of Reticular Materials for Sustainability, Institute of Nanoscience and Nanotechnology, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia
d Integrated Chemical BioPhysics Research, Faculty of Science, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia
⁎ Corresponding author. Faculty of Chemical and Process Engineering Technology, Universiti Malaysia Pahang Al-Sultan Abdullah, Gambang, 26300, Pahang, Malaysia. fatmawati@umpsa.edu.my
⁎⁎ Corresponding author. ainiazman@umpsa.edu.my
29 8 2024
30 9 2024
29 8 2024
10 18 e3713218 1 2024
26 8 2024
28 8 2024
© 2024 The Authors. Published by Elsevier Ltd.
2024

https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).
The cultivation of oil palms is of great importance in the global agricultural industry due to its role as a primary source of vegetable oil with a wide range of applications. However, the sustainability of this industry is threatened by the presence of pathogenic fungi, particularly Ganoderma spp., which cause detrimental oil palm disease known as basal stem rot (BSR). This unfavorable condition eventually leads to significant productivity losses in the harvest, with reported yield reductions of 50–80 % in severely affected plantations. Azole-based fungicides offer potential solutions to control BSR, but their efficacy is hampered by limited solubility, penetration, distribution, and bioavailability. Recent advances in nanotechnology have paved the way for the development of nanosized delivery systems. These systems enable effective fungicide delivery to target pathogens and enhance the bioavailability of azole fungicides while minimising environmental and human health risks. In field trials, the application of azole-based nanofungicides resulted in up to 75 % reduction in disease incidence compared to conventional fungicide treatments. These innovations offer opportunities for the development of sustainable agricultural practices. This review highlights the importance of oil palm cultivation concerning the ongoing challenges posed by pathogenic fungi and examines the potential of azole-based fungicides for disease control. It also reviews recent advances in nanotechnology for fungicide delivery, explores the mechanisms behind these nanodelivery systems, and emphasises the opportunities and challenges associated with azole-based nanofungicides. Hence, this review provides valuable insights for future nanofungicide development in effective oil palm disease control.

Keywords

Oil palm
Azoles
Fungicides
Nanodelivery
Pathogenic fungi
Ganoderma
==== Body
pmc1 Introduction

The oil palm is a tropical plant that contributes significantly to the global economic and agricultural sector by providing edible oils, fats, and a variety of essential byproducts. Palm oil currently leads the global vegetable oil market, accounting for around 35.7 % of total consumption, surpassing soybean, rapeseed, and sunflower oils [1]. Global palm oil consumption is projected to intensify, driven by increasing global demand for vegetable oils, particularly in the biofuel and food industries [2,3]. The largest share of palm oil production, around 83 %, comes from Malaysia and Indonesia, collectively earning approximately USD 29.17 billion and USD 29.66 billion in export revenue from palm oil and its related products [1,4]. However, the sustainability and productivity of this crop are under constant threat from a range of pathogenic fungi. Basal stem rot (BSR), attributed to Ganoderma boninense, represents a profoundly detrimental fungal disease in major oil palm-producing countries [[5], [6], [7]]. BSR has substantially reduced oil palm density per hectare and fresh fruit bunch productivity, resulting in significant yield losses of up to 80 % [6,8,9]. Consequently, BSR poses considerable economic challenges to oil palm cultivation, and the high persistent and widespread presence of G. boninense in the soil poses difficulties in effectively managing the disease.

Conventional control measures for pathogenic fungi rely heavily on the application of chemical fungicides. Among the fungicide classes, azole-based fungicides have been widely used for fungal infections in humans and plants since the 1970s [6,10]. They are prevalent in agriculture due to their broad-spectrum systemic mode of action, inexpensive and able to remain chemically stable, allowing them to endure in the environment for extended durations [[10], [11], [12]]. Azoles, specifically 14-demethylase inhibitors, have been shown to be effective against fungal diseases by inhibiting the ergosterol production pathway, which is a critical component of their cell membrane [13,14]. However, azole use in agriculture is highly debated due to concerns about endocrine disruption, environmental persistence, fungicide resistance, and potential health effects [[15], [16], [17]]. Furthermore, strict regulatory control has decreased the number of novel fungicides being discovered and registered, owing to the high cost and complexity of the procedure. As a result, these challenges have received increased worldwide attention, necessitating the development of alternative, efficient and sustainable control measures. In the wake of these challenges, the utilisation of nanotechnology has emerged as a viable and promising strategy for the effective delivery of agrochemicals, particularly azole-based fungicides.

Nanocarrier systems with unique properties and controllable size, offer a novel platform to enhance the efficacy and delivery of these fungicides. Through targeted delivery, increased penetration, and sustained release, nanodelivery not only addresses the shortcomings of conventional applications but also potentiates to mitigate fungal resistance development [17,18]. While significant progress has been made in exploring the potential uses of nanotechnology in agriculture over the past few decades, research on the role of nanocarriers in fungicide delivery remains limited. Besides, numerous challenges must be resolved in the near future before this technology can make meaningful contributions, notably in oil palm cultivation. Hence, it is crucial to continue research and development in this field in order to overcome the problems and turn nanotechnology into a sustainable and effective strategy. This aligns with the United Nations Sustainable Development Goals (UNSDGs), particularly Goal 2 (Zero Hunger) and Goal 12 (Responsible Consumption and Production). Additionally, nanotechnology in fungicide delivery supports Goal 3 (Good 10.13039/100018696 Health and Well-being) by reducing health risks associated with conventional fungicides and Goal 13 (Climate Action) by minimising environmental impact and promoting resilient agricultural systems. Herein, this review highlights advancements in the nanodelivery of azole-based fungicides and their sustainable application.

2 Oil Palm's Significance Amidst pathogenic fungal challenges

2.1 The importance of the oil palm industry

Elaeis guineensis is an oil palm variety indigenous to the West African tropical rainforests. It is distinguished by its monoecious nature, in which female and male reproductive organs coexist on the same tree. This leads to an allogamy or cross-pollination, where both genetic and external variables affect the "sex ratio" of the oil palm population [19,20]. The height of these palm trees can exceed 30 m, and they start bearing fruit bunches within three years after being planted. Their average lifespan is from 25 to 30 years, and each tree has the capacity to yield around 8 to 12 fruit bunches annually [21]. Palm oil is widely recognised as the oldest and most functional vegetable oilseed globally, primarily due to its remarkable potential for oil production. In comparison to other primary oilseed sources like sunflower, soybeans, and canola, a single hectare of oil palm plantation can yield oil quantities that are ten times higher [22,23]. This efficiency reduces the amount of land required to meet the oil demand. Besides, oil palm stands out in its dual oil production, which benefits various industries. Palm kernel oil is extracted from the seed or kernel, whilst palm oil is derived from the fruit's mesocarp or flesh, accounting for around 11 % and 89 % of the overall fruit oil production. Over three billion people consume palm oil daily, and it is a key ingredient in food preparation, particularly in Asia and Africa [23].

Projections from diverse industry reports indicate that the demand for palm oil could increase up to 156 million tonnes by the year 2050 [23,24]. The consistent rise in global demand has prompted numerous tropical countries to opt for oil palm cultivation as a means to bolster their economies [9,25]. Palm oil is currently grown predominantly in Asia, Africa and Latin America, with Malaysia and Indonesia having the highest certified area of planted oil palms by the Roundtable on Sustainable Palm Oil (RSPO) [26]. Notably, there was a significant increase in oil palm plantation expansion in this region from 2001 to 2016, with Malaysia and Indonesia experiencing 2.5-fold and 4.2-fold increases, respectively [27]. Furthermore, the oil palm industry is expanding in tropical Africa, with Côte d'Ivoire, Nigeria, Ghana, Cameroon, Angola, the Democratic Republic of Congo, Sierra Leone and Benin among the most prominent producers. Nonetheless, African oil palm crops are primarily used for domestic consumption, with only the Ivory Coast and Cameroon serving as major palm oil exporters [23]. In the Americas, oil palm plantations were initially introduced in Costa Rica and Honduras, followed by the subsequent emergence of the primary oil palm producers in Ecuador, Colombia and Guatemala [23,28]. However, this expansion has posed risks to deforestation, loss of biodiversity, and greenhouse gas emissions. In order to meet the projected demand for palm oil without significantly expanding land usage, it is crucial to achieve a significant improvement in crop productivity.

Despite the imperative to carefully assess the environmental effects of expanding oil palm cultivation, numerous initiatives are underway to promote sustainable palm oil production on a global scale. The RSPO is the preeminent non-profit organisation responsible for regulating sustainable palm oil [9,23]. Palm oil produced to RSPO standards is required to be deforestation-free. For instance, efforts are being made to convert only land currently utilised for pasture or unauthorised cultivation, and strategies are being implemented to enhance crop yields, thus minimising the need for additional land [29]. This will be crucial due to the limited availability of land in Malaysia and Indonesia. Malaysia's government has taken measures to curb further expansion of cultivated areas by preserving some of their forest regions [30]. Furthermore, crop growth has been declining since 2009, partly due to the oil palm's susceptibility to several diseases. The most severe incidences of these diseases are linked to pathogenic fungi and are especially common in replanted regions [9,23]. Implementing disease management measures can effectively curtail the undesired expansion of plantings by enhancing through mitigating disease infection in existing plantings. However, until now, most control strategies have only been able to extend the productive lifespan of infected palm trees without eradicating the diseases. As a result, discovering more efficient disease control strategies remains a crucial part of sustainable palm oil production.

2.2 Critical pathogenic fungi affecting oil palm

Critical pathogenic fungi have emerged as a significant cause of concern in the global palm oil industry, posing a threat to the health and productivity of oil palm plantations [5,31]. There is a range of diseases affecting oil palm plantations attributed to these harmful fungi, including basal stem rot (BSR), upper stem rot (USR) vascular wilt, brunch rot, sooty mold, and grey leaf blight. The impact of these diseases on oil palm cultivation varies according to the symptoms observed and the geographic regions where the crops are cultivated (Table 1). Ganoderma spp. stands out as the most destructive pathogen for oil palms, responsible for both BSR and USR infections. These infections are prevalent across Southeast Asia and particularly pronounced in replanted regions [6,21,32]. Additionally, Fusarium spp., particularly F. oxysporum, poses a significant threat by causing vascular wilt, which stands as the most devastating disease for oil palm cultivation in Africa and South America, resulting in severe losses in affected regions [33,34]. Various fungal infections, such as Ustulina deusta, Marasmius palmivorus, Meliola elaeidis, Pestalotiopsis palmarum and Curvularia eragrostidis, have been isolated from oil palm roots and leaves [[35], [36], [37], [38], [39]]. Lesions caused by these pathogenic fungi are frequently observed in oil palm cultivations, contributing to the complexity of disease control.Table 1 Overview of global palm oil diseases caused by pathogenic fungi.

Table 1Oil Palm Disease	Pathogen	Typical Damage/Symptoms	Current Distribution	Ref.	
Basal stem rot (BSR)	Ganoderma spp.	Damage to internal basal stem, yellowing and wilting of leaves and frond collapse, crown loss, reduced fruit production, root decay and palm death or collapse	Indonesia, Malaysia,
Thailand, Papua New Guinea, Nigeria, Colombia Cameroon, Solomon Island	[4,6,7,40]	
Upper stem rot (USR)	Ganoderma spp.	Infect and damage the upper region of the stem, yellowing and wilting of leaves and frond collapse, and palm death or collapse	Malaysia, Indonesia, Thailand, Papua New Guinea, Nigeria	[7,40,41]	
Vascular wilt	Fusarium oxysporum	Leaf yellowing, leaf drooping and wilting, vascular browning, reduced yield, and stunted growth	Nigeria, Ghana, Cameroon, Ivory coast,	[7,23,33]	
Charcoal rot	Ustulina deusta	Black rot at the base, leaves chlorotic, frond drooping and wilt, reduced fruit production and premature death of palms	Indonesia, Malaysia, Thailand	[36,42]	
Brunch rot	Marasmius palmivorus	Soft and mushy brunch tissue, foul odour, formation of fungal spores and mycelium on the surface of the fruits, premature fruit drop and reduced yield	Malaysia, Indonesia, Taiwan	[35,43]	
Sooty mold	Meliola elaeidis,
Brooksia tropicalis, Ceramothyrium spp., Capnodium spp.	The presence of a black, powdery coating on the surface of leaves and fronds and cause stunted growth if the coverage is extensive	Africa, Malaysia, Thailand, India	[36,44]	
Leaf blight/Leaf spot	Pestalotiopsis palmarum,
Curvularia spp., Helminthosporium spp., Cylindrocladium macrospores	Circular or irregular spots, yellowing of surrounding tissue, leaf wilting or drooping and premature leaf drop	Colombia,
Honduras, Venezuela, Peru, China, Ghana, Malaysia, Indonesia, Thailand	[36,40,45]	

Controlling the disease poses a significant challenge due to the persistent and soil-bound nature of the pathogen, particularly in the case of Ganoderma spp. This parasitic organism thrives by obtaining nutrients from tree stumps and roots. One significant challenge in dealing with Ganoderma infections is the difficulty in detecting early symptoms. Symptoms often manifest when the infection has progressed to an advanced stage, typically ranging from 60 % to 70 % [4]. Immature oil palms, once infected, usually succumb to the infection within a relatively short span of 1–24 months. In contrast, mature palms may persist for one to two years after the initial symptoms manifest [6,46]. The research findings indicate that out of all the Ganoderma spp. only G. boninense, G. miniatocinctum and G. zonatum were identified as pathogenic to oil palm. In contrast, G. tornatum, G. applanatum, G. pfeifferi, G. lucidum and G. philippi were shown to be non-pathogenic [47,48]. G. boninense is known to be the causal pathogen of BSR and USR, which are the most destructive diseases of oil palm in Southeast Asia [7,15,49]. More than 40 %–80 % of potential yield was lost as these diseases reduced fresh fruit bunch (FFB) and killed 80 % of palms in the middle of their economic life [21,23,50]. This resulted in an estimated potential yield loss of over 400,000 ha of matured oil palm [6,40,51]. G. boninense employs multiple pathways for host plant transmission, including basidiospore dispersion, the presence of secondary inoculum in the soil and root-to-root contact [4,6,8].

Ganoderma spp. have five stages in their life cycle: spores, spore germination, mycelium, primordia, and basidiocarp or fruiting body. As illustrated in Fig. 1, the fungus reproduces via spores and mycelia, with environmental variables such as wind and insects assisting in spore dissemination to other healthy oil palms [52,53]. Under favourable conditions, Ganoderma spores can successfully germinate, giving rise to primary hyphae, which eventually develop into primordia with more prolonged and denser mycelial structures. The pathogen's mycelium then infiltrates the tree's vascular system, producing enzymes that break down lignin, cellulose, and polysaccharides within the plant cell walls. This disruption significantly impairs the flow of nutrients and water, leading to a progressive deterioration in the tree's overall health [54,55]. Over time, these debilitating effects manifest in various symptoms, including the presence of basidiocarps resembling a fan or hoof on the surface of tree trunks on the stem, mottling of the lower fronds, growth retardation, water stress, a pale leaf canopy, and unopened spear leaves [6]. By this point, cultural measures frequently failed because more than half of the internal tissues were rotten after the disease symptoms appeared [56]. If left unaddressed, this relentless assault by Ganoderma ultimately ends in the collapse of the oil palm [6,40].Fig. 1 Ganoderma spp. life cycle. The fruiting bodies of Ganoderma spp. produce millions of basidiospores, which can be dispersed by wind, insects, or through root-to-root contact. The germinating basidiospores form mycelia and mate with compatible partners to form pathogenic dikaryotic mycelia. Subsequently, these mycelia progress to form primordia and colonise the oil palm's root and basal stem, eventually leading to the growth of basidiocarps on the affected tree's lower trunk. Figure created with BioRender.com.

Fig. 1

2.3 Current strategies in Ganoderma basal stem rot (BSR) disease control

The current approaches to managing Ganoderma spp. in oil palm plantations encompass cultural practices, chemical and biological techniques. Cultural practices employed in the Ganoderma BSR disease management involve a range of physical techniques aimed at creating an environment that is less conducive to the growth and spread of the pathogen. These approaches include surgery, soil mounding, trenching, clean clearing, and windrowing [6,57]. Soil mounding treatment can be effective in prolonging the productivity of infected palms, but it may not be effective in mitigating the BSR disease [4,6,58]. It involves removing any infected tissue through surgery and constructing elevated soil beds or mounds, typically with a diameter of around 1 m and a height of up to 0.75 m, around the tree base [59]. This method enhances soil drainage and aeration, making it less favourable to Ganoderma growth and preventing the weakened bole from being collapsed [21]. Besides, this approach can effectively extend the infected palm's lifespan, with a mortality rate of up to 4.45 % [57]. Moreover, excavating trenches with dimensions of 4 x 4 × 0.75 m around the infected palms had been recommended to mitigate the risk of infection through infected soil and root contact with nearby healthy palm trees by creating a barrier around the tree's roots [41,60]. However, the efficacy of trenches has been compromised due to either inadequate maintenance or insufficient depths, resulting in roots being able to cross underneath [60].

In addition, clean clearing and windrowing are two sanitation practices employed to reduce the dissemination of Ganoderma inoculum in oil palm cultivations. The process of clean clearing entails the elimination of infected palms, whereas windrowing involves chipping, pulverising, and stacking infected palms in windrows between planting, but at a considerable cost [4,7]. Open burning, traditionally employed for land-clearing activities in oil palm plantations by burning agricultural residue, infected palms, and undergrowth was a quick method for pest and disease control and soil enrichment. However, its detrimental effects on the environment, biodiversity, public health, and air quality led to significant regulatory changes over the past two decades. Countries began implementing laws to restrict or ban the practice, supported by the 10.13039/501100016268 Association of Southeast Asian Nations (10.13039/501100016268 ASEAN ) Agreement on Transboundary Haze Pollution in 2002, ratified by all 10.13039/501100016268 ASEAN countries. Similarly, European Union regulation 1306/2013 banned the practice across all EU countries, with many other regions following suit, opting instead for natural decomposition techniques [49,57,61]. Nevertheless, these practices may be less effective due to the persistence of residual spores or mycelia, hence continue to pose a risk to any nearby healthy palm trees. According to a study conducted by Virdiana et al. [62], it has been demonstrated that in the absence of chemical treatment and fallowing prior to windrowing, a significant proportion of oil palms, up to 41 %, remain susceptible to pathogen infection within the first seven years after planting. Therefore, using these measures does not successfully impede the proliferation of Ganoderma spp., thus necessitating exploring other disease management options.

Biocontrol measures, specifically the use of Trichoderma spp., have garnered significant interest as potential alternatives for managing Ganoderma BSR disease. Works done by Angel et al. [63], Muniroh et al. [64], Nurzannah et al. [65], and Wang et al. [66], have emphasised the potential of Trichoderma spp. as biocontrol agents (BCAs) against G. boninense. For instance, T. asperellum exhibited notable suppression of G. boninense growth, resulting in a radial growth inhibition percentage (PIRG) of over 50 % [64]. In another study, T. harzianum was combined with other BCAs, including Lecanicillium spp., Streptomyces sundarbansensis, and Pseudomonas aeruginosa as biocontrol formulation [67]. Treatment with this method significantly decreased ergosterol concentration in the samples compared to the control, showing its potential efficacy in combating G. boninense. Nevertheless, in the nursery trial by Alexander et al. [68], the bioformulation contained a combination of Trichoderma spp. and Bacillus spp. did not demonstrate any inhibitory effects on G. boninense. This highlights the need for careful selection and thorough evaluation of BCAs to determine their efficacy. Although biocontrol therapies are commonly perceived as new and environmentally friendly options, there is a shortage of substantial evidence regarding their effectiveness in field testing. Their efficiency can be influenced by several factors, including the genetic diversity of the target pathogen, the ability to colonise different types of soil, susceptibility to climatic conditions, and interactions with non-target organisms [[69], [70], [71]]. Furthermore, the development of mutant strains of BCAs with reduced efficacy must be carefully considered.

Chemical treatments, such as the application of fungicides, are essential for efficient Ganoderma BSR disease control in agricultural fields. These treatments employ several modes of action to target the pathogenic fungi [72,73] specifically. These include copper-based compounds, dithiocarbamates, and azoles, each possessing distinct advantages and potential drawbacks [4]. Copper-based fungicides liberate copper ions that exhibit toxicity toward a broad spectrum of fungi [72,73]. They are available in many forms, such as copper hydroxide, copper oxychloride, and Bordeaux combination [74]. Nevertheless, the effectiveness of copper-based compounds against Ganoderma spp. can differ, and their application may pose risks to beneficial soil microbes and trigger phytotoxicity in certain plant species [75]. Dithiocarbamates are another type of fungicide that is known for its ability to control a wide range of fungal species effectively. They function by impeding crucial fungal enzymes and suppressing their development [76]. A well-known dithiocarbamate fungicide is Mancozeb, but it carries the risk of developing fungal resistance and causing adverse effects on aquatic ecosystems [77]. Furthermore, the azole fungicide group has proven effective against Ganoderma BSR disease, and its ongoing success in disease management is due to advancements in more potent formulations with a reduced risk of resistance [10,13,78]. This emphasises the importance of azoles in Ganoderma BSR disease management. However, appropriate and sustainable use of these fungicides in the field requires thoughtful consideration of their selection and application.

3 The role of azole-based fungicides in managing fungal pathogens

3.1 Efficacy of azole-based fungicides and their mode of actions

Azoles are a class of chemical compounds that are characterised by their distinctive five-membered ring structure. This ring structure contains one or more nitrogen atoms with or without heteroatoms in the ring and can be classified into several subsets, including triazoles, imidazoles, tetrazoles, pyrimidines and dioxolanes [79]. The agricultural industry experienced a significant transformation in the 1970s with the advent of azole compounds, particularly imazalil (IMZ), which falls within the category of imidazole fungicides [10]. This compound was widely utilised as a seed treatment for potatoes and cereals and a post-harvest treatment for pome fruits, citrus, pineapple, and banana. IMZ effectively inhibited the growth of Penicillium italicum and Penicillium digitatum, which are known to cause storage diseases like blue and green moulds in citrus fruit [80]. Several significant azoles were further discovered to combat various diseases in crops and boost fruit production, namely triadimenol (1973), fenarimol (1975), prochloraz (1977), propiconazole (1979) and bitertanol (1979) [10]. Later, in the early 1980s, the discovery of new azoles, such as prochloraz in Europe, represented a notable advancement in the management of eyespot disease in wheat crops caused by Oculimacula yallundae [81]. The efficacy of these compounds has also been demonstrated in the management of other diseases, including citrus green mold (P. digitatum), rice bakanae disease (F. fujikuroi), and fusarium wilt (F. oxysporum) [10,[82], [83], [84]].

Over time, an increasing number of azole compounds have been synthesised to manage plant diseases in various crops efficiently, demonstrating the continual progress and improvement in fungicide formulations. Flusilazole and Triticonazole, introduced in 1983 and 1995, have shown efficacy in treating powdery mildews and diseases affecting the leaves and ears of cereal crops, respectively. Imibenconazole, which became available in 2011, has been utilised to combat fungal infections in many crops, such as rice and vegetables [10]. Finally, mefentrifluconazole represents a recent addition that specifically targets Septoria tritici blotch (STB), a plant disease caused by the fungal pathogen Zymoseptoria tritici [85,86]. STB is a significant foliar disease in wheat that can lead to substantial yield losses if left uncontrolled. In addition, azole-based fungicides, particularly triazole have consistently proven their effectiveness in providing extended control over various Ganoderma spp. in oil palm, making them valuable tools in disease management strategies. For instance, hexaconazole applications have significantly reduced the severity of BSR induced by G. boninense [87,88]. These findings highlight the importance of different azole fungicides in addressing the challenges posed by Ganoderma spp., ultimately contributing to the resilience and sustainability of the oil palm industry.

Treatment with azole-based fungicides is highly effective in disrupting fungal cell membranes by altering sterol composition. Azoles exert their action by inhibiting the enzyme sterol 14α-demethylase, CYP51, which is a member of the cytochrome P450 family [89,90]. This enzyme is crucial in the ergosterol biosynthetic pathway and essential for the maintenance of fungal membrane fluidity and permeability [13]. Fig. 2 elucidates the process through which azoles disrupt the fungal cell membrane. Azoles initially caused the reduction of ergosterol levels in the fungal cell membrane. Ergosterol is a critical component of fungal membranes, and its decrease significantly affects the membrane properties. Ergosterol contributes to membrane fluidity and stability, and its absence weakens the membrane's structural integrity [91]. Furthermore, the action of azoles in inhibiting CYP51 leads to the buildup of 14α-methylated sterols in the fungal cell membrane. These sterols, devoid of the methyl group at the 14α position, exhibit distinct structural dissimilarities compared to ergosterol. The accumulation of these abnormal sterols disrupts the normal composition of the membrane [90,92]. Consequently, the function of membrane transport mechanisms is impeded, resulting in fungistasis [13]. This is a crucial outcome in disease management, as it prevents the pathogen from causing further damage to the host.Fig. 2 The mode of action of azoles on the fungal membrane. The azole compounds act by inhibiting the synthesis of the sterol components and leading to the accumulation of abnormal sterol (14α-methylated sterol) that destabilises the cell membrane, ultimately resulting in cell lysis and death. Figure created with BioRender.com.

Fig. 2

3.2 Challenges in azole-based fungicide applications

The application of azole-based fungicide is considered crucial and widely used in agricultural commodities. However, due to the inherent low stability and poor water solubility of azole compounds, many fungicide formulations heavily rely on organic solvents for dissolution and dispersion [93,94]. Unfortunately, these formulations face problems, including burst release and suboptimal delivery, necessitating higher dosages and more frequent applications [95]. These challenges not only compromise their disease control efficacy but also raise concerns about environmental contamination through runoff into water bodies and posing health risks to non-target organisms. A comprehensive investigation has been conducted to evaluate the extent of azole contamination and its associated risks. For instance, studies in China found that azole fungicides, such as tebuconazole and tricyclazole, were found in agriculturally intensive regions, indicating their widespread presence in aquatic ecosystems [27,66,96,97]. Similarly, European assessments by the European Topic Centre on Inland, Coastal and Marine water confirmed the presence of azole fungicides, particularly tebuconazole, propiconazole and epoxiconazole, in various European lakes, rivers and coastal seas [98]. The widespread detection of azole fungicides in water bodies raises concerns about their potential ecological consequences. These fungicides can adversely affect non-target aquatic organisms and disrupt aquatic ecosystems. Implementing buffer zones, reducing fungicide use, and adopting integrated pest management approaches that include fungicide rotation and alternative disease control methods can help mitigate fungicide contamination in water bodies while safeguarding the environment [99,100].

Moreover, the widespread and excessive use of azole compounds has resulted in decreased sensitivity in the field, fostering the development of mutations and the emergence of resistance within plant fungal pathogens. For instance, cereal powdery mildews caused by Blumeria graminis developed resistance to the azoles triadimefon and triadimenol within four years of their introduction in the late 1970s [10,101]. However, certain azoles like prothiconazole, registered under the Federal Insecticide, Fungicide, and Rodenticide Act in 2022, still offer a satisfactory level of control for powdery mildew, indicating the absence of cross-resistance [[102], [103], [104]]. Subsequently, other concerns regarding the resistance or shifting sensitivity emerged in many plant diseases. For instance, the rapid evolution of azole resistance is observed in the wheat disease Z. tritici, which causes septoria leaf blotch. This resistance is caused by the mutations in the CYP51 enzyme, the target of these fungicides [95,105,106]. Similarly, Botrytis cinerea, a fungal pathogen affecting various crops, has developed resistance to azoles. This resistance has been attributed to the target site of G143A mutation in the CYP51 enzyme, which has raised concerns in fruit and vegetable production [107]. Furthermore, azole resistance has also been identified in the wheat and rice blast fungus (Pyricularia oryzae Triticum), specifically against triazole fungicides like tebuconazole [108]. Resistance mechanisms in this pathogen involve alterations in both CYP51A and CYP51B genes. These mutations can result in alterations in the fungicide's affinity to the enzyme, leading to the development of azole tolerance. Nevertheless, it was discovered that the strategy of fungicide application and the level of intensity in the management program greatly influence the level of resistance [10,109]. Despite the prevalence of azole resistance, the use of azoles has still contributed to approximately a 10 % increase in crop yields [95].

Additionally, azole fungicides can exert detrimental impacts on human health. They have the ability to interfere with the functioning of many enzymes that are part of the CYP superfamily, found in numerous organisms, including humans. This interaction occurs due to the structural resemblances between azoles and naturally occurring substrates that are typically metabolised by human CYPs, namely CYP3A4, CYP2D6, and CYP2C9 [89]. Consequently, this interaction can potentially result in adverse drug reactions, increased drug toxicity, or altered therapeutic effects. For instance, medications metabolised by CYP3A4, such as certain statins, immunosuppressants, and antiretroviral drugs, can be affected by azole-induced inhibition [110]. This requires careful dosage adjustments or alternative treatment options. Notably, CYP19, also known as aromatase, serves as a primary target for many azole fungicides, both in agriculture and medicine. This enzyme plays a vital role in regulating sex hormones, particularly in converting androgens to estrogens during pubertal development [[111], [112], [113], [114]]. Furthermore, cross-resistance is found in Aspergillus fumigatus, a fungal pathogen capable of infecting humans and crops. Mutations in the CYP51A gene of A. fumigatus have been shown to confer resistance not only to therapeutic azoles like posaconazole, itraconazole, voriconazole, and isavuconazole, but also to agricultural azoles such as propiconazole, tebuconazole and cyproconazole [[115], [116], [117]]. This limits the range of antifungal agents that can be used to treat infections. Consequently, this can result in reduced crop yields and economic losses. Therefore, it is imperative to consistently enhance the formulation and delivery strategy to address the shortcomings associated with utilising these fungicides.

4 Recent advances in nanotechnology for fungicide delivery

4.1 Nanoparticle-based fungicides

In recent years, nanotechnology has brought about a profound transformation in the delivery of fungicides within agriculture and across diverse sectors. Although nanotechnology has made significant advancements in the pharmacology and medicine domain [[118], [119], [120], [121]], its exploration in agricultural applications has been comparatively limited. Nanotechnology offers precise and effective methods for delivering fungicides through nanocarrier systems, effectively tackling many persistent issues related to conventional fungicide applications. The nanocarriers, constructed from a variety of materials, such as lipids, polymers, and inorganic materials, possess different attributes, such as pore size, surface properties, and shape, and serve as protective carriers for fungicides [21,122]. Table 2 provides a comprehensive overview of the nanocarriers used for plant pathogen management. These nanocarrier systems offer potential solutions to improve the effectiveness and sustainability of fungicide applications in agriculture. The fungicides' active ingredient is protected from environmental degradation, their solubility is increased, and they can be released in a sustained manner over extended periods. Consequently, the encapsulation maintains the fungicides' efficacy for extended periods, reducing the necessity for frequent applications and mitigating their environmental and health impacts. Besides, their small size in the nanometer range allows for excellent penetration and interaction with pathogens, enhancing their overall efficacy.Table 2 Types of fungicide nanocarriers for plant Pathogen management.

Table 2Nanocarrier	Active Ingredient	Treatment	Composition	Particle size	Ref.	
Lipid-based Nanocarriers	
Liposome	Cymoxanil	Antifungal treatment on Saccharomyces cerevisiae as model target fungal	Cholesterol and stearylamine	128 nm	[123]	
Liposome	Carboxin	Antifungal treatment in potato tubers	Phosphatidylcholines and Tween 20	–	[124]	
SLNs	Carbendazim and tebuconazole	Phaseolus vulgaris seeds	Glyceryl tripalmitate	542 nm	[125]	
Nanoemulsion	Tebuconazole	Penicillium verrucosum infection in maise seeds	Tween 80 and Agnique BL1754 surfactants	168.6–345.3 nm	[126]	
Nanoemulsion	Mancozeb	Inhibition against early blight disease on Stemphylium lycopersici and Sclerotinia sclerotiorum	Guar gam, glycerol, glutaraldehyde	246.6 ± 0.9 nm	[127]	
Nanoemulsion	Clove oil	Inhibition against Neoscytalidium Blight Disease of Carum carvi L.	Tween 80	36.4–57.1 nm	[128]	
Nanoemulsion	Clove, black seed, lemon, and orange oils	Inhibition against grey mold disease on Botrytis cinerea	Tween 80	82.6–131.9 nm	[129]	
Nanoemulsion	Eugenol oil	Antifungal activity against Fusarium oxysporum in cottonseeds	Tween 20	50–120 nm	[130]	
Nanoemulsion	Peppermint oil	Treatment of Early blight disease against Solanum lycopersicum	Tween 80	20–40 nm	[131]	
Polymeric Nanoparticles	
PLGA	Cyazofamid	Inhibition against Phytophthora infestans infections in tomato leaves	Poly lactic-co-glycolic acid (PLGA) and polyvinyl alcohol	126 ± 8 nm	[132]	
PLGA	Coumarin	Inhibition against grapevine-pathogenic fungi and Vitis vinifera	Poly lactic-co-glycolic acid	30–600 nm	[133]	
Lignin	azoxystrobin, pyraclostrobin, tebuconazole, and boscalid	Antifungal activity against Phaeomoniella chlamydospora and Phaeoacremonium minimum	Lignin methacrylate, spermine and spermidine	170–230 nm	[134]	
Chitosan	Hexaconazole and dazomet	Treatment against Ganoderma boninense on basal stem rot disease	Chitosan, sodium tripolyphosphate and Tween 80	6.5–220.2 nm	[15,88]	
Chitosan	Thymol	Antifungal activity against Botrytis cinerea	Chitosan and sodium tripolyphosphate	<200 nm	[135]	
Polymeric micelles	Geranylorcinol compounds	Antifungal activity against Botrytis cinerea	Pluronic F-127 and poly (ethylene oxide)-b-poly(caprolactone)	–	[136]	
Inorganic Nanoparticles	
Mesoporous silica	Thifluzamide	Prevent negative effects of antifungal activity in rice seedlings	Cetyltrimethylammonium bromide, tetraethyl orthosilicate and n-[3-(Trimethoxysilyl)propyl] ethylenediamine	80–120 nm	[137]	
Mesoporous silica	Prochloraz	Smart management of wilt disease against Rhizoctonia solani	Cellulose, 3-aminopropyltriethoxy silane, tetraethyl orthosilicate, cetyl trimethyl ammonium bromide	255.0 ± 5.3 nm, 531.2 ± 4.9 nm	[138]	
Silica nanoparticle	Silica	Antifungal activity against Fusarium oxysporum and Aspergillus niger	Silica powder from sugarcane bagasse and corn cob	17.23 nm	[139]	
Silver nanoparticle	Silver	Antifungal activity on phytopathogenic citrus fruit fungi against Alternaria alternata, Alternaria citri and Penicillium digitatum	Silver nitrate and polyvinyl pyrrolidone (PVP40)	10 ± 5 nm	[140]	
Silver nanoparticle	Silver	Antifungal activity against Fusarium avenaceum and Fusarium equiseti	Silver nitrate, trisodium citrate dihydrate, sodium borohydride, and cysteamine hydrochloride	12 ± 4 nm, 15 ± 4 nm	[141]	
Magnetite nanoparticle	Iron oxide	Treatment on Fusarium wilt against Fusarium oxysporum f. sp. lycopersici	Burned spinach powder	∼20 nm	[142]	
Iron oxide nanoparticle	Iron oxide	Antifungal activity against Aspergillus niger and Mucor piriformis	Iron oxide and leaf extract Platanus orientalis	38 nm	[143]	
Copper nanoparticles	Copper	Antifungal activity against Fusarium solani, Neofusicoccum sp., and Fusarium oxysporum	Copper (II) sulfate pentahydrate and ascorbic acid	200–500 nm	[144]	

Lipid-based nanocarriers, such as nanoemulsions, liposomes, nanostructured lipid carriers (NLCs), and solid lipid nanoparticles (SLNs), are known for their ability to encapsulate hydrophobic fungicides within their lipid structures, effectively addressing the challenge of distributing these compounds in agriculture. Surfactants are used to stabilise the nanocarriers when dispersed into water. They mitigate the reliance on organic solvents commonly used to dissolve the compounds, promoting environmentally friendly and safer fungicide applications. These nanocarriers enhance the mobility of fungicide active compounds through lipid interactions, facilitating controlled release. For example, Zhang et al. [123] developed a liposomal system incorporating cholesterol and stearylamine to encapsulate cymoxanil, resulting in significantly improved fungicide stability and controlled release. Additionally, SLNs made from glyceryl tripalmitate have demonstrated utility in enhancing the delivery of fungicides like carbendazim and tebuconazole, effectively mitigating burst release and toxicity concerns [125]. Their strong adhesion to plant surfaces reduces runoff, ensuring better disease control. Furthermore, nanoemulsion formulations, consisting of a mixture of nonionic (Tween 80) and anionic (Agnique BL1754) surfactants with fungicide tebuconazole, are prominent for their enhanced solubility and user-friendly application. Mosa et al. demonstrated the efficacy of an eco-friendly nanoemulsion composed of water, Nigella sativa (black seed) oil, and nonionic surfactants, namely Tween 20 and Tween 80, in outperforming the control in inhibiting the growth of Penicillium verrucosum infection in maize seeds [126].

Polymeric nanoparticles have emerged as promising fungicide carriers, with notable studies focusing on materials like chitosan and polylactic-co-glycolic acid (PLGA). The utilisation of these nanoparticles has demonstrated considerable promise in augmenting the efficacy of fungicides across several applications. Chitosan, a biopolymer made from chitin, possesses several desirable characteristics such as biodegradable, biocompatible, non-toxic, and effectively combatting a wide range of plant diseases [[145], [146], [147], [148]]. These exceptional properties have positioned chitosan as a prominent material for nanoparticle development, rendering it a highly favourable option for a wide range of cutting-edge applications. According to a study conducted by Maluin et al. [88], it was shown that the chitosan-loaded hexaconazole nanoparticles with a diameter of 68.1 nm exhibited the highest efficacy in combating G. boninense. These nanoparticles achieved an EC50 value of 8 ppb, significantly outperforming pure hexaconazole with an EC50 value of 21.4 ppb. Their subsequent field trials, in combination with dazomet, demonstrated a noteworthy decrease in the occurrence of basal stem rot disease caused by G. boninense, with a reduction of up to 74.5 % [15]. This demonstrates the prospective application of combined nanofungicides for efficient disease control. Moreover, chitosan nanoparticles synthesised through the ionic gelation technique have effectively controlled rice blast diseases caused by Phyricularia grisea and Phyricularia oryzae [149,150]. Chitosan nanoparticles containing low-water soluble fungicides have also been reported for their effectiveness in combating Fusarium wilt of chickpea [151], and Fusarium crown and root rot in tomatoes [152,153] caused by F. oxysporum.

In a study conducted by Fukamachi et al. [132], they developed PLGA nanoparticles loaded with the cyazofamid fungicide. These nanoparticles demonstrated remarkable fungicidal efficacy when used against Phytophthora infestans infections in tomato leaves. They found that the PLGA nanoparticles exhibited thermodynamically favourable characteristics that promoted their stable attachment to tomato leaves even after simulated rainfall and were highly effective against P. infestans. In another study, Valletta et al. [133] demonstrated that PLGA nanoparticles can penetrate the cell wall and membrane of grapevine-pathogenic fungi (Vitis vinifera) through TEM analysis. They found that the cell wall selectively allows nanoparticles with an average diameter of 30–50 nm to enter the interior cytoplasm while bigger nanoparticles remain attached to the cell wall. In addition to chitosan and PLGA, MacHado et al. [154] have developed a bio-based polymeric nanocarrier made from lignin to encapsulate various fungicides, including azoxystrobin, pyraclostrobin, tebuconazole, and boscalid. These nanocarriers with a 200–300 nm diameter showed high encapsulation efficiencies, reaching up to 99 % depending on the solubility of the active ingredients. These carriers demonstrated strong inhibitory effects against the growth of Phaeoacremonium minimum and Phaeomoniella chlamydospora, both of which are lignin-producing fungi linked to the prevalent fungal grapevine trunk disease known as Esca.

In recent years, the utilisation of inorganic or metallic nanoparticles, particularly silver nanoparticles (AgNPs), has garnered considerable interest within the area of fungicides and their delivery. One key advantage of AgNPs in agriculture is their green synthesis, which aligns with sustainable practices. AgNPs can be synthesised using eco-friendly methods that employ various biological sources, including plant extracts, bacteria, fungi, or yeast, to efficiently convert silver ions into AgNPs [[155], [156], [157]]. This process significantly reduces the reliance on toxic chemicals in nanoparticle production. They can encapsulate or adsorb fungicidal compounds, enhancing their stability and targeted delivery to plant surfaces or fungal pathogens. AgNPs at a concentration of 75 ppm successfully inhibit the growth of mycelium and the germination of spores in four kiwifruit rot-causing pathogens, including Pestalotiopsis microspore, Botryosphaeria dothidea, Alternaria alternata and Diaporthe actinidiae. The AgNPs were found to increase the permeability of the mycelium's cellular membrane, resulting in intracellular substance leakage [157]. Similarly, AgNPs at a concentration of 150 ppm were found to have strong antifungal activity against fungal pathogens isolated from fruit spots and citrus leaf, specifically P. digitatum, A. citri, and A. alternata, when compared to the fungicides iprodione and difenoconazole solution [140].

Moreover, AgNPs and other metallic nanoparticles, such as copper nanoparticles (CuNPs) embedded with natural fungicide chitosan, in inhibiting the growth of pathogenic fungi has been extensively demonstrated. These nanoparticles have shown remarkable efficacy against fungi, including F. oxysporum and Neoscytalidium dimidiatum, which are known to cause significant damage to various crops [[158], [159], [160]]. In another study, CuNPs have also been widely tested for the antifungal activities on different pathogenic fungal species, including F. oxysporum, F. solani and Neofusicoccum sp [72,144,161,162]. These studies highlight the versatility of CuNPs as effective antifungal agents with potential applications across different fungal pathogens, further highlighting their promise in agriculture. These findings suggest that nanoparticles could significantly advance fungicide delivery in agriculture, particularly azoles, similar to their successful applications in the biomedical fields.

4.2 Mechanism of nanodelivery of Azole in fungicide management

The mechanism of nanodelivery of azole fungicides begins with encapsulating these hydrophobic compounds within nanocarriers. The compounds are entrapped or loaded into the structure of nanoparticles during the encapsulation process. The choice of nanocarrier depends on factors like the azole's properties and the desired delivery system. Many azoles suffer from limited solubility in water, which can hinder their efficacy in disease management [94,[163], [164], [165]]. Nanocarriers are pivotal in addressing this challenge by providing a hydrophilic shell or matrix surrounding the hydrophobic fungicide molecules. This encapsulation increases the fungicide's solubility for better distribution, ensuring thorough coverage during fungicide application and reaching all plant parts [166,167]. Crop injury may occur when some areas receive excess fungicide, resulting in phytotoxicity and potential yield loss [168]. Conversely, insufficient coverage or suboptimal delivery can lead to poor protection and the development of fungal resistance [172,173], thus jeopardising crop health and productivity. Hence, this encapsulation ensures that the fungicide remains stable and effective over extended periods. In work conducted by Gao et al. [169], they utilised this approach with difenoconazole, a commonly used triazole fungicide known for its poor water solubility. Through the formation of a β-cyclodextrin inclusion complex, they successfully improved both its solubility and fungicidal efficacy. Similarly, a recent study by Ahmad et al. [170] developed a nanoemulsion formulation with increased solubility of ketoconazole and demonstrated superior effectiveness compared to ketoconazole alone.

The rate of fungicides release from nanocarriers can be affected by variables like the type of nanocarrier, the size of the nanoparticles, and the environment in which they are applied. For instance, Wanyika [171] demonstrated that metalaxyl encapsulated in mesoporous silica nanoparticles showed an increased release rate in water (47 %) compared to soil (11.5 %). In another study, the release rate of tebuconazole from cross-linked lignin nanocarriers was found to be dependent on the ratio of fungicide to lignin sulfonate [134]. Overall, nanocarriers can improve the release rate of fungicides in plants by providing a controlled and sustained release, which can enhance the fungicide's overall efficacy while reducing the amount of fungicide required. The controlled release mechanism allows for the gradual and consistent delivery of the active ingredient over an extended period, maintaining effective concentrations of the fungicide within the plant system for longer durations. Furthermore, these nanocarriers can be engineered to break down into non-toxic components or beneficial by-products after delivering their payload, minimising their environmental footprint. Ahmad Aljafree et al. [172] demonstrated this with nano metal-organic frameworks (MOFs) for the delivery of hexaconazole. Their study showed prolonged fungicidal activity against G.boninense, reducing the need for repeated applications. Remarkably, the progression of Ganoderma BSR disease was completely halted after 26 weeks of in vivo nursery trial and seedling growth was accelerated due to additional nutrients from the disassembly of the MOF carrier system in the soil [172]. This dual function of effective disease management and improved plant health offers a promising solution for sustainable agriculture.

Moreover, nanoformulation can improve the adhesion of azole to plant surfaces, decreasing the likelihood of these chemicals being washed away into waterways or leaching into the soil. This adherence reduces environmental contamination and ensures that the azoles are effectively utilised where they are needed. Research by Yao et al. [173] highlighted that nanosuspension azoxystrobin formulation improved the retention of fungicides and reduced contact angle, indicating enhanced wettability and adhesion capability on plant surfaces, thereby reducing potential run-off and environmental contamination. This, in turn, minimises the toxicity and environmental impact associated with fungicide run-off and contamination of soil and water. In addition, functionalizing nanocarriers with ligands or surface modifications allows for site-specific targeting, increasing the fungicide's effectiveness while minimising off-target effects [163,174]. Fig. 3 illustrates the varieties of nanoparticles and their potential uptake pathways within plant systems. These nanoparticles can be administered directly to seeds, applied through soil drenching for root absorption, or delivered via foliar sprays for leaf absorption. The small size of nanocarriers enables them to distribute evenly and penetrate plant tissues effectively. This enhanced bioavailability allows the fungicide to reach target sites within the plant, such as fungal pathogens or vulnerable plant tissues, with greater precision. The improved bioavailability enhances the fungicide's overall efficacy. Reduced fungicide usage aligns with sustainable agricultural practices.Fig. 3 The application of nanocarrier in fungicide delivery. (A) The types of nanoparticles employed for fungicides encapsulation and delivery, (B) intricate the transportation pathways of nanoparticles in plants through foliar and root uptakes. Figure created with BioRender.com.

Fig. 3

5 Opportunities and challenges in azole-based nanofungicides

Despite the prospects of nanotechnology to revolutionise azole-based fungicide delivery, there remain several key challenges that need to be addressed. Ensuring the stability of azole-based nanofungicide formulations over time can be a challenge, particularly for lipid-based nanocarriers. The susceptibility of the nanocarriers to variations in environmental conditions, such as pH and temperature, can greatly undermine their stability and efficacy [[175], [176], [177]]. One approach to enhancing stability involves the careful selection of lipid excipients based on their Hydrophilic-Lipophilic Balance (HLB). Lipid excipients with appropriate HLB values can form more stable emulsions, improving the consistency and longevity of nanofungicide formulations [178]. Additionally, using mixed surfactants can further increase stability by providing higher molecular interactions between them that enhance the integrity of the nanocarrier structure under varying environmental conditions [178,179]. This was proved by Chang and McClements when using medium chain triglyceride (MCT) and orange oil, the smallest droplets nanocarrier were formed in the system containing Tween 80 and 60, belonging to HLB values of 15.0 and 14.9, respectively [180]. This is in agreement with other studies showing that the most stable and smallest lipid-based carrier system was produced with an HLB value of 13.4, achieved by changing ratios between Tween 80 and Span 20 to 3:1 [181]. This emphasises the need for meticulous excipient selection, quality control, and stability studies to prevent any premature release and suboptimal delivery of azoles.

Efforts to develop sustainable, low-cost methods for synthesising nanoparticles and more research on the interaction mechanism of nanoparticles with crops at the molecular level are needed to make this technology accessible and feasible for agriculture applications. In addition, the long-term environmental impact of nanotechnology remains a subject of concern. The nanocarrier systems and azole residues may persist in soil for extended periods primarily due to their small size and resistance to microbial degradation. This persistence can cause the accumulation of these materials in agricultural fields over time, potentially affecting soil health and the land's long-term productivity. The residues may leach into groundwater, introducing the potential for contamination of water bodies. Besides, the degradation rate of the nanocarrier may vary depending on the choice of their composition and conditions, including the type of surfactant, polymer, temperature, and pH level, all of which have the potential to affect their structural integrity and performance in the field [88,182]. Surfactants such as lecithin degrade more rapidly compared to synthetic counterparts like polysorbate 80, while polymers such as PLA exhibit a slower degradation rate than PLGA due to differences in their hydrolysis rates [183]. On top of that, elevated temperatures can accelerate the degradation of nanomaterial, as seen in hyperthermia treatments [184] and pH levels further influence degradation, with alkaline environments accelerating the breakdown of polymers than neutral conditions [185]. Collectively, these factors are pivotal in determining the structural integrity and efficacy of nanocarriers in agricultural settings. Hence, it is crucial to take into account concerns related to the composition and development of nanocarrier systems that can specifically target plant pathogens while minimising unintended consequences.

The emergence of resistance is a crucial issue that needs immediate attention. An over-reliance on azole-based nanofungicides may lead to the development of resistance in fungal populations, thereby posing a significant challenge to long-term disease management. To address this, it is imperative to encourage an integrated approach by combining various disease management strategies. This approach includes cultural practices, the rotation and mixing of fungicides, the use of biological controls through biopesticides, and the development of disease-resistant crop varieties. Furthermore, the use of nanocarrier systems can significantly enhance the delivery and effectiveness of fungicides, thereby mitigating the risk of resistance and ensuring the sustainable application of nanotechnology in agriculture. Additionally, fostering interdisciplinary collaborations between scientists, agronomists, environmental researchers, and policymakers is crucial to advancing this field. This collaborative approach can lead to the design of novel azole compounds and nanocarrier systems with enhanced efficiency and safety profiles. Besides, it is also essential to establish guidelines and regulations governing the use of nanoparticles in the delivery of fungicides, particularly azoles, to ensure their responsible and sustainable deployment in oil palm plantations. Concurrently, it is imperative to establish acceptable limits for nanocarriers and azole residues by implementing more accurate screening and detection methods. Researchers and industry experts must meticulously evaluate their choice of azole compounds and nanocarrier systems, considering the intricate dynamics of crop-pathogen interactions, ecological aspects, and adherence to regulatory standards. In doing so, we can harness the full potential of azole-based nanofungicides while mitigating any associated risks to agriculture and the environment.

6 Conclusions

Pathogenic fungi present an ongoing threat to oil palm production and exhibit exceptional persistence. Azole-based fungicides were used for nearly half a century to effectively manage oil palm infections and reduce agricultural losses caused by plant diseases. However, this threat is progressively escalating because of growing issues with suboptimal delivery, resistance and the emergence of diseases that threaten arable output. The utilisation of nanotechnology provides an excellent opportunity to improve the effectiveness and long-term viability of disease control. Encapsulating azole-based fungicides within nanocarriers has enhanced fungicidal action, minimised environmental impact, and improved bioavailability. As research in this field continues to evolve, it is clear that nanodelivery systems have the potential to revolutionise the approach to combat diseases, ultimately leading to improved crop yields, economic sustainability, and environmental conservation. Hence, further exploration and development in the nanodelivery of azole-based fungicides are needed for future innovations in oil palm disease management.

Data availability statement

Data will be made available on request.

CRediT authorship contribution statement

Azren Aida Asmawi: Writing – original draft, Visualization, Investigation, Data curation, Conceptualization. Fatmawati Adam: Writing – review & editing, Supervision, Investigation, Conceptualization. Nurul Aini Mohd Azman: Writing – review & editing, Supervision, Investigation, Conceptualization. Mohd Basyaruddin Abdul Rahman: Writing – review & editing, Supervision.

Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fatmawati Adam reports financial support was provided by Universiti Malaysia Pahang Al-Sultan Abdullah, Malaysia. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgement

The authors would like to express gratitude to 10.13039/501100005605 Universiti Malaysia Pahang Al-Sultan Abdullah for funding this work through internal grant number RDU223012 .
==== Refs
References

1 Statista Global production volume palm oil 20222/23 2023 https://www.statista.com/statistics/613471/palm-oil-production-volume-worldwide/
2 Kadir G. Parveez A. Nur Kamil N. Norliyana Zawawi Z. Ong-Abdullah Meilina Rasuddin Rahmahwati Soh Loh K. Kanga Selvaduray R. Seng S. Hoong Idris Z. Oil palm economic performance in Malaysia and R&D progress in 2021 J. Oil Palm Res. 34 2022 185 218 10.21894/jopr.2022.0036
3 Cheah W.Y. Siti-Dina R.P. Leng S.T.K. Er A.C. Show P.L. Circular bioeconomy in palm oil industry: current practices and future perspectives Environ. Technol. Innov. 30 2023 103050 10.1016/J.ETI.2023.103050
4 Khoo Y.W. Chong K.P. Ganoderma boninense: general characteristics of pathogenicity and methods of control Front. Plant Sci. 14 2023 1 17 10.3389/fpls.2023.1156869
5 Darlis D. Jalloh M.B. Chin C.F.S. Basri N.K.M. Besar N.A. Ahmad K. Rakib M.R.M. Exploring the potential of Bornean polypore fungi as biological control agents against pathogenic Ganoderma boninense causing basal stem rot in oil palm Sci. Reports 13 2023 1 10 10.1038/s41598-023-37507-0 2023 131
6 Jazuli N.A. Kamu A. Chong K.P. Gabda D. Hassan A. Abu Seman I. Ho C.M. A review of factors affecting Ganoderma basal stem rot disease progress in oil palm Plants 11 2022 10.3390/PLANTS11192462
7 Zakaria L. Basal stem rot of oil palm: the pathogen, disease incidence, and control methods Plant Dis. 107 2023 603 615 10.1094/PDIS-02-22-0358-FE 35819350
8 Azmi A.N.N. Bejo S.K. Jahari M. Muharam F.M. Yule I. Husin N.A. Early detection of Ganoderma boninense in oil palm seedlings using support vector machines Remote Sens 12 2020 3920 10.3390/RS12233920
9 Paterson R.R.M. Ganoderma boninense disease of oil palm to significantly reduce production after 2050 in sumatra if projected climate change occurs Microorganisms 7 2019 10.3390/MICROORGANISMS7010024
10 Jørgensen L.N. Heick T.M. Azole use in agriculture, horticulture, and wood preservation – is it indispensable? Front. Cell. Infect. Microbiol. 11 2021 1 16 10.3389/fcimb.2021.730297
11 Monk B.C. Keniya M.V. Roles for structural biology in the discovery of drugs and agrochemicals targeting sterol 14α-demethylases J. Fungi 7 2021 1 36 10.3390/JOF7020067
12 Campestre C. Locatelli M. Guglielmi P. De Luca E. Bellagamba G. Menta S. Zengin G. Celia C. Di Marzio L. Carradori S. Sterol 14α-demethylase ligand-binding pocket-mediated acquired and intrinsic azole resistance in fungal pathogens J. Fungi 7 2020 1 10.3390/JOF7010001
13 Price C.L. Parker J.E. Warrilow A.G. Kelly D.E. Kelly S.L. Azole fungicides – understanding resistance mechanisms in agricultural fungal pathogens Pest Manag. Sci. 71 2015 1054 1058 10.1002/PS.4029 25914201
14 Burks C. Darby A. Londoño L.G. Momany M. Brewer M.T. Azole-resistant Aspergillus fumigatus in the environment: identifying key reservoirs and hotspots of antifungal resistance PLoS Pathog. 17 2021 e1009711 10.1371/JOURNAL.PPAT.1009711
15 Maluin F.N. Hussein M.Z. Azah Yusof N. Fakurazi S. Idris A.S. Zainol Hilmi N.H. Jeffery Daim L.D. Chitosan-based agronanofungicides as a sustainable alternative in the basal stem rot disease management J. Agric. Food Chem. 68 2020 4305 4314 10.1021/ACS.JAFC.9B08060/ASSET/IMAGES/LARGE/JF9B08060_0007.JPEG 32227887
16 Zubrod J.P. Bundschuh M. Arts G. Brühl C.A. Imfeld G. Knäbel A. Payraudeau S. Rasmussen J.J. Rohr J. Scharmüller A. Smalling K. Stehle S. Schulz R. Schäfer R.B. Fungicides: an overlooked pesticide class? Environ. Sci. Technol. 53 2019 3347 3365 10.1021/ACS.EST.8B04392/SUPPL_FILE/ES8B04392_SI_001.PDF 30835448
17 Hazra R.S. Roy J. Jiang L. Webster D.C. Rahman M.M. Quadir M. Biobased, macro-, and nanoscale fungicide delivery approaches for plant fungi control ACS Appl. Bio Mater. 6 2023 2698 2711 10.1021/acsabm.3c00171
18 Kumar S. Nehra M. Dilbaghi N. Marrazza G. Hassan A.A. Kim K.H. Nano-based smart pesticide formulations: emerging opportunities for agriculture J. Control. Release. 294 2019 131 153 10.1016/j.jconrel.2018.12.012 30552953
19 Barcelos E. De Almeida Rios S. Cunha R.N.V. Lopes R. Motoike S.Y. Babiychuk E. Skirycz A. Kushnir S. Oil palm natural diversity and the potential for yield improvement Front. Plant Sci. 6 2015 1 16 10.3389/FPLS.2015.00190 25653664
20 John Martin J.J. Yarra R. Wei L. Cao H. Oil palm breeding in the modern era: challenges and opportunities Plants 11 2022 10.3390/PLANTS11111395
21 Maluin F.N. Hussein M.Z. Idris A.S. An overview of the oil palm industry: challenges and some emerging opportunities for nanotechnology development Agronomy 10 2020 10.3390/AGRONOMY10030356
22 Khor J.F. Ling L. Yusop Z. Chin R.J. Lai S.H. Kwan B.H. Ng D.W.K. Impact comparison of el niño and ageing crops on Malaysian oil palm yield Plants 12 2023 10.3390/PLANTS12030424
23 Murphy D.J. Goggin K. Paterson R.R.M. Oil palm in the 2020s and beyond: challenges and solutions CABI Agric. Biosci. 2 2021 1 22 10.1186/S43170-021-00058-3/TABLES/2
24 Xin Y. Sun L. Hansen M.C. Oil palm reconciliation in Indonesia: balancing rising demand and environmental conservation towards 2050 J. Clean. Prod. 380 2022 135087 10.1016/J.JCLEPRO.2022.135087
25 Shigetomi Y. Ishimura Y. Yamamoto Y. Trends in global dependency on the Indonesian palm oil and resultant environmental impacts Sci. Reports 10 2020 1 11 10.1038/s41598-020-77458-4 2020 101
26 Voora V. Bermúdez S. Farrell J.J. Larrea C. Luna E. Palm Oil Prices and Sustainability SUSTAINABLE COMMODITIES MARKETPLACE SERIES 2023
27 Xu Y. Yu L. Li W. Ciais P. Cheng Y. Gong P. Annual oil palm plantation maps in Malaysia and Indonesia from 2001 to 2016 Earth Syst. Sci. Data 12 2020 847 867 10.5194/ESSD-12-847-2020
28 Sundram S. Azni Intan-Nur A.M. South American Bud rot: a biosecurity threat to South East Asian oil palm 10.1016/j.cropro.2017.07.010 2017
29 RSPO Principles & Criteria Certification for the Production of Sustainable Palm Oil 2018 1 134
30 Mohd Hanafiah K. Abd Mutalib A.H. Miard P. Goh C.S. Mohd Sah S.A. Ruppert N. Impact of Malaysian palm oil on sustainable development goals: co-benefits and trade-offs across mitigation strategies Sustain. Sci. 174 17 2021 1639 1661 10.1007/S11625-021-01052-4 2021
31 De Assis Costa O.Y. Tupinambá D.D. Bergmann J.C. Barreto C.C. Quirino B.F. Fungal diversity in oil palm leaves showing symptoms of Fatal Yellowing disease PLoS One 13 2018 e0191884 10.1371/JOURNAL.PONE.0191884
32 Flood J. Bridge P.D. Pilotti C.A. Basal stem rot of oil palm revisited Ann. Appl. Biol. 181 2022 160 181 10.1111/AAB.12772
33 Chidi N.I. Adekunle A.A. Samuel T.O. Eziashi E.I. Molecular identification of secreted effector genes involved in african Fusarium oxysporum f.sp. elaeidis strains pathogenesis during screening Nigerian susceptible and tolerant oil palm (elaeis guineensis jacq.) genotypes Front. Cell. Infect. Microbiol. 10 2020 552394 10.3389/FCIMB.2020.552394
34 Daval A. Pomiès V. Dossa J.S.B. Riou V. Lopez D. Poncet C. Pernaci M. Cochard B. Jacob F. Billotte N. Tisné S. Identification of Fusarium wilt resistance loci in two major genetic backgrounds for oil palm breeding Ind. Crops Prod. 187 2022 10.1016/J.INDCROP.2022.115291
35 Pham M.T. Huang C.M. Kirschner R. First report of the oil palm disease fungus Marasmius palmivorus from Taiwan causing stem rot disease on native Formosa palm Arenga engleri as new host Lett. Appl. Microbiol. 70 2020 143 150 10.1111/LAM.13257 31785004
36 MPOB Emerging disease – SawitSecure http://sawitsecure.mpob.gov.my/emerging-disease/ 2023
37 Mohamed Azni I.N.A. Sundram S. Ramachandran V. Pathogenicity of Malaysian Phytophthora palmivora on cocoa, durian, rubber and oil palm determines the threat of bud rot disease For. Pathol 49 2019 e12557 10.1111/EFP.12557
38 Maizatul-Suriza M. Dickinson M. Idris A.S. Molecular characterization of Phytophthora palmivora responsible for bud rot disease of oil palm in Colombia World J. Microbiol. Biotechnol. 35 2019 10.1007/S11274-019-2618-9
39 Rashid Mohd Rakib M. Joseph Bong C.F. Khairulmazmi A. Seman Idris A. Genetic and morphological diversity of Ganoderma species isolated from infected oil palms (elaeis guineensis) Int. J. Agric. Biol. 2014 http://www.fspublishers.org
40 Anuar M.A.S.S. Ali N.S. Significant oil palm diseases impeding global industry: a review Sains Malays. 51 2022 707 721 10.17576/jsm-2022-5103-06
41 Hushiarian R. Yusof N.A. Dutse S.W. Detection and control of Ganoderma boninense: strategies and perspectives SpringerPlus 2 2013 1 12 10.1186/2193-1801-2-555 23419944
42 Pornsuriya C. Sunpapao A. N.S.-P.P., U A survey of diseases and disorders in oil palms of southern Thailand J. Plant Pathol. 12 2013 169 175 2013 https://www.cabdirect.org/cabdirect/abstract/20143115132
43 Maizatul-Suriza M. Suhanah J. Madihah A.Z. Idris A.S. Mohidin H. Phylogenetic and pathogenicity evaluation of the marasmioid fungus Marasmius palmivorus causing fruit bunch rot disease of oil palm For. Pathol. 51 2021 1 17 10.1111/efp.12660
44 Haituk S. Withee P. Sangta J. Senwanna C. Khamsaw P. Karunarathna A. Hongsibsong S. Sringarm K. Prasad S.K. Sommano S.R. Cheewangkoon R. Production of non-volatile metabolites from sooty molds and their bio-functionalities Process 10 10 2022 329 10.3390/PR10020329 2022) 329
45 Sunpapao A. Kittimorakul J. Pornsuriya C. Disease Note: identification of Curvularia oryzae as cause of leaf spot disease on oil palm seedlings in nurseries of Thailand Phytoparasitica 42 2014 529 533 10.1007/s12600-014-0390-9
46 Haw Y.H. Lai K.W. Chuah J.H. Bejo S.K. Husin N.A. Hum Y.C. Yee P.L. Tee C.A.T.H. Ye X. Wu X. Classification of basal stem rot using deep learning: a review of digital data collection and palm disease classification methods PeerJ Comput. Sci. 9 2023 1 30 10.7717/PEERJ-CS.1325
47 Wong L.C. Bong C.F.J. Idris A.S. Ganoderma species associated with basal stem rot disease of oil palm Am. J. Appl. Sci. 9 2012 879 885 10.3844/ajassp.2012.879.885
48 Midot F. Lau S.Y.L. Wong W.C. Tung H.J. Yap M.L. Lo M.L. Jee M.S. Dom S.P. Melling L. Genetic diversity and demographic history of Ganoderma boninense in oil palm plantations of Sarawak, Malaysia inferred from ITS regions Microorganisms 7 2019 1 17 10.3390/microorganisms7100464
49 Naidu Y. Siddiqui Y. Rafii M.Y. Saud H.M. Idris A.S. Investigating the effect of white-rot hymenomycetes biodegradation on basal stem rot infected oil palm wood blocks: biochemical and anatomical characterization Ind. Crops Prod. 108 2017 872 882 10.1016/j.indcrop.2017.08.064
50 Woittiez L.S. van Wijk M.T. Slingerland M. van Noordwijk M. Giller K.E. Yield gaps in oil palm: a quantitative review of contributing factors Eur. J. Agron. 83 2017 57 77 10.1016/J.EJA.2016.11.002
51 Majidi M.M. Pour-Aboughadareh A. Huang Y. Russell R. Paterson M. Future climate effects on yield and mortality of conventional versus modified oil palm in SE Asia Plants 12 12 2023 2236 10.3390/PLANTS12122236 2023) 2236 37375863
52 Pilotti C.A. Gorea E.A. Bonneau L. Basidiospores as sources of inoculum in the spread of Ganoderma boninense in oil palm plantations in Papua New Guinea Plant Pathol. 67 2018 1841 1849 10.1111/ppa.12915
53 Lo M.L. Thanh T.A.V. Midot F. Lau S.Y.L. Wong W.C. Tung H.J. Jee M.S. Chin M.Y. Melling L. Comparison of Ganoderma boninense isolate's aggressiveness using infected oil palm seedlings J. Microbiol. 61 2023 449 459 10.1007/S12275-023-00040-W/FIGURES/4 37097587
54 Mohd Hilmi Tan M.I.S. Jamlos M.F. Omar A.F. Dzaharudin F. Chalermwisutkul S. Akkaraekthalin P. Ganoderma boninense disease detection by near-infrared spectroscopy classification: a review Sensors 21 2021 10.3390/S21093052
55 Dzulkafli S.B. Othman A. Lau B.Y.C. Nurazah Z. Nagappan J. Ramli U.S. Karsani S.A. Understanding the effects of carbon and nitrogen starvation on the comparative secretomes of Ganoderma boninense and Ganoderma tornatum Physiol. Mol. Plant Pathol. 127 2023 102084 10.1016/j.pmpp.2023.102084
56 Husin N.A. Khairunniza-Bejo S. Abdullah A.F. Kassim M.S.M. Ahmad D. Azmi A.N.N. Application of ground-based LiDAR for analysing oil palm canopy properties on the occurrence of basal stem rot (BSR) disease Sci. Rep. 10 2020 6464 10.1038/S41598-020-62275-6 32296108
57 Siddiqui Y. Surendran A. Paterson R.R.M. Ali A. Ahmad K. Current strategies and perspectives in detection and control of basal stem rot of oil palm Saudi J. Biol. Sci. 28 2021 2840 2849 10.1016/j.sjbs.2021.02.016 34012325
58 Suwardi L. Sutiarso Wirianata H. Nugroho A.P. Pradiko I. Ginting E.N. Darlan N.H. Syarovy M. Primananda S. Sukarman, Mounding technique improves physiological performance and yield of oil palm on Spodosols Sains Tanah 19 2022 221 229 10.20961/stjssa.v19i2.65460
59 Priwiratama H. Prasetyo A.E. Susanto A. Incidence of basal stem rot disease of oil palm in converted planting areas and control treatments IOP Conf. Ser. Earth Environ. Sci. 468 2020 012036 10.1088/1755-1315/468/1/012036
60 Mathews J. Ng S.K. Lim R.R. Ng J.Y. S M. Methods of land preparation to delay Ganoderma or basal stem rot (bsr) disease in oil palm replanting in Inland mineral soils - experiences and observations Plant 97 2021 200 215 10.56333/tp.2021.020
61 V Hall J. V Zibtsev S. Giglio L. Skakun S. Myroniuk V. Zhuravel O. Goldammer J.G. Kussul N. Cropland Burning in Ukraine vol. 16 2021 064017 10.1088/1748-9326/abfc04.Environmental
62 Virdiana I. Hasan Y. Aditya R. Flood J. Testing the effects of oil palm replanting practices (windrowing, fallowing and poisoning) on incidence of Ganoderma Proceeding of the Indonesian Oil Palm Conference 2010 7
63 Angel L.P.L. Yusof M.T. Ismail I.S. Ping B.T.Y. Mohamed Azni I.N.A. Kamarudin N.H. Sundram S. An in vitro study of the antifungal activity of Trichoderma virens 7b and a profile of its non-polar antifungal components released against Ganoderma boninense J. Microbiol. 54 2016 732 744 10.1007/S12275-016-6304-4 27796927
64 Muniroh M.S. Nusaibah S.A. Vadamalai G. Siddique Y. Proficiency of biocontrol agents as plant growth promoters and hydrolytic enzyme producers in Ganoderma boninense infected oil palm seedlings Curr. Plant Biol. 20 2019 100116 10.1016/j.cpb.2019.100116
65 Nurzannah S.E. Purnamasari I. Siagian D.R. Ramija K.E.L. Potential of Trichoderma and mycorrhizae as biological agents for controlling Ganoderma boninense in oil palm IOP Conf. Ser. Earth Environ. Sci. 974 2022 012097 10.1088/1755-1315/974/1/012097
66 Wang Y. Zeng L. Wu J. Jiang H. Mei L. Diversity and effects of competitive Trichoderma species in Ganoderma lucidum–cultivated soils Front. Microbiol. 13 2022 1067822 10.3389/FMICB.2022.1067822/BIBTEX
67 Japanis F.G. Chan Y.S. Chong K.P. Evaluation on the effectiveness of combination of biocontrol agents in managing Ganoderma boninense of oil palm, Malays J. Microbiol. 17 2021 1 10 10.21161/mjm.190497
68 Alexander A. Lo R.K.S. Chong K.P. The effectiveness of selected biological control agents in controlling Ganoderma boninense J. Sustain. Sci. Manag. 16 2021 128 137 10.46754/jssm.2021.08.011
69 Bonaterra A. Badosa E. Daranas N. Francés J. Roselló G. Montesinos E. Bacteria as biological control agents of plant diseases Microorganisms 10 2022 10.3390/microorganisms10091759
70 Bardin M. Ajouz S. Comby M. Lopez-Ferber M. Graillot B. Siegwart M. Nicot P.C. Is the efficacy of biological control against plant diseases likely to be more durable than that of chemical pesticides? Front. Plant Sci. 6 2015 1 14 10.3389/fpls.2015.00566 25653664
71 Pastor N. Palcious S. Torres A.M. Microbial consortia containing fungal biocontrol agents , with emphasis on Trichoderma spp .: current applications for plant protection and effects on soil microbial communities Eur. J. Plant Pathol. 167 2023 593 620 10.1007/s10658-023-02773-1
72 Ingle A.P. Rai M. Copper nanoflowers as effective antifungal agents for plant pathogenic fungi IET Nanobiotechnol. 11 2017 546 10.1049/IET-NBT.2016.0170 28745287
73 Battiston E. Compant S. Antonielli L. Mondello V. Clément C. Simoni A. Di Marco S. Mugnai L. Fontaine F. In planta activity of novel copper(II)-Based formulations to inhibit the Esca-associated fungus Phaeoacremonium minimum in grapevine propagation material Front. Plant Sci. 12 2021 649694 10.3389/FPLS.2021.649694/BIBTEX
74 Arena M. Auteri D. Barmaz S. Bellisai G. Brancato A. Brocca D. Bura L. Byers H. Chiusolo A. Court Marques D. Crivellente F. De Lentdecker C. Egsmose M. Erdos Z. Fait G. Ferreira L. Goumenou M. Greco L. Ippolito A. Istace F. Jarrah S. Kardassi D. Leuschner R. Lythgo C. Magrans J.O. Medina P. Miron I. Molnar T. Nougadere A. Padovani L. Parra Morte J.M. Pedersen R. Reich H. Sacchi A. Santos M. Serafimova R. Sharp R. Stanek A. Streissl F. Sturma J. Szentes C. Tarazona J. Terron A. Theobald A. Vagenende B. Verani A. Villamar-Bouza L. Peer review of the pesticide risk assessment of the active substance copper compounds copper(I), copper(II) variants namely copper hydroxide, copper oxychloride, tribasic copper sulfate, copper(I) oxide, Bordeaux mixture EFSA J. 16 2018 e05152 10.2903/J.EFSA.2018.5152
75 Keiblinger K.M. Schneider M. Gorfer M. Paumann M. Deltedesco E. Berger H. Jöchlinger L. Mentler A. Zechmeister-Boltenstern S. Soja G. Zehetner F. Assessment of Cu applications in two contrasting soils—effects on soil microbial activity and the fungal community structure Ecotoxicology 27 2018 217 10.1007/S10646-017-1888-Y 29297133
76 Yuli E. Dayou J. Chong K.P. In vitro antifungal activity of thiram against Ganoderma boninense Trans. Sci. Technol. 7 2020 159 164
77 Kumar R. Duhan J.S. Manuja A. Kaur P. Kumar B. Sadh P.K. Toxicity assessment and control of early blight and stem rot of Solanum tuberosum L. By mancozeb-loaded chitosan–gum Acacia nanocomposites J. Xenobiotics. 12 2022 74 90 10.3390/jox12020008
78 Pacholak A. Burlaga N. Frankowski R. Zgoła-Grześkowiak A. Kaczorek E. Azole fungicides: (Bio)degradation, transformation products and toxicity elucidation Sci. Total Environ. 802 2022 149917 10.1016/J.SCITOTENV.2021.149917
79 Teixeira M.M. Carvalho D.T. Sousa E. Pinto E. New antifungal agents with azole moieties Pharm. Times 15 2022 1427 10.3390/PH15111427 15 (2022) 1427
80 Altieri G. Di Renzo G.C. Genovese F. Calandra M. Strano M.C. A new method for the postharvest application of imazalil fungicide to citrus fruit Biosyst. Eng. 115 2013 434 443 10.1016/J.BIOSYSTEMSENG.2013.04.008
81 Van Zaayen A. Van Adrichem J.C.J. Prochloraz for control of fungal pathogens of cultivated mushrooms, Netherlands J Plant Pathol. 88 1982 203 213 10.1007/BF02140883
82 Ramanauskienė J. Gaurilčikienė I. Supronienė S. Effects of fungicides on the occurrence of winter wheat eyespot caused by fungi Oculimacula acuformis and O. yallundae Crop Prot 90 2016 90 95 10.1016/J.CROPRO.2016.08.027
83 Kim S.H. Park M.R. Kim Y.C. Lee S.W. Choi B.R. Lee S.W. Kim I.S. Degradation of prochloraz by rice bakanae disease pathogen Fusarium fujikuroi with differing sensitivity: a possible explanation for resistance mechanism J. Appl. Biol. Chem. 53 2010 433 439 10.3839/jksabc.2010.067
84 Amini J. Dzhalilov F.S. The effects of fungicides on fusarium oxysporum F. SP. lycopersici associated with fusarium wilt of tomato J. Plant Prot. Res. 50 2010 172 178 10.2478/v10045-010-0029-x
85 Klink H. Verreet J.A. Hasler M. Birr T. Will triazoles still be of importance in disease control of zymoseptoria tritici in the future? Agronomy 11 2021 10.3390/agronomy11050933
86 Jørgensen L.N. Matzen N. Heick T.M. O'Driscoll A. Clark B. Waite K. Blake J. Glazek M. Maumene C. Couleaud G. Rodemann B. Weigand S. Bataille C. R B. Hellin P. Kildea S. Stammler G. Shifting sensitivity of septoria tritici blotch compromises field performance and yield of main fungicides in Europe Front. Plant Sci. 13 2022 10.3389/FPLS.2022.1060428
87 Nur-rashyeda R. Idris A.B.U.S. Sundram S. Zainol-hilmi N.U.R.H. Ming S.U.C. A FIELD EVALUATION ON FUNGICIDES 2022
88 Maluin F.N. Hussein M.Z. Yusof N.A. Fakurazi S. Idris A.S. Hilmi N.H.Z. Daim L.D.J. Preparation of chitosan-hexaconazole nanoparticles as fungicide nanodelivery system for combating Ganoderma disease in oil palm Molecules 24 2019 10.3390/MOLECULES24132498
89 Zhang J. Li L. Lv Q. Yan L. Wang Y. Jiang Y. The fungal CYP51s: their functions, structures, related drug resistance, and inhibitors Front. Microbiol. 10 2019 10.3389/FMICB.2019.00691
90 Warrilow A.G. Parker J.E. Kelly D.E. Kelly S.L. Azole affinity of sterol 14α-demethylase (CYP51) enzymes from Candida albicans and Homo sapiens Antimicrob. Agents Chemother. 57 2013 1352 10.1128/AAC.02067-12 23274672
91 Sellers-Moya Á. Nuévalos M. Molina M. Martín H. Clotrimazole-induced oxidative stress triggers novel yeast pkc1-independent cell wall integrity mapk pathway circuitry J. Fungi 7 2021 647 10.3390/JOF7080647/S1
92 Emami S. Tavangar P. Keighobadi M. An overview of azoles targeting sterol 14α-demethylase for antileishmanial therapy Eur. J. Med. Chem. 135 2017 241 259 10.1016/J.EJMECH.2017.04.044 28456033
93 Lakhani P. Patil A. Majumdar S. Challenges in the polyene- and azole-based pharmacotherapy of ocular fungal infections J. Ocul. Pharmacol. Ther. 35 2019 6 10.1089/JOP.2018.0089 30481082
94 Roy I. Thapa M. Goswami A. Nanohexaconazole: synthesis, characterisation and efficacy of a novel fungicidal nanodispersion IET Nanobiotechnol. 12 2018 864 10.1049/IET-NBT.2018.0041 30104464
95 Jørgensen L.N. Matzen N. Heick T.M. Havis N. Holdgate S. Clark B. Blake J. Glazek M. Korbas M. Danielewicz J. Maumene C. Rodemann B. Weigand S. Kildea S. Bataille C. Brauna-Morževska E. Gulbis K. Ban R. Berg G. Semaskiene R. Stammler G. Decreasing azole sensitivity of Z. tritici in Europe contributes to reduced and varying field efficacy J. Plant Dis. Prot. 128 2021 287 301 10.1007/S41348-020-00372-4/FIGURES/7
96 Tan H. Zhang H. Wu C. Wang C. Li Q. Pesticides in surface waters of tropical river basins draining areas with rice–vegetable rotations in Hainan, China: occurrence, relation to environmental factors, and risk assessment Environ. Pollut. 283 2021 117100 10.1016/J.ENVPOL.2021.117100
97 Ye R. Hayes D.G. Burton R. Liu A. Harte F.M. Wang Y. Solvent-free lipase-catalyzed synthesis of technical-grade sugar esters and evaluation of their physicochemical and bioactive properties Catal 6 2016 78 10.3390/CATAL6060078
98 Mohaupt V. Volker J. Kirst I. Pesticides in European rivers, lakes and groundwaters – data assessment ETC/ICM Technical Report 1/2020 https://www.researchgate.net/publication/349284017_Pesticides_in_European_rivers_lakes_and_groundwaters_-_Data_assessment 2020
99 Ortega P. Escolà Casas M. Gil E. Matamoros V. Attenuation and soil biodegradation of fungicides by using vegetated buffer strips in vineyards during a simulated rainfall-runoff event Environ. Sci. Pollut. Res. Int. 30 2023 10.1007/S11356-023-27766-9
100 Pretty J. Bharucha Z.P. Integrated pest management for sustainable intensification of agriculture in Asia and Africa Insects 6 2015 152 10.3390/INSECTS6010152 26463073
101 Senior I.J. Hollomon D.W. Loeffler R.S.T. Baldwin B.C. Sterol composition and resistance to DMI fungicides in Erysiphe graminis Pestic. Sci. 45 1995 57 67 10.1002/PS.2780450109
102 Vielba-Fernández A. Polonio Á. Ruiz-Jiménez L. de Vicente A. Pérez-García A. Fernández-Ortuño D. Fungicide resistance in powdery mildew fungi Microorganisms 8 2020 1 34 10.3390/microorganisms8091431
103 Tucker M.A. Lopez-Ruiz F. Cools H.J. Mullins J.G.L. Jayasena K. Oliver R.P. Analysis of mutations in West Australian populations of Blumeria graminis f. sp. hordei CYP51 conferring resistance to DMI fungicides Pest Manag. Sci. 76 2020 1265 1272 10.1002/ps.5636 31595590
104 U.S. Environmental Protection Agency Prothioconazole 4L https://www3.epa.gov/pesticides/chem_search/ppls/045002-00056-20221221.pdf 2022
105 Gutierrez Vazquez Y. Adams I.P. McGreig S. Walshaw J. van den Berg F. Sanderson R. Pufal H. Conyers C. Langton D. Broadhead R. Harrison C. Boonham N. Profiling azole resistant haplotypes within Zymoseptoria tritici populations using nanopore sequencing Front. Agron. 4 2022 943440 10.3389/FAGRO.2022.943440/BIBTEX
106 McDonald M.C. Renkin M. Spackman M. Orchard B. Croll D. Solomon P.S. Milgate A. Rapid parallel evolution of azole fungicide resistance in Australian populations of the wheat pathogen zymoseptoria tritici Appl. Environ. Microbiol. 85 2019 1908 1926 10.1128/AEM.01908-18
107 Fernández-Ortuño D. Grabke A. Li X. Schnabel G. Independent emergence of resistance to seven chemical classes of fungicides in Botrytis cinerea Phytopathology 105 2015 424 432 10.1094/PHYTO-06-14-0161-R 25317841
108 Poloni N.M. Carvalho G. Nunes Campos Vicentini S. Francis Dorigan A. Nunes Maciel J.L. McDonald B.A. Intra Moreira S. Hawkins N. Fraaije B.A. Kelly D.E. Kelly S.L. Ceresini P.C. Widespread distribution of resistance to triazole fungicides in Brazilian populations of the wheat blast pathogen Plant Pathol. 70 2021 436 448 10.1111/PPA.13288
109 Corkley I. Fraaije B. Hawkins N. Fungicide resistance management: maximizing the effective life of plant protection products Plant Pathol. 71 2022 150 169 10.1111/PPA.13467
110 Zhou Q. Yan X.F. Zhang Z.M. Pan W.S. Zeng S. Rational prescription of drugs within similar therapeutic or structural class for gastrointestinal disease treatment: drug metabolism and its related interactions World J. Gastroenterol. 13 2007 5618 10.3748/WJG.V13.I42.5618 17948937
111 Egbuta C. Lo J. Ghosh D. Mechanism of inhibition of estrogen biosynthesis by azole fungicides Endocrinology 155 2014 4622 4628 10.1210/en.2014-1561 25243857
112 Souza S.A. Held A. Lu W.J. Drouhard B. Avila B. Leyva-Montes R. Hu M. Miller B.R. Ng H.L. Mechanisms of allosteric and mixed mode aromatase inhibitors RSC Chem. Biol. 2 2021 892 905 10.1039/d1cb00046b 34458816
113 Caciolla J. Bisi A. Belluti F. Rampa A. Gobbi S. Reconsidering aromatase for breast cancer treatment: new roles for an old target Molecules 25 2020 5351 10.3390/molecules25225351 33207783
114 Choi J.Y. Podust L.M. Roush W.R. Drug strategies targeting CYP51 in neglected tropical diseases Chem. Rev. 114 2014 11242 11271 10.1021/cr5003134 25337991
115 Hsu T.H. Huang P.Y. Fan Y.C. Sun P.L. Azole resistance and cyp51A mutation of Aspergillus fumigatus in a tertiary referral hospital in taiwan J. Fungi 8 2022 10.3390/JOF8090908
116 Hagiwara D. Watanabe A. Kamei K. Sensitisation of an azole-resistant Aspergillus fumigatus strain containing the Cyp51A-related mutation by deleting the SrbA gene Sci. Rep. 6 2016 1 8 10.1038/srep38833 28442746
117 Verweij P.E. Lucas J.A. Arendrup M.C. Bowyer P. Brinkmann A.J.F. Denning D.W. Dyer P.S. Fisher M.C. Geenen P.L. Gisi U. Hermann D. Hoogendijk A. Kiers E. Lagrou K. Melchers W.J.G. Rhodes J. Rietveld A.G. Schoustra S.E. Stenzel K. Zwaan B.J. Fraaije B.A. The one health problem of azole resistance in Aspergillus fumigatus: current insights and future research agenda Fungal Biol. Rev. 34 2020 202 214 10.1016/j.fbr.2020.10.003
118 Hussain M.H. Abu Bakar N.F. Mustapa A.N. Low K.F. Othman N.H. Adam F. Synthesis of various size gold nanoparticles by chemical reduction method with different solvent polarity Nanoscale Res. Lett. 15 2020 1 10 10.1186/S11671-020-03370-5 31897852
119 Haleem A. Javaid M. Singh R.P. Rab S. Suman R. Applications of nanotechnology in medical field: a brief review Glob. Heal. J. 7 2023 70 77 10.1016/J.GLOHJ.2023.02.008
120 Mazayen Z.M. Ghoneim A.M. Elbatanony R.S. Basalious E.B. Bendas E.R. Pharmaceutical nanotechnology: from the bench to the market Futur. J. Pharm. Sci. 8 2022 12 10.1186/S43094-022-00400-0 35071609
121 Mago A. Junaid Tahir M. Arslan Khan M. Abbasher Hussien Mohamed Ahmed K. Usman Munir M. Nanomedicine: advancement in healthcare Ann. Med. Surg. 79 2022 104078 10.1016/J.AMSU.2022.104078
122 Chandrakala V. Aruna V. Angajala G. Review on metal nanoparticles as nanocarriers: current challenges and perspectives in drug delivery systems Emergent Mater 5 2022 1593 1615 10.1007/s42247-021-00335-x 35005431
123 Zhang Z. Yang J. Yang Q. Tian G. Cui Z.K. Fabrication of non-phospholipid liposomal nanocarrier for sustained-release of the fungicide cymoxanil Front. Mol. Biosci. 8 2021 627817 10.3389/FMOLB.2021.627817/BIBTEX
124 Vasileva L.A. Gaynanova G.A. Nizameev I.R. Petrova A.A. Kadirov M.K. Gorshkova T.A. Zakharova L.Y. Enhanced potato tuber penetration of carboxin via ultradeformable liposomes Food Biosci. Part A 2022 102003
125 Campos E.V.R. De Oliveira J.L. Da Silva C.M.G. Pascoli M. Pasquoto T. Lima R. Abhilash P.C. Fernandes Fraceto L. Polymeric and solid lipid nanoparticles for sustained release of carbendazim and tebuconazole in agricultural applications Sci. Reports 51 5 2015 1 14 10.1038/srep13809 2015
126 Mosa M.A. Youssef K. Hamed S.F. Hashim A.F. Antifungal activity of eco-safe nanoemulsions based on Nigella sativa oil against Penicillium verrucosum infecting maize seeds: biochemical and physiological traits Front. Microbiol. 13 2023 1108733 10.3389/FMICB.2022.1108733/BIBTEX
127 Kumar R. Nehra M. Kumar D. Saharan B.S. Chawla P. Sadh P.K. Manuja A. Duhan J.S. Evaluation of cytotoxicity, release behavior and phytopathogens control by mancozeb-loaded guar gum nanoemulsions for sustainable agriculture J. Xenobiotics. 13 2023 270 283 10.3390/jox13020020
128 Hashem A.H. Abdelaziz A.M. Hassanin M.M.H. Al-Askar A.A. AbdElgawad H. Attia M.S. Potential impacts of clove essential oil nanoemulsion as bio fungicides against Neoscytalidium blight disease of carum carvi L Agronomy 13 2023 10.3390/agronomy13041114
129 Ziedan E.-S.H.E. Saad M.M. El-Kafrawy A.A. Sahab A.F. Mossa A.-T.H. Evaluation of essential oils nanoemulsions formulations on Botrytis cinerea growth, pathology and grey mould incidence on cucumber fruits Bull. Natl. Res. Cent. 46 2022 10.1186/s42269-022-00765-5
130 Abd-Elsalam K.A. Khokhlov A.R. Eugenol oil nanoemulsion: antifungal activity against Fusarium oxysporum f. sp. vasinfectum and phytotoxicity on cottonseeds Appl. Nanosci. 5 2015 255 265 10.1007/s13204-014-0398-y
131 Pandey S. Giri V.P. Tripathi A. Kumari M. Narayan S. Bhattacharya A. Srivastava S. Mishra A. Early blight disease management by herbal nanoemulsion in Solanum lycopersicum with bio-protective manner Ind. Crops Prod. 150 2020 112421 10.1016/j.indcrop.2020.112421
132 Fukamachi K. Konishi Y. Nomura T. Disease control of Phytophthora infestans using cyazofamid encapsulated in poly lactic-co-glycolic acid PLGA) nanoparticles 577 2019 315 322 10.1016/j.colsurfa.2019.05.077
133 Valletta A. Chronopoulou L. Palocci C. Baldan B. Donati L. Pasqua G. Poly(lactic-co-glycolic) acid nanoparticles uptake by Vitis vinifera and grapevine-pathogenic fungi J. Nanoparticle Res. 16 2014 2744 10.1007/s11051-014-2744-0
134 MacHado T.O. Beckers S.J. Fischer J. Müller B. Sayer C. De Araújo P.H.H. Landfester K. Wurm F.R. Bio-based lignin nanocarriers loaded with fungicides as a versatile platform for drug delivery in plants Biomacromolecules 21 2020 2755 2763 10.1021/ACS.BIOMAC.0C00487 32543851
135 Zhao X. Zhang Y. Chen L. Ma Z. Zhang B. Chitosan-thymol nanoparticle with pH responsiveness as a potential intelligent botanical fungicide against Botrytis cinerea Pestic. Biochem. Physiol. 195 2023 105571
136 Taborga L. Díaz K. Olea A.F. Reyes-Bravo P. Flores M.E. Peña-Cortés H. Espinoza L. Effect of polymer micelles on antifungal activity of geranylorcinol compounds against Botrytis cinerea J. Agric. Food Chem. 63 2015 6890 6896 10.1021/acs.jafc.5b01920 26196664
137 Zhao P. Wang C. Zhang S. Zheng L. Li F. Cao C. Cao L. Huang Q. Fungicide-loaded mesoporous silica nanoparticles promote rice seedling growth by regulating amino acid metabolic pathways J. Hazard Mater. 425 2022 127892
138 Huang W. Pan H. Hu Z. Wang M. Wu L. Zhang F. A functional bimodal mesoporous silica nanoparticle with redox/cellulase dual-responsive gatekeepers for controlled release of fungicide Sci. Rep. 13 2023 1 13 10.1038/s41598-023-27396-8 36593249
139 Goswami P. Mathur J. Application of agro-waste-mediated silica nanoparticles to sustainable agriculture Bioresour. Bioprocess. 9 2022 9 10.1186/s40643-022-00496-5 38647762
140 Abdelmalek G.A. Salaheldin T.A. Silver nanoparticles as a potent fungicide for citrus phytopathogenic fungi J. Nanomedicine Res. 3 2016 00065 10.15406/JNMR.2016.03.00065
141 Matras E. Gorczyca A. Przemieniecki S.W. Oćwieja M. Surface properties-dependent antifungal activity of silver nanoparticles Sci. Rep. 12 2022 1 17 10.1038/s41598-022-22659-2 34992227
142 Ashraf H. Batool T. Anjum T. Illyas A. Li G. Naseem S. Riaz S. Antifungal potential of green synthesized magnetite nanoparticles black coffee–magnetite nanoparticles against wilt infection by ameliorating enzymatic activity and gene expression in Solanum lycopersicum L Front. Microbiol. 13 2022 1 23 10.3389/fmicb.2022.754292
143 Devi H.S. Boda M.A. Shah M.A. Parveen S. Wani A.H. Green synthesis of iron oxide nanoparticles using Platanus orientalis leaf extract for antifungal activity Green Process. Synth. 8 2019 38 45 10.1515/gps-2017-0145
144 Pariona N. Mtz-Enriquez A.I. Sánchez-Rangel D. Carrión G. Paraguay-Delgado F. Rosas-Saito G. Green-synthesized copper nanoparticles as a potential antifungal against plant pathogens RSC Adv. 9 2019 18835 18843 10.1039/C9RA03110C 35516870
145 Kumar S. Mukherjee A. Dutta J. Chitosan based nanocomposite films and coatings: emerging antimicrobial food packaging alternatives Trends Food Sci. Technol. 97 2020 196 209 10.1016/j.tifs.2020.01.002
146 Kedir W.M. Abdi G.F. Goro M.M. Tolesa L.D. Pharmaceutical and drug delivery applications of chitosan biopolymer and its modified nanocomposite: a review Heliyon 8 2022 e10196 10.1016/j.heliyon.2022.e10196
147 Desai N. Rana D. Salave S. Gupta R. Patel P. Karunakaran B. Sharma A. Giri J. Benival D. Kommineni N. Chitosan: a potential biopolymer in drug delivery and biomedical applications Pharmaceutics 15 2023 1313 10.3390/pharmaceutics15041313 37111795
148 Teaca C.A. Tanasa F. Zanoaga M. Multi-component polymer systems comprising wood as bio-based component and thermoplastic polymer matrices – an overview Bioresources 13 2018 4728 4769 10.15376/BIORES.13.2.TEACA
149 Manikandan A. Sathiyabama M. Preparation of Chitosan nanoparticles and its effect on detached rice leaves infected with Pyricularia grisea Int. J. Biol. Macromol. 84 2016 58 61 10.1016/J.IJBIOMAC.2015.11.083 26656594
150 Pham T.T. Nguyen T.H. Thi T.V. Nguyen T.T. Le T.D. Vo D.M.H. Nguyen D.H. Nguyen C.K. Nguyen D.C. Nguyen T.T. Bach L.G. Investigation of chitosan nanoparticles loaded with protocatechuic acid (PCA) for the resistance of pyricularia oryzae fungus against rice blast Polymers 11 2019 177 10.3390/POLYM11010177 30960161
151 Sravani B. Dalvi S. Narute T.K. Role of chitosan nanoparticles in combating Fusarium wilt (Fusarium oxysporum f. sp. ciceri) of chickpea under changing climatic conditions J. Phytopathol. 171 2023 67 81 10.1111/JPH.13159
152 Kashyap P.L. Xiang X. Heiden P. Chitosan nanoparticle based delivery systems for sustainable agriculture Int. J. Biol. Macromol. 77 2015 36 51 10.1016/J.IJBIOMAC.2015.02.039 25748851
153 Benhamou N. Thériault G. Treatment with chitosan enhances resistance of tomato plants to the crown and root rot pathogen Fusarium oxysporum f. sp. radicis-lycopersici Physiol. Mol. Plant Pathol. 41 1992 33 52 10.1016/0885-5765(92)90047-Y
154 MacHado T.O. Beckers S.J. Fischer J. Müller B. Sayer C. De Araújo P.H.H. Landfester K. Wurm F.R. Bio-based lignin nanocarriers loaded with fungicides as a versatile platform for drug delivery in plants Biomacromolecules 21 2020 2755 2763 10.1021/acs.biomac.0c00487 32543851
155 Madkhali O.A. A comprehensive review on potential applications of metallic nanoparticles as antifungal therapies to combat human fungal diseases Saudi Pharm. J. 31 2023 101733 10.1016/j.jsps.2023.101733
156 Cruz-Luna A.R. Cruz-Martínez H. Vásquez-López A. Medina D.I. Metal nanoparticles as novel antifungal agents for sustainable agriculture: current advances and future directions J. Fungi 7 2021 1033 10.3390/jof7121033
157 Alharbi N.S. Alsubhi N.S. Felimban A.I. Green synthesis of silver nanoparticles using medicinal plants: characterization and application J. Radiat. Res. Appl. Sci. 15 2022 1687 8507 10.1016/j.jrras.2022.06.012
158 Saeed Al-Zahrani S. Mohammed Al-Garni S. Antifungal potentiality of mycogenic silver nanoparticles capped with chitosan produced by endophytic Amesia atrobrunnea Saudi J. Biol. Sci. 30 2023 103746 10.1016/J.SJBS.2023.103746
159 Mosa M.A. El-Abeid S.E. Chitosan-loaded copper oxide nanoparticles: a promising antifungal nanocomposite against Fusarium wilt disease of tomato plants Sustain. Times 15 2023 14295 10.3390/SU151914295
160 Ngoc U.T.P. Nguyen D.H. Synergistic antifungal effect of fungicide and chitosan-silver nanoparticles on Neoscytalidium dimidiatum Green Process. Synth. 7 2018 132 138 10.1515/GPS-2016-0206/MACHINEREADABLECITATION/RIS
161 Lopez-Lima D. Mtz-Enriquez A.I. Carrión G. Basurto-Cereceda S. Pariona N. The bifunctional role of copper nanoparticles in tomato: effective treatment for Fusarium wilt and plant growth promoter Sci. Hortic. (Amsterdam) 277 2021 109810 10.1016/J.SCIENTA.2020.109810
162 Van Viet P. Nguyen H.T. Cao T.M. Van Hieu L. Fusarium antifungal activities of copper nanoparticles synthesized by a chemical reduction method J. Nanomater. 1 2016 1957612 10.1155/2016/1957612
163 Ntow-Boahene W. Cook D. Good L. Antifungal polymeric materials and nanocomposites Front. Bioeng. Biotechnol. 9 2021 1 14 10.3389/fbioe.2021.780328
164 Subbiah S. Ramesh M. Ashokan A.P. Narayanasamy A. Acute and sublethal toxicity of an azole fungicide tebuconazole on ionic regulation and Na +/K +-ATPase activity in a freshwater fish Cirrhinus mrigala ∼ 361 ∼ Int. J. Fish. Aquat. Stud. 8 2020 361 371 http://www.fisheriesjournal.com
165 Monapathi M.E. Oguegbulu J.C. Adogo L. Klink M. Okoli B. Mtunzi F. Modise J.S. Pharmaceutical pollution: azole antifungal drugs and resistance of opportunistic pathogenic yeasts in wastewater and environmental water Appl. Environ. Soil Sci. 1 2021 9985398 10.1155/2021/9985398
166 Tleuova A.B. Wielogorska E. Talluri V.S.S.L.P. Štěpánek F. Elliott C.T. Grigoriev D.O. Recent advances and remaining barriers to producing novel formulations of fungicides for safe and sustainable agriculture J. Control. Release. 326 2020 468 481 10.1016/j.jconrel.2020.07.035 32721524
167 Singh R.P. Handa R. Manchanda G. Nanoparticles in sustainable agriculture: an emerging opportunity J. Control. Release. 329 2021 1234 1248 10.1016/j.jconrel.2020.10.051 33122001
168 Liu R. Li J. Zhang L. Feng T. Zhang Z. Zhang B. Fungicide difenoconazole induced biochemical and developmental toxicity in wheat (Triticum aestivum l.) Plants 10 2021 1 15 10.3390/plants10112304
169 Gao S. Jiang J. Li X. Ye F. Fu Y. Zhao L. An environmentally safe formulation with enhanced solubility and fungicidal activity: self-assembly and characterization of Difenoconazole-β-CD inclusion complex J. Mol. Liq. 327 2021 114874 10.1016/j.molliq.2020.114874
170 Ahmad I. Farheen M. Kukreti A. Afzal O. Akhter M.H. Chitme H. Visht S. Altamimi A.S.A. Alossaimi M.A. Alsulami E.R. Jaremko M. Emwas A.H. Natural oils enhance the topical delivery of ketoconazole by nanoemulgel for fungal infections ACS Omega 8 2023 28233 28248 10.1021/acsomega.3c01571 37576685
171 Wanyika H. Sustained release of fungicide metalaxyl by mesoporous silica nanospheres Nanotechnology for Sustainable Development J. Nanoparticle Res. 15 2013 321 329 10.1007/s11051-013-1831-y
172 Farhana N. Aljafree A. Ahmad M.F. Aziz U.A. Bor M.Y. Jaafar A.M. Asib N. Nguyen H.L. Ibrahim M. Tahir M. Alif M. Latif M. Cordova K.E. Basyaruddin M. Rahman A. Calcium L -Malate and D -Tartarate Frameworks as Adjuvants for the Sustain- Able Delivery of Fungicide 2023
173 Yao J. Cui B. Zhao X. Wang Y. Zeng Z. Sun C. Yang D. Liu G. Gao J. Cui H. Preparation, characterization, and evaluation of azoxystrobin nanosuspension produced by wet media milling Appl. Nanosci. 8 2018 297 307 10.1007/s13204-018-0745-5
174 Xiao D. Wu H. Zhang Y. Kang J. Dong A. Liang W. Advances in stimuli-responsive systems for pesticides delivery: recent efforts and future outlook J. Control. Release. 352 2022 288 312 10.1016/j.jconrel.2022.10.028 36273530
175 Algahtani M.S. Ahmad M.Z. Ahmad J. Investigation of factors influencing formation of nanoemulsion by spontaneous emulsification: impact on droplet size, polydispersity index, and stability Bioengineering 9 2022 384 10.3390/BIOENGINEERING9080384/S1 36004909
176 Hassanzadeh H. Alizadeh M. Hassanzadeh R. Ghanbarzadeh B. Garlic essential oil-based nanoemulsion carrier: release and stability kinetics of volatile components Food Sci. Nutr. 10 2022 1613 1625 10.1002/FSN3.2784 35592277
177 Sun H. Ma Y. Huang X. Song L. Guo H. Sun X. Li N. Qiao M. Stabilization of flaxseed oil nanoemulsions based on flaxseed gum: effects of temperature, pH and NaCl on stability LWT 176 2023 114512 10.1016/J.LWT.2023.114512
178 Asmawi A.A. Salim N. Ngan C.L. Ahmad H. Abdulmalek E. Mas Masarudin J. Basyaruddin M. Rahman A. Excipient selection and aerodynamic characterization of nebulized lipid-based nanoemulsion loaded with docetaxel for lung cancer treatment Drug Deliv. Transl. Res. 2018 1 12 10.1007/s13346-018-0526-4 28849577
179 McClements D.J. Jafari S.M. Improving emulsion formation, stability and performance using mixed emulsifiers: a review Adv. Colloid Interface Sci. 251 2018 55 79 10.1016/j.cis.2017.12.001 29248154
180 Chang Y. McClements D.J. Optimization of orange oil nanoemulsion formation by isothermal low-energy methods: influence of the oil phase, surfactant, and temperature J. Agric. Food Chem. 62 2014 2306 2312 10.1021/jf500160y 24564878
181 An Y. Yan X. Li B. Li Y. Microencapsulation of capsanthin by self-emulsifying nanoemulsions and stability evaluation Eur. Food Res. Technol. 239 2014 1077 1085 10.1007/s00217-014-2328-3
182 Patra J.K. Das G. Fraceto L.F. Campos E.V.R. Rodriguez-Torres M.D.P. Acosta-Torres L.S. Diaz-Torres L.A. Grillo R. Swamy M.K. Sharma S. Habtemariam S. Shin H.S. Nano based drug delivery systems: recent developments and future prospects J. Nanobiotechnology 161 16 2018 1 33 10.1186/S12951-018-0392-8 2018
183 Elsawy M.A. Kim K.H. Park J.W. Deep A. Hydrolytic degradation of polylactic acid (PLA) and its composites Renew. Sustain. Energy Rev. 79 2017 1346 1352 10.1016/j.rser.2017.05.143
184 Sharma S.K. Shrivastava N. Rossi F. Tung L.D. Thanh N.T.K. Nanoparticles-based magnetic and photo induced hyperthermia for cancer treatment Nano Today 29 2019 100795 10.1016/j.nantod.2019.100795
185 Abramov A. Maiti B. Keridou I. Puiggalí J. Reiser O. Díaz D.D. A pH-triggered polymer degradation or drug delivery system by light-mediated cis/trans isomerization of o-hydroxy cinnamates Macromol. Rapid Commun. 42 2021 1 6 10.1002/marc.202100213
