Polymeric Nanocapsules as an Innovative Strategy against Fungal Infections: State of the Art and Perspectives in the One Health Context

Oliveira, Simone de Santana de; Silva, Danielle Luiza Santos da; Andrade, Diego Fontana de

doi:10.1590/1678-4324-2026250817

Abstract

The development of polymeric nanocapsules as antifungal delivery systems has gained attention due to the increasing incidence of fungal infections, such as candidiasis, often complicated by drug resistance and the limited efficacy of topical treatments. This integrative review analyzed 30 studies published between 2016 and 2025, retrieved from Scopus, Web of Science, and PubMed, including original research with in vitro and/or in vivo evaluations. The formulations contained antifungal agents such as nystatin, clotrimazole, fluconazole, itraconazole, ketoconazole, and essential oils, using polymers like chitosan, Eudragit^®, and polylactone derivatives. Nanoprecipitation was the most frequently employed preparation method. In vitro studies commonly evaluated antifungal activity, cytotoxicity, and permeation. Polymeric nanocapsules enhanced cutaneous and vaginal penetration of antifungal agents, improving efficacy against Candida spp., Aspergillus spp., and dermatophytes while minimizing systemic side effects. These nanocarriers represent a promising, sustainable, and interdisciplinary strategy for managing fungal and other infectious diseases within the One Health framework. Although most studies remain at the experimental stage, polymeric nanocapsules demonstrate significant potential for future clinical application, supporting their further investigation through safety and efficacy trials in human, animal, and environmental health contexts.

Keywords:
Polymeric nanocapsules; antifungal; integrative review; drug delivery systems; One Health.

HIGHLIGHTS

Polymeric nanocapsules enhance antifungal activity and reduce resistance.

Potential applications extend to human, animal, and environmental health (One Health).

Nanotechnology enables safe, innovative, and sustainable antifungal therapies.

INTRODUCTION

Fungal infections (mycoses) constitute an increasingly significant global health concern, affecting millions of individuals annually and imposing considerable clinical and socioeconomic burdens. These conditions, resulting from the proliferation of pathogenic fungi, encompass a wide spectrum of manifestations, from superficial infections, such as vulvovaginal candidiasis, onychomycosis, and dermatophytosis, to invasive and life-threatening systemic diseases, including aspergillosis and candidemia [¹,²]. The rising incidence of fungal infections, coupled with the emergence of antifungal resistance, underscores the urgent need for the development of novel, effective, and safe therapeutic alternatives [², ³, ⁴].

Despite the availability of conventional antifungal agents such as nystatin, fluconazole, clotrimazole, and itraconazole, their clinical performance remains suboptimal. Limitations related to poor solubility, chemical instability, rapid systemic clearance, and dose-dependent toxicity often compromise treatment efficacy [¹,³,⁵,⁶,⁷]. Furthermore, the limited bioavailability and local retention of topical formulations, alongside the growing resistance of Candida spp., Aspergillus spp., and dermatophytes, exacerbate therapeutic challenges and highlight the need for innovative drug delivery approaches [⁴,⁵,⁶,⁷,⁸,⁹,¹⁰].

In this context, nanotechnology-based systems, particularly polymeric nanocapsules, have emerged as a promising and versatile platform for antifungal drug delivery. These carriers enable efficient encapsulation of active pharmaceutical ingredients, controlled and sustained release profiles, improved solubility, and targeted delivery to infection sites, thereby enhancing therapeutic efficacy while minimizing systemic adverse effects [⁹,¹⁰]. When incorporated into biocompatible matrices such as hydrogels or mucoadhesive films, nanocapsules can further optimize drug penetration across cutaneous and mucosal barriers, prolong drug residence time at the site of action, and ultimately increase antifungal effectiveness [¹¹, ¹², ¹³,¹⁴].

Various polymers, including chitosan, Eudragit^®, and polylactone derivatives, have been extensively investigated for nanocapsule production. These materials are often associated with natural bioactives, essential oils, or antioxidant additives to modulate physicochemical and biopharmaceutical properties such as mucoadhesion, permeability, and stability [¹⁴, ¹⁵, ¹⁶]. The growing body of literature over the past decade reflects a marked increase in scientific interest in antifungal nanocarriers, primarily driven by the global need to overcome microbial resistance and optimize topical and systemic antifungal therapies.

Importantly, recent advances in nanotechnology have expanded the application of antifungal nanocapsules beyond the confines of human medicine, aligning their use with the integrative principles of the One Health approach. This conceptual framework recognizes the inextricable interdependence between human, animal, and environmental health, emphasizing that the mitigation of infectious diseases and antimicrobial resistance requires cross-sectoral and sustainable strategies [⁶,¹¹,¹⁶,¹⁷,¹⁸]. Within this perspective, the rational design and deployment of nanocarrier-based antifungal systems emerge as key elements for promoting global health security.

In veterinary medicine, nanotechnology has been successfully explored to enhance therapeutic efficacy while reducing reliance on conventional antimicrobials. For instance, polymeric and metallic nanoparticles such as those based on silver, copper, or gold have shown promising outcomes in the treatment of bovine mastitis, offering safer and more effective therapeutic alternatives and contributing to the control of antimicrobial resistance in livestock production systems [¹⁹,²⁰]. Similarly, in the agricultural sector, nanoscale formulations of fungicides, herbicides, and plant growth regulators have revolutionized crop protection practices. Biodegradable polymeric nanocapsules loaded with essential oils such as thymol, eugenol, or citronella have demonstrated potent antifungal activity against phytopathogenic species including Fusarium, Botrytis, and Alternaria, while simultaneously reducing environmental contamination and preserving soil microbiota [³,¹⁶,²¹,²²,²³,²⁴].

Taken together, these interdisciplinary applications illustrate the translational potential of antifungal nanocapsules as sustainable health technologies. By bridging pharmaceutical innovation with ecological responsibility, nanotechnology-based antifungal strategies embody the essence of the One Health paradigm, addressing the intertwined challenges of microbial resistance, therapeutic inefficacy, and environmental impact. Consequently, the pursuit of new antifungal therapies is not solely a biomedical endeavor but also an ethical and ecological imperative in the context of planetary health.

Nevertheless, despite substantial scientific progress, critical gaps remain regarding the standardization of formulation characterization, efficacy testing, and comparative clinical validation. These limitations highlight the need for comprehensive and integrative reviews capable of consolidating existing knowledge, identifying research gaps, and guiding future directions in antifungal nanotechnology.

Accordingly, the present integrative review aims to compile and critically analyze the current state of the art in antifungal nanocapsules, emphasizing the composition, preparation methodologies, biological in vitro and in vivo outcomes, as well as the analytical approaches employed for their assessment. Furthermore, this review addresses the current challenges and emerging perspectives across human, animal, and plant health within the One Health framework, thereby contributing to a comprehensive understanding of the role of nanotechnology in the future of antifungal therapy.

MATERIAL AND METHODS

This integrative review was conducted following the methodological framework adapted from Souza [²⁵] and de Andrade [²⁶]. The review was guided by the following research question: “What polymeric nanocapsule formulations have been described in the scientific literature with potential applications in human, animal, and/or environmental health?”

The literature search was performed based on this guiding question, and all retrieved studies were screened according to predefined inclusion and exclusion criteria. Data collection was performed on August 23, 2025, using the electronic databases PubMed, Scopus, and Web of Science. The search strategy applied was (“nanocapsule*” AND “antifungal”).

The inclusion criteria comprised original research articles published between 2016 and 2025 that employed in vitro and/or in vivo experimental models. Studies were excluded if they were review articles, did not involve nanocapsule-based formulations, lacked an antifungal focus, were duplicate records, or had no full-text availability.

The selected articles were analyzed, and key information was categorized according to the composition of the polymeric nanocapsules, including polymer/oil combinations and incorporated active ingredient (active pharmaceutical ingredient or active substance), the preparation methods used, and the in vitro and in vivo techniques applied to assess antifungal activity. This categorization allows to identify the main raw materials and active compounds, the most commonly used preparation methods, the experimental protocols adopted to evaluate the formulations, the fungal strains shown to be susceptible, and the principal outcomes reported.

RESULTS

Study Identification and Selection

The search process retrieved a total of 340 articles across the three databases. Duplicate removal resulted in 199 unique articles, which were subjected to manual screening. This step led to the exclusion of studies that did not meet the initial scope, leaving 96 articles for further evaluation. After applying the predefined eligibility criteria, a final set of 30 studies was selected for analysis (Figure 1). The included studies comprised in vitro and/or in vivo experimental models, addressing the development and characterization of nanocapsule formulations with antifungal applications. These findings provide an updated overview of the strategies explored in the last decade and highlight the growing interest in nanotechnology-based antifungal therapies.

Figure 1
Flow diagram of study selection for the integrative review.

The composition of the polymeric nanocapsules (including the polymer, oil, and active pharmaceutical ingredient) along with the preparation methods employed and the in vitro and in vivo antifungal activity assessment techniques used in the studies included in this review, are summarized in Table 1.

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Table 1
Composition of polymeric nanocapsules, including polymer, oil, and active pharmaceutical ingredient, along with the preparation methods and in vitro and in vivo antifungal activity assessment techniques reported in the studies included in this integrative review.

Furthermore, to visually summarize the compiled data from the studies included in this review, Figure 2 presents an overview of research on polymeric nanocapsules for fungal infections using a four-level Sankey diagram. This diagram illustrates the relationships between the polymer used, the active pharmaceutical ingredient (API) or active ingredient, the target fungal microorganism, and the primary biological outcome (fungistatic or fungicidal).

Figure 2
Four-level Sankey diagram illustrating the relationships among polymers, active pharmaceutical ingredients (APIs)/active ingredients, target fungal microorganisms, and biological outcomes (fungistatic or fungicidal) in studies involving polymeric nanocapsules. The abbreviations used in the figure are as follows: EO (Essential Oil); PCL (Polycaprolactone); PMMA (Poly(methyl methacrylate)); PEG (Polyethylene glycol); PLGA (Poly(lactide-co-glycolide)); ASSP (Acetylated Sterculia striata polysaccharide); PSSP (Propionylated Sterculia striata polysaccharide); CS-CA (Chitosan-cinnamic acid conjugate); and 6CN10 (2-[(4-nitrobenzylidene)amino]-4,5,6,7-tetrahydro-4H-benzo[b]thiophene-3-carbonitrile).Antifungal-Loaded Polymeric Nanocapsule Research from a One Health Perspective

Figure 3 shows the distribution of the studies included in this review according to the intended application of the formulations, based on a One Health perspective. Most of the polymeric nanocapsule formulations reported in the literature were developed for the treatment of human diseases (83%), followed by those intended for agricultural use (13%). Only one formulation was described as targeting an agent with zoonotic potential, indicating its possible application in both human and animal health contexts.

Figure 3
Distribution of studies included in the review according to the intended application of the formulations, based on the One Health perspective.

Composition and Preparation Methods of Antifungal-Loaded Polymeric Nanocapsules

The nanocapsules with antifungal properties included in this review typically consist of an oily core surrounded by a biodegradable polymeric shell, which controls the release of the active pharmaceutical ingredient and protects it from degradation. Figure 4 illustrates the distribution of polymers used in the production of polymeric nanocapsules across the studies included in this review. The most employed polymers include chitosan, Eudragit^® RS100, and polylactone derivatives (PCL, PLA), widely used due to their biocompatibility, stability, and ability to provide sustained drug release.

Figure 4
Distribution of polymers used in the production of polymeric nanocapsules. “Others” category comprises polymers that appeared only once, such as: PMMA, PEG, Gum Tragacanth, Cellulose acetate, Sterculia striata acetylated polysaccharide (ASSP), Sterculia striata polysaccharide (PSSP), Carboxymethyl cellulose (CMC), Soy lecithin, Lignin, Grape seed tannins, poly(D-lactide), and Chitosan chemically modified (CS-CA). The abbreviations used in the figure are as follows: PCL (Polycaprolactone) and PLGA (Poly(lactide-co-glycolide)).

Figure 5 summarizes the distribution of APIs/active ingredients incorporated into polymeric nanocapsule formulations across the studies included in this review. The presence of an oil core allows the incorporation of hydrophobic drugs such as nystatin, clotrimazole, itraconazole, fluconazole, and ketoconazole, as well as bioactive essential oils, including eugenol, chamomile, cinnamon, pistacia, which act synergistically, enhancing both the antifungal spectrum and antioxidant potential [¹,²,⁶,²²,²⁴,³⁵,³⁷]. These structural features are critical for the therapeutic performance of the formulations, as they influence the penetration, retention, and controlled release of the active agent in cutaneous and mucosal tissues [¹,³,⁶].

Figure 5
Distribution of APIs/active ingredients loaded into polymeric nanocapsules formulations. “Others” category comprises APIs/active ingredients that appeared only once: Aloe Vera extract, Amiodarone, Azulene, Bisabolol, Chamomile essential oil, Chloramphenicol, Chromolaena odorata essential oil, Ciclopirox, Dapsone, Glycerol monolaurate, Grape seed tannins, Itraconazole, Ketoconazole, Lignin, Linalool, Methyl cinnamate, Neem oil, Nystatin, Peppermint essential oil, Pistacia atlantica subsp. kurdica (PAHEO) essential oil, Propolis, Syzygium aromaticum essential oil, Terbinafine hydrochloride, Thymol, Tioconazole, Zinc phenyl-thio-phthalocyanine, and 6CN10 (specific organic compound). EO means essential oil.

The preparation of antifungal nanocapsules involved various methods, including nanoemulsification and nanoprecipitation [¹,³,⁶,¹⁰]. The choice of method directly influenced particle size, distribution, surface charge, encapsulation efficiency and controlled release of the antifungal agent. For instant, nanoprecipitation and interfacial polymerization were employed to obtain uniform and stable particles capable of penetrating biofilms and providing sustained drug release [¹,²,³,³⁹].

In systems containing essential oils or other lipophilic compounds, encapsulation within polymeric nanocapsules protected the active substances from degradation and volatilization, thereby maintaining their antifungal activity over time [²,⁶,²²,²⁴]. In some studies, spray drying or lyophilization was subsequently employed to enhance long-term stability and facilitate handling, converting liquid dispersions into solid formulations while preserving the nanostructural properties until final application [¹⁰,²⁴].

The selection of polymers, surfactants and excipients also played a critical role, promoting mucoadhesion, tissue permeation and controlled release which are essential for the observed therapeutic efficacy in both in vitro and in vivo assays [⁶,⁷,¹⁴,²⁹]. Therefore, the preparation methodology not only defined the physicochemical characteristics of the nanocapsules but also determined their functional performance and safety profile.

Characterization and Evaluation of the Antifungal Activity of Polymeric Nanocapsules

The characterization and evaluation of polymeric nanocapsules are fundamental steps in the development of nanostructured systems, as they allow the correlation of physicochemical and structural properties with therapeutic performance.

Parameters such as particle size and distribution, surface charge, polymer composition and encapsulation efficiency directly influence the controlled drug release, penetration into biofilms and tissues, stability and antifungal efficacy [¹,²,⁶,¹⁰,²⁹]. Therefore, well-structure evaluation methods are essential to optimize formulations, ensuring that specific structural characteristic translate into superior functional outcomes in vitro and in vivo, while also providing therapeutic safety and predictability.

In vitro evaluation

Physicochemical characterization, including analyses of particle size, polydispersity index, zeta potential and encapsulation efficiency was widely used to ensure colloidal stability, bioavailability and controlled drug release [²,⁶,⁷,¹⁰,¹⁸]. Controlled release was evaluated through diffusion assays using synthetic membranes or biological models, demonstrating that nanoencapsulation prolongs the availability of the active agent and minimizes local concentration fluctuations, resulting in a sustained therapeutic effect [¹,⁷,¹⁰,²⁹]. In systems containing essential oils or antioxidant compounds, this approach ensured the maintenance of antifungal activity over time [²,³,⁶,¹⁰,²¹,²⁴,²⁷].

Most studies evaluating the antifungal activity of polymeric nanocapsules utilized fungal growth assays, including microdilution, agar diffusion, and biofilm inhibition tests, to assess their efficacy against Candida species [¹,³,⁵,⁷,¹⁰,¹¹,¹²,¹³,¹⁴,²³,²⁸,²⁹,³¹,³³,³⁵], Aspergillus spp. [⁴,¹⁵], and dermatophytes [⁶,³⁸]. These assays allowed determination of the minimum inhibitory concentration (MIC) and assessment of biofilm control, demonstrating that nanoencapsulation substantially enhances antifungal activity compared to conventional formulations [¹,³, ²⁸,³⁵,³⁹].

In vivo evaluation

Animal infection models, including vulvovaginal candidiasis, fungal keratitis and chronic wounds co-infected with bacteria and fungi were used to assess real therapeutic efficacy, tissue penetration and duration of antifungal action [¹⁴,²³,³⁹].

Mucoadhesive hydrogels containing diphenyl diselenide nanocapsules showed enhanced antifungal activity in vulvovaginal candidiasis models when compared to non-encapsulate formulations [¹⁴]. Chitosan-guar gum nanocapsules loaded with nystatin demonstrated effective fungal control and simulated healing in experimental keratitis models [³⁹]. Similarly, thermoreversible gels and mucoadhesive films containing clotrimazole exhibited sustained release and improved in vivo antifungal efficacy [⁷,¹¹].

Toxicity assays, including histological, hematological and cytotoxicity analyses were primarily performed on formulations containing essential oils or bioactive compounds, confirming the safety and tolerability of the nanocapsules [²,⁶,¹¹,²¹,²⁴].

Evaluation of synergic effects

Beyond direct antifungal activity, some studies explored synergistic and multifunctional effects such as antioxidant and anti-inflammatory actions, which complement antifungal activity and contribute to tissue healing or food preservation [²¹,²³,²⁴,³³]. Polymeric nanocapsules containing essential oils or phenolic compounds, when combined with conventional drugs, demonstrated significant synergism, increasing efficacy against resistant species [⁶,⁸,¹⁰,¹⁵,¹⁸,²²,²⁴,²⁷,³¹,³⁵,³⁷]. Furthermore, nanocapsulated systems applied to food and agricultural products such as those containing Pistacia atlantica and Cananga odorata extracts showed preservative and in situ antifungal efficacy, reinforcing the versatility of nanostructured systems [²²,²⁴].

DISCUSSION

Polymeric nanocapsules have the potential to simultaneously benefit human, animal, plant, and environmental health, aligning with an expanded One Health perspective that recognizes the interdependence among these systems. By improving therapeutic efficacy, reducing the need for repeated antifungal treatments, and minimizing residual drug release into soil and water, nanocapsule-based strategies may mitigate cross-species transmission risks, reduce environmental contamination, and support healthier agroecosystems.

The studies included in this review reveal a clear pattern in the selection of polymers for nanocapsules production, where biodegradable synthetic polymers and cationic natural polymers are employed according to specific pharmaceutical and biological objectives. Polyesters such as PLGA and PCL are recurrent choices when controlled biodegradability, protection of lipophilic active pharmaceutical ingredients (APIs), and sustained release are required properties that favor physicochemical stability and prolongation of therapeutic effect [³⁵,³⁷,³⁸]. In parallel, chitosan and its cationic derivatives are widely reported because of their mucoadhesive properties, intrinsic antimicrobial activity, and ability to interact with biological surfaces (skin, vaginal mucosa, nail bed), which justifies their use as coatings and in formulations for topical and vaginal administration [⁴,⁶,¹⁵,¹⁸,²⁴,³⁷]. Natural acetylated polymers (e.g., Sterculia striata and lignin) also emerge as alternatives that add biodegradability and antioxidant protection to the carrier system [²¹,²⁴,³¹].

Polymeric coating strategies have been used for multiple and complementary purposes: formation of a cationic layer (frequently chitosan or functionalized chitosan) provides a positive surface charge that improves interaction with fungal cells and membranes and increases mucoadhesion, while also acting as a diffusional barrier to modulate API release and protect the lipid/polymeric core from degradation and aggregation during storage [⁶,²²]. Eudragit^®-based coatings and other amphiphilic polymers have also been applied to modulate release or confer resistance to specific gastric or dermal conditions when relevant [⁷,¹¹].

Regarding active ingredients, the literature includes both classical antifungals used in clinical practice such as nystatin, clotrimazole, itraconazole, fluconazole, ketoconazole, terbinafine, tioconazole, ciclopirox, and amphotericin B, and non-conventional compounds (amiodarone, eugenol, neem oil, plant extracts, glycerol monolaurate) [¹,³,⁹,¹⁰,¹¹,¹⁷,¹⁸,²²,²⁹,³¹,³⁹]. Selection of nanocapsules components follows three predominant criteria: (i) solubility profile: many APIs are lipophilic and therefore benefit from oily cores or polymeric matrices to increase solubility and stability [¹,¹³,¹⁴,²⁹,³¹]; (ii) clinical need: particularly for formulations designed to overcome resistance, for example, strategies targeting fluconazole-resistant strains, where nanocarriers can improve intracellular drug delivery [³,⁹,¹¹,³⁴,³⁸]; and (iii) application target: which determines the polymer/excipient choice (for instance, nail formulations require excipients that favor penetration into the nail bed) [⁷,¹⁷,²²-²⁴].

In summary, the pairing of active ingredients and matrix is guided by the physicochemical properties of the active compound and the intended route or therapeutic indication [¹,³,⁷,⁹,¹¹,¹³,¹⁴,¹⁷,²²-²⁴,²⁹,³¹,³⁴,³⁸]. Essential oils (for example, eugenol, neem oil, chamomile oil) are used both as active antifungal agents and as internal phases that improve solubilization of lipophilic drugs. Their inclusion is justified by documented antifungal activity, potential synergy with conventional antifungals (leading to MIC reduction), the ability to modulate dermal/ungual permeation, and antioxidant effects that enhance the stability of oxidation-sensitive formulations [⁶,²²,²³,³⁰,³⁵,³⁶,³⁷,³⁸]. Essentially, these oils broaden the activity spectrum and enable multifunctional approaches (antifungal effect + permeation enhancement + antioxidant protection).

With regard to preparation methods, the diversity observed reflects the variety of matrices and formulation goals. Nanoprecipitation (solvent displacement/interfacial deposition) is widely reported for its simplicity, reproducibility, and ability to produce particles with narrow size distribution, and it is frequently used in polymeric formulations for incorporating lipophilic drugs [¹⁰,¹⁵,¹⁷,²³,³⁰,³¹,³²,³⁵,³⁸]. For specific dosage forms (e.g., vaginal films, nail lacquers), film-forming and controlled-drying techniques have been adapted to incorporate nanocapsules into polymeric film matrices [⁷,¹⁴,¹⁷]. The conversion of liquid dispersions into solid or semi-solid forms plays a central role in pharmaceutical translation. Identified strategies include incorporation into hydrogels (Carbopol^®, gellan gum, Pemulen/Pullulan, blends with chitosan) to obtain semi-solid formulations with increased local residence time and mucoadhesion (relevant for vaginal and topical routes) [¹,⁶,¹⁴]. For solid forms, spray-drying and lyophilization are commonly adopted: spray-drying has been described as a method that yields dry powders with good reproducibility and controlled release, convenient for handling and transport, while lyophilization better preserves the integrity of sensitive nanocapsules but requires cryoprotectants and entails higher operational costs [²⁹].

The formulations evaluated are predominantly intended for treatment of human fungal infections, such as vulvovaginitis, cutaneous candidiasis, onychomycosis, and fungal keratitis, with emphasis on topical, vaginal, and ungual delivery [¹,⁶,¹⁵]. In vitro and in vivo studies have shown that encapsulating classical antifungals in nanocapsules improves pharmacodynamic parameters: reduction of MIC, increased local residence time, reduced required dosing, and potential reversal of resistance, especially evident in lipid-core nanoparticle strategies against fluconazole-resistant strains [¹,³,¹¹,¹⁴,³⁴]. It is important to emphasize that, despite the existence of experimental animal model studies (e.g., experimental keratitis [³⁹] or murine models [¹⁴,³⁴]), there is a shortage of studies directed to clinical veterinary practice, i.e., routine therapeutic applications in dogs and cats with naturally acquired mycoses, which represents a relevant translational gap in the One Health context.

For agricultural applications, several studies have evaluated nanocarriers containing essential oils, tannins, lignin, and plant extracts against phytopathogenic fungi. The active ingredients most frequently used were Syzygium cumini extract [⁸], eugenol and other phenolics [¹⁰,¹⁸,³⁸] and cinnamon oils [³⁰] and neem oil [³⁶]. Experimental protocols included in vitro mycelial growth inhibition assays such as agar dilution [²⁹,³⁷], broth microdilution [⁹,¹⁴,³¹], and disk diffusion [⁷,¹⁰,³⁰]. In addition, in situ and in vivo tests were performed to assess antifungal efficacy under controlled conditions [¹,²²,²³,³⁴].

The phytopathogens investigated encompassed Verticillium dahliae, Phaeomoniella chlamydospora, Phaeoacremonium minimum and other agriculturally relevant fungi [²¹]. Encapsulation consistently enhanced stability (by reducing volatility and photodegradation), promoted controlled release, and improved bioavailability of the bioactive compounds, leading to superior antifungal efficacy compared with free compounds. These findings support the potential of nanoformulations as sustainable alternatives to synthetic fungicides, combining efficiency with lower environmental impact [¹²,¹⁵,¹⁶,²²].

The application of polymeric nanocapsules in agriculture also emerges as a strategic response to the growing need for sustainable antifungal strategies. Conventional fungicides, although effective, are often limited by environmental persistence, phytotoxicity, and the development of resistant fungal strains. Nanostructured systems can offer controlled and prolonged release of active agents, reducing the frequency of applications and minimizing the environmental chemical load. Encapsulation of natural compounds, such as essential oils, protects them from degradation by light or oxidation, increasing their stability and effectiveness under field conditions. These systems can also limit leaching and toxicity to non-target organisms, contributing to environmental safety and the preservation of beneficial microorganisms.

The studies included in this review highlights methodological advances and promising applications for both human health and crop protection but also identifies important translational gaps. In particular, the lack of studies focused on animal health, considering the high prevalence of dermatophytoses in companion animals and their zoonotic potential, constitutes a critical limitation that hinders full integration of nanotechnological solutions into the One Health paradigm [²⁰].

Although no formulations have been developed exclusively for veterinary fungal infections, a recent study proposed a formulation with potential applications in both human and animal health, targeting infections caused by Trichophyton mentagrophytes, a pathogenic dermatophyte responsible for a variety of superficial infections in humans and animals [³⁸]. The study evaluated the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of human and animal isolates of T. mentagrophytes against eugenol, eugenol-loaded nanocapsules (nano-eugenol), and itraconazole. The findings demonstrated the potential of polymeric nanocapsules for veterinary applications and highlighted the feasibility of extending these nanostructures to animal health, despite the limited number of studies currently available.

Polymeric nanocapsules can simultaneously benefit human and animal health by enhancing drug efficacy and reducing the adverse effects commonly associated with conventional treatments [⁴⁰]. Their advantages over traditional formulations derive from their ability to optimize drug performance, leading to superior therapeutic outcomes [⁴⁰,⁴¹]. In production and companion animals, this improved efficacy directly contributes to food safety and, in cases of fungal zoonoses, provides greater protection to pet owners and communities by enabling faster and more effective treatments [⁴²].

Moreover, the enhanced solubility, stability, and absorption of encapsulated drugs result in more favorable clinical outcomes, reducing fungal burden and lowering the risk of zoonotic transmission to pet owners and agricultural workers [³⁸]. In food-producing species, increased therapeutic efficiency at lower doses decreases the presence of pharmaceutical residues in animal-derived products, thereby reinforcing food safety [⁴³, ⁴⁴, ⁴⁵, ⁴⁶]. Additionally, because nanocapsules require smaller overall amounts of drug, they reduce the environmental impact associated with veterinary pharmaceutical waste, strengthening the interconnectedness of animal, human, and environmental health envisioned within the One Health framework.

In this context, the contribution of nanocapsules to One Health is further exemplified by their capacity for controlled drug release, a feature with significant environmental implications [⁴⁷,⁴⁸]. Controlled release supports gradual and targeted delivery of the active ingredient, minimizing overdosing and potentially reducing the amount of pharmaceutical residue entering soil and water, an important contrast to the rapid metabolization and excretion typical of conventional drugs [52]. By lowering the chemical load in ecosystems, polymeric nanocapsule-based technologies contribute to mitigating aquatic and terrestrial pollution and reducing the emergence of antimicrobial resistance, thereby reinforcing their environmental relevance [⁴⁹, ⁵⁰].

Despite these benefits, the rapid expansion of nanomaterial applications raises important concerns. Nanoparticles, particularly those produced through top-down methods, exhibit high reactivity due to their large surface area and can penetrate small organisms, potentially leading to cumulative toxic effects. Thus, the growing nanoindustry urgently requires comprehensive ecotoxicological assessments of nanomaterial fate and persistence to ensure that these technological advances do not emerge as new environmental pollutants [⁵¹].

This review presents limitations and challenges that should be considered when interpreting its findings. First, the applied time restriction (2016-2025) may have excluded relevant earlier evidence, as the development and application of polymeric nanocapsules predate this period. In addition, the current evidence base shows substantial heterogeneity in formulation methods, including variations in polymer types, surfactants, and preparation parameters, which complicates direct comparisons across studies. Another important limitation arises from the absence of standardized protocols for physicochemical characterization and antifungal activity, covering both in vitro and in vivo approaches. Moreover, despite promising in vitro findings, in vivo studies remain scarce, and a clear translational gap persists between experimental research and clinical or veterinary application. Among the selected studies, only five included in vivo experiments using murine models or post-harvest food testing, while all others relied exclusively on in vitro analyses [¹,¹⁴,²²,²³,³⁴]. Notably, none of the identified studies reported data from clinical trials in either humans or animals, highlighting a substantial gap in the translation of these formulations to real-world medical or veterinary use. This scenario underscores the need for well-designed clinical investigations to validate the efficacy, safety, and applicability of polymeric nanocapsules under actual infection conditions.

These limitations represent major barriers to the clinical translation of polymeric nanocapsules as a strategy against fungal infections, particularly the lack of standardized characterization protocols, the scarcity of in vivo and clinical data, and existing regulatory challenges. Additionally, environmental and sustainability considerations, such as polymer biodegradability and potential ecotoxicity, remain insufficiently explored. To advance the field, future studies should prioritize scalable formulations of polymeric nanocapsules, the standardization of characterization methods for quality control, the expansion of in vivo and clinical evaluations, and the incorporation of environmental safety assessments that consider the materials used in nanocapsules production. These efforts will enhance reproducibility, support regulatory approval, and enable eventual clinical implementation. Addressing these methodological inconsistencies, expanding in vivo investigations, and aligning nanotechnology research with regulatory and translational requirements will be essential for enabling the development of clinically relevant polymeric nanocapsule-based antifungal therapies.

Recent advances in polymeric nanocapsule-based antifungal systems reveal promising opportunities for safer, more effective, and environmentally responsible applications. Natural and synthetic polymers, such as carboxymethylcellulose [¹⁸], lignin [²¹], and tannin-based materials [²¹], combined with plant-derived bioactive compounds have demonstrated enhanced stability, improved bioavailability, and controlled-release behavior, contributing to more efficient antifungal action with reduced ecological impact. Additionally, the incorporation of essential oils into polymeric nanocapsules provides synergistic effects, enabling multifunctional formulations suitable for human and veterinary medicine as well as for plant protection in agricultural systems [⁶,¹²,²³,³⁰,³⁸].

Looking ahead, future efforts should focus on optimizing formulation parameters to achieve sustained release, improving physicochemical stability, and evaluating antifungal performance in more complex biological, environmental, and agricultural models. Integrating nanotechnology development with principles of sustainability, biodegradability, and environmental safety will be essential for designing multifunctional antifungal platforms that address the interconnected health of humans, animals, plants, and ecosystems. Advancing these strategies strengthens the comprehensive One Health framework, fostering integrated and innovative solutions aligned with current global health and environmental challenges.

CONCLUSION

In summary, polymeric nanocapsule systems based on natural or synthetic polymers, combined with plant-derived bioactive compounds or conventional antifungal drugs, show strong antifungal potential, improved stability, and established applications in human health and agricultural crop protection. However, the limited number of studies involving veterinary species highlights a significant gap, particularly for mycoses with zoonotic potential, where advances could strengthen the One Health approach.

These technologies offer promising opportunities for innovative, safe, and sustainable antifungal strategies that integrate human, animal, and environmental health needs. To advance the field, future studies should prioritize scalable nanocapsule formulations, standardized characterization methods, expanded in vivo and clinical evaluations, and environmental safety assessments that consider material composition. Addressing these aspects will improve reproducibility, support regulatory approval, and enable clinical and practical implementation while ensuring that biodegradability and potential ecotoxicity are adequately evaluated.

Funding:
This research was funded by CNPq/Brazil (Grant #406629/2023-4), FAPERGS/Brazil and the National Institute of Science and Technology in 3D Printing and Advanced Materials Applied to Human and Veterinary Health - INCT_3D-Saúde (Grant #406436/2022-3).
Institutional Review Board Statement:
Not applicable.
Informed Consent Statement:
Not applicable.

Acknowledgments:

The authors gratefully acknowledge the institutional support provided by the Graduate Program in Pharmaceutical Sciences of the Federal University of Rio Grande do Sul (UFRGS) and the CAPES Periodicals Portal for granting access to the scientific literature consulted in this study.

Use of Generative Artificial Intelligence

The authors declare that large language models and other generative artificial intelligence (AI) or AI-assisted technologies cannot be credited as authors and have not been listed as authors of this paper.

The authors declare that generative artificial intelligence (AI) or AI-assisted tools were used under full human supervision. The tool(s) and version(s) used, and their purpose, are described here: English language revision and grammar correction. No confidential or sensitive data were uploaded to such tool(s), and all AI-assisted content was checked, corrected and approved by the authors, who take full responsibility for the integrity and originality of the manuscript.

Data Availability Statement:

Research data are available in the body of the manuscript.

REFERENCES

¹ AbouSamra MM, Basha M, Awad GEA, Mansy SS. A promising nystatin nanocapsular hydrogel as an antifungal polymeric carrier for the treatment of topical candidiasis. J Drug Deliv Sci Technol. 2019;49:365-74.
² Calvo NL, Sreekumar S, Svetaz LA, Lamas MC, Moerschbacher BM, Leonardi D. Design and characterization of chitosan nanoformulations for the delivery of antifungal agents. Int J Mol Sci [Internet]. 2019 [cited 2026 Jan 25];20(15):3686. Available from: https://doi.org/10.3390/ijms20153686
» https://doi.org/10.3390/ijms20153686
³ Bianchin MD, Borowicz SM, Machado GDM, Pippie B, Guterres SS, Pohlmann AR, et al. Lipid core nanoparticles as a broad strategy to reverse fluconazole resistance in multiple Candida species. Colloids Surf B Biointerfaces. 2019;175:523-9.
⁴ Cé R, Marchi JG, Bergamo VZ, Fuentefria AM, Lavayen V, Guterres SS, et al. Chitosan-coated dapsone-loaded lipid-core nanocapsules: growth inhibition of clinical isolates, multidrug-resistant Staphylococcus aureus and Aspergillus spp. Colloids Surf A Physicochem Eng Asp. 2016;511:153-61.
⁵ Assis DN, Araújo RS, Fuscaldi LL, Fernandes SOA, Mosqueira VCF, Cardoso VN. Biodistribution of free and encapsulated 99mTc-fluconazole in an infection model induced by Candida albicans Biomed Pharmacother. 2018;99:438-44.
⁶ Carvalho SYB, Almeida RR, Pinto NAR, Mayrinck C, Vieira SS, Haddad JF, et al. Encapsulation of essential oils using cinnamic acid grafted chitosan nanogel: preparation, characterization and antifungal activity. Int J Biol Macromol. 2021;166:902-12.
⁷ Cervi VF, Saccol CP, Rosa Pinheiro T, Santos RCV, Sari MHM, Cruz L. A novel nanotechnological mucoadhesive and fast-dissolving film for vaginal delivery of clotrimazole: design, characterization, and in vitro antifungal action]. Drug Deliv Transl Res. 2022;12(12):2907-19.
⁸ Bitencourt PER, Ferreira LM, Cargnelutti LO, Denardi L, Boligon A, Fleck M, et al. A new biodegradable polymeric nanoparticle formulation containing Syzygium cumini: phytochemical profile, antioxidant and antifungal activity and in vivo toxicity. Ind Crops Prod. 2016;83:400-7.
⁹ Santos FL, Zilles JC, Machado AU, Marques MS, Costa BS, Kulkamp Guerreiro IC, et al. Polymeric nanocapsules containing ozonated oil and terbinafine hydrochloride as a potential treatment against dermatophytes. AAPS Pharm. Sci. Tech. 2023;24(7):198.
¹⁰ Dubey P, Kumar A, Vaiphei KK, Basrani S, Jadhav A, Wilen CE, et al. A poly-δ-decalactone (PDL) based nanoemulgel for topical delivery of ketoconazole and eugenol against Candida albicans Nanoscale Adv. 2024 Aug 2;6(21):5322-36.
¹¹ Englert V, Verdi M, Vianna Santos R, Cruz L, Sari MHM. Diphenyl diselenide and clotrimazole co-loaded into Eudragit RS 100 nanocapsules formulation has superior antioxidant potential and promising anti-Candida activity. Braz Arch Biol Technol. 2020;63:e2020200087.
¹² Kumar A, Kujur A, Singh PP, Prakash B. Nanoencapsulated plant-based bioactive formulation against food-borne molds and aflatoxin B1 contamination: preparation, characterization and stability evaluation in the food system. Food Chem. 2019;287:139-50.
¹³ Evangelista RP, Amantino CF, Pietro RCLR, Sorrechia R, Piazza RD, Marques RFC, et al. Copolymer-nanocapsules of zinc phenyl-thio-phthalocyanine and amphotericin B associated with antimicrobial photodynamic therapy against Candida albicans. Photodiagnosis Photodyn Ther. 2021;34:102273.
¹⁴ Zimmermann ES, Ferreira LM, Denardi LB, Sari MHM, Cervi VF, Nogueira CW, et al. Mucoadhesive gellan gum hydrogel containing diphenyl diselenide-loaded nanocapsules presents improved anti-Candida action in a mouse model of vulvovaginal candidiasis. Eur J Pharm Sci. 2021;167:106011.
¹⁵ Cortés-Higareda M, Ramos-García MD, Correa-Pacheco ZN, Del Río-García JC, Bautista-Baños S. Nanostructured chitosan/propolis formulations: characterization and effect on the growth of Aspergillus flavus and production of aflatoxins. Heliyon. 2019;5(5):e01642.
¹⁶ Alghuthaymi MA, Rajkuberan C, Rajiv P, Kalia A, Bhardwaj K, Bhardwaj P, et al. Nanohybrid antifungals for control of plant diseases: current status and future perspectives. J Fungi. 2021;7(1):48.
¹⁷ Gaballah EY, Borg TM, Mohamed EA. Hydroxypropyl chitosan nail lacquer of ciclopirox-PLGA nanocapsules for augmented in vitro nail plate absorption and onychomycosis treatment. Int J Nanomedicine. 2023;18:59-76.
¹⁸ Jacumazo J, Carvalho MM, Parchen GP, Campos IMF, Ballesteros Garcia MJ, Brugnari T, et al. Development, characterization and antimicrobial activity of sodium dodecyl sulfate-polysaccharides capsules containing eugenol. Carbohydr Polym. 2020;230:115562.
¹⁹ Prakash V, Rathaur A, Rai DC, Singh SJ. Role of nanotechnology in mastitis treatment for dairy cows: a mini review. Lett Anim Biol. 2023;2(2):29-34.
²⁰ Tocco I, Zavan B, Bassetto F, Vindigni V. Nanotechnology-based therapies for skin wound regeneration. J Nanomater. 2012;2012:714134.
²¹ Falsini S, Nieri T, Schiff S, Papini A, Salvatici MC, Carella G, et al. Enhancing the Efficacy of Natural Repellents Against Grapevine Pathogens by Tannins-Lignin-Mixed Nanovectors]. BioNanoScience. 2024;14(1):474-84.
²² Hesami G, Darvishi S, Zarei M, Hadidi M. [Fabrication of chitosan nanoparticles incorporated with Pistacia atlantica subsp. kurdica hulls essential oil as a potential antifungal preservative against strawberry grey mould. Int J Food Sci Technol. 2021;56(9):4215-33.
²³ Kalita S, Kandimalla R, Devi B, Kalita B, Kalita K, Deka M, et al. Dual delivery of chloramphenicol and essential oil by poly-ɛ-caprolactone-Pluronic nanocapsules to treat MRSA-Candida co-infected chronic burn wounds. RSC Adv. 2017;7(3):1749-58.
²⁴ Upadhyay N, Singh VK, Dwivedy AK, Chaudhari AK, Dubey NK. Assessment of nanoencapsulated Cananga odorata essential oil in chitosan nanopolymer as a green approach to boost the antifungal, antioxidant and in situ efficacy. Int J Biol Macromol. 2021;171:480-90.
²⁵ Souza MT, Silva MD, Carvalho R. [Integrative review: what is it? How to do it?]. Einstein (São Paulo). 2010 Mar;8(1):102-6.
²⁶ Andrade DF, Gewehr JLH, de Almeida EA. Safety and Efficacy of the Therapeutic Use of Cannabis-Based Products in the Treatment of Dogs: An Integrative Review. Cannabis Cannabinoid Res. 2022 Dec 1;7(6):736-44.
²⁷ Ghayempour S, Montazer M, Mahmoudi Rad M. Encapsulation of Aloe Vera extract into natural Tragacanth Gum as a novel green wound healing product. Int J Biol Macromol. 2016;93:344-9.
²⁸ Lopes LQ, Santos CG, Vaucher RA, Raffin RP, Santos RC. Nanocapsules with glycerol monolaurate: Effects on Candida albicans biofilms. Microb Pathog. 2016 Aug;97:119-24.
²⁹ Ribeiro RF, Motta MH, Härter APG, Flores FC, Beck RCR, Schaffazick SR, et al. Spray-dried powders improve the controlled release of antifungal tioconazole-loaded polymeric nanocapsules compared with lyophilized products. Mater Sci Eng C Mater Biol Appl. 2016;59:875-84.
³⁰ Liakos IL, Iordache F, Carzino R, Scarpellini A, Oneto M, Bianchini P, et al. Cellulose acetate - essential oil nanocapsules with antimicrobial activity for biomedical applications. Colloids Surf B Biointerfaces. 2018;172:471-9.
³¹ Matoso Sombra F, Richter AR, de Araújo AR, de Oliveira Silva Ribeiro F, de Fátima Souza Mendes J, dos Santos Fontenelle RO, et al. Nanocapsules of Sterculia striata acetylated polysaccharide as a potential monomeric amphotericin B delivery matrix. Int J Biol Macromol. 2019;130:655-63.
³² Neves WW, Neves RP, Macêdo DPC, de Araújo Eleamen GR, de Moura Kretzschmar EA, Oliveira EE, et al. Incorporation of 2-amino-thiophene derivative in nanoparticles: enhancement of antifungal activity. Braz J Microbiol. 2020;51(2):647-55.
³³ Sombra FM, Richter AR, de Araújo AR, de Oliveira Silva Ribeiro F, Souza Mendes JF, dos Santos Fontenelle RO, et al. Development of amphotericin B-loaded propionate Sterculia striata polysaccharide nanocarrier. Int J Biol Macromol. 2020;146:1133-41.
³⁴ Oliveira NK, Frank LA, Squizani ED, Reuwsaat JCV, Marques BM, Motta H, et al. New nanotechnological formulation based on amiodarone-loaded lipid core nanocapsules displays anticryptococcal effect. Eur J Pharm Sci. 2021;162:105816.
³⁵ Rosato R, Napoli E, Granata G, Di Vito M, Garzoli S, Geraci C, et al. Study of the chemical profile and antifungal activity against Candida auris of Cinnamomum cassia essential oil and of its nano-formulations based on polycaprolactone. Plants (Basel). 2023;12(2):358.
³⁶ Pasquoto-Stigliani T, Campos EVR, Oliveira JL, Silva CMG, Bilesky-José N, Guilger M, et al. Nanocapsules Containing Neem (Azadirachta Indica) Oil: Development, Characterization, And Toxicity Evaluation. Sci Rep. 2017 Jul 19;7(1):5929.
³⁷ Liu T, Qu X, Zhao M, Zhang D, Guo J. Investigation of the production and antifungal properties of nanocapsules containing chamomile essential oil. Sci Rep. 2025;15(1):23981.
³⁸ Malakootikhah J, Sharifzadeh A, Rastegar M, Khosravi A, Nikaein D. Synergistic Antifungal Efficacy of Eugenol-Loaded Nanocapsules Combined With Itraconazole Against Trichophyton mentagrophytes. Vet Med Sci. 2025;11(3):e70352.
³⁹ Kumar V, Mohan P, Rajeswari J, Antoniraj MG, Kesavan K. Healing efficiency of nystatin-loaded chitosan-guar gum-based nanocapsules in experimental fungal keratitis. Int J Biol Macromol. 2025;322:146979.
⁴⁰ Ianiski LB, Rodrigues FS, Stibbe PC, Weiblen C, Pereira DIB, Santurio JM, et al. [Nanotechnology in veterinary medicine: a review]. Cienc Rural [Internet]. 2022 [cited 2026 Jan 25];52(6). Available from: https://www.scielo.br/j/cr/a/s9Mc4NZ8pkfrYRrRDhDZ4fy/?format=pdf⟨=en
» https://www.scielo.br/j/cr/a/s9Mc4NZ8pkfrYRrRDhDZ4fy/?format=pdf⟨=en
⁴¹ Müller RH, Radtke M, Wissing SA. [Nanostructured lipid matrices for improved microencapsulation of drugs. Int J Pharm. 2002;242(1-2):121-8.
⁴² Şenel S. Nanotechnology and Animal Health. Pharm Nanotechnol. 2021;9(1):26-35.
⁴³ Alizadeh Z, Mohebali M, Aghabarari B, Zarei Z, Hassanpour G, Eskandari SE, et al. Formulation, in vitro evaluation and therapeutic effect of chitosan coated pluronic F127 micelles containing miltefosine for the treatment of visceral leishmaniasis in domestic dogs naturally infected by Leishmania infantum Res Vet Sci. 2025;182:105467.
⁴⁴ Türkmen E, Parmaksız S, Nigiz E, Sağıroğlu M, Şenel S. A safe bioadhesive system for topical delivery of combined antimicrobials in treatment of skin infections in veterinary medicine. J Drug Deliv Sci Technol. 2023;80:104116.
⁴⁵ Go H, Yeon KD, Lee JH, Ahn SY, Nam A. Disseminated fungal infection with Aspergillus versicolor and Schizophyllum commune in a dog. Med Mycol Case Rep. 2022;38:25-9.
⁴⁶ Lazo REL, Alves FMS, Domingos EL, Cobre AF, Farago PV, Cruz L, et al. Advances in soft nanoparticle-based platforms for human and veterinary trichomoniasis therapy: A scoping review. Eur J Pharm Biopharm. 2025;208:114638.
⁴⁷ Ramadan AA, Hamdallah SI, Mahdy DM, Barakat HS, El-Khordagui LK. Eco-friendly lipid nanocapsules for drug delivery: Promises and challenges. Matter. 2025;8(8):102362.
⁴⁸ Frank LA, Contri RV, Beck RCR, Pohlmann AR, Guterres SS. Improving drug biological effects by encapsulation into polymeric nanocapsules. WIREs Nanomed Nanobiotechnol. 2015;7(5):623-39.
⁴⁹ Tian H, Tang Z, Zhuang X, Chen X, Jing X. Biodegradable synthetic polymers: Preparation, functionalization and biomedical application. Prog Polym Sci. 2012;37(2):237-80.
⁵⁰ Fernández-Pérez M. Controlled release systems to prevent the agro-environmental pollution derived from pesticide use. J Environ Sci Health B. 2007 Sep-Oct;42(7):857-62.
⁵¹ Luhach V, Yadav J, Barala P, Sangwan P, Suhag S, Hooda V. The future of herbicide application: controlled-release formulations for enhanced agricultural sustainability. Des Monomers Polym. 2025;28(1):24-43.

Editor-in-Chief:
Paulo Vitor Farago

Associate Editor:
Paulo Vitor Farago

Publication Dates

Publication in this collection
12 June 2026
Date of issue
2026

History

Received
28 Oct 2025
Accepted
06 Dec 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

[1] ¹ AbouSamra MM, Basha M, Awad GEA, Mansy SS. A promising nystatin nanocapsular hydrogel as an antifungal polymeric carrier for the treatment of topical candidiasis. J Drug Deliv Sci Technol. 2019;49:365-74.

[2] ² Calvo NL, Sreekumar S, Svetaz LA, Lamas MC, Moerschbacher BM, Leonardi D. Design and characterization of chitosan nanoformulations for the delivery of antifungal agents. Int J Mol Sci [Internet]. 2019 [cited 2026 Jan 25];20(15):3686. Available from: https://doi.org/10.3390/ijms20153686
» https://doi.org/10.3390/ijms20153686

[3] ³ Bianchin MD, Borowicz SM, Machado GDM, Pippie B, Guterres SS, Pohlmann AR, et al. Lipid core nanoparticles as a broad strategy to reverse fluconazole resistance in multiple Candida species. Colloids Surf B Biointerfaces. 2019;175:523-9.

[4] ⁴ Cé R, Marchi JG, Bergamo VZ, Fuentefria AM, Lavayen V, Guterres SS, et al. Chitosan-coated dapsone-loaded lipid-core nanocapsules: growth inhibition of clinical isolates, multidrug-resistant Staphylococcus aureus and Aspergillus spp. Colloids Surf A Physicochem Eng Asp. 2016;511:153-61.

[5] ⁵ Assis DN, Araújo RS, Fuscaldi LL, Fernandes SOA, Mosqueira VCF, Cardoso VN. Biodistribution of free and encapsulated 99mTc-fluconazole in an infection model induced by Candida albicans Biomed Pharmacother. 2018;99:438-44.

[6] ⁶ Carvalho SYB, Almeida RR, Pinto NAR, Mayrinck C, Vieira SS, Haddad JF, et al. Encapsulation of essential oils using cinnamic acid grafted chitosan nanogel: preparation, characterization and antifungal activity. Int J Biol Macromol. 2021;166:902-12.

[7] ⁷ Cervi VF, Saccol CP, Rosa Pinheiro T, Santos RCV, Sari MHM, Cruz L. A novel nanotechnological mucoadhesive and fast-dissolving film for vaginal delivery of clotrimazole: design, characterization, and in vitro antifungal action]. Drug Deliv Transl Res. 2022;12(12):2907-19.

[8] ⁸ Bitencourt PER, Ferreira LM, Cargnelutti LO, Denardi L, Boligon A, Fleck M, et al. A new biodegradable polymeric nanoparticle formulation containing Syzygium cumini: phytochemical profile, antioxidant and antifungal activity and in vivo toxicity. Ind Crops Prod. 2016;83:400-7.

[9] ⁹ Santos FL, Zilles JC, Machado AU, Marques MS, Costa BS, Kulkamp Guerreiro IC, et al. Polymeric nanocapsules containing ozonated oil and terbinafine hydrochloride as a potential treatment against dermatophytes. AAPS Pharm. Sci. Tech. 2023;24(7):198.

[10] ¹⁰ Dubey P, Kumar A, Vaiphei KK, Basrani S, Jadhav A, Wilen CE, et al. A poly-δ-decalactone (PDL) based nanoemulgel for topical delivery of ketoconazole and eugenol against Candida albicans Nanoscale Adv. 2024 Aug 2;6(21):5322-36.

[11] ¹¹ Englert V, Verdi M, Vianna Santos R, Cruz L, Sari MHM. Diphenyl diselenide and clotrimazole co-loaded into Eudragit RS 100 nanocapsules formulation has superior antioxidant potential and promising anti-Candida activity. Braz Arch Biol Technol. 2020;63:e2020200087.

[12] ¹² Kumar A, Kujur A, Singh PP, Prakash B. Nanoencapsulated plant-based bioactive formulation against food-borne molds and aflatoxin B1 contamination: preparation, characterization and stability evaluation in the food system. Food Chem. 2019;287:139-50.

[13] ¹³ Evangelista RP, Amantino CF, Pietro RCLR, Sorrechia R, Piazza RD, Marques RFC, et al. Copolymer-nanocapsules of zinc phenyl-thio-phthalocyanine and amphotericin B associated with antimicrobial photodynamic therapy against Candida albicans. Photodiagnosis Photodyn Ther. 2021;34:102273.

[14] ¹⁴ Zimmermann ES, Ferreira LM, Denardi LB, Sari MHM, Cervi VF, Nogueira CW, et al. Mucoadhesive gellan gum hydrogel containing diphenyl diselenide-loaded nanocapsules presents improved anti-Candida action in a mouse model of vulvovaginal candidiasis. Eur J Pharm Sci. 2021;167:106011.

[15] ¹⁵ Cortés-Higareda M, Ramos-García MD, Correa-Pacheco ZN, Del Río-García JC, Bautista-Baños S. Nanostructured chitosan/propolis formulations: characterization and effect on the growth of Aspergillus flavus and production of aflatoxins. Heliyon. 2019;5(5):e01642.

[16] ¹⁶ Alghuthaymi MA, Rajkuberan C, Rajiv P, Kalia A, Bhardwaj K, Bhardwaj P, et al. Nanohybrid antifungals for control of plant diseases: current status and future perspectives. J Fungi. 2021;7(1):48.

[17] ¹⁷ Gaballah EY, Borg TM, Mohamed EA. Hydroxypropyl chitosan nail lacquer of ciclopirox-PLGA nanocapsules for augmented in vitro nail plate absorption and onychomycosis treatment. Int J Nanomedicine. 2023;18:59-76.

[18] ¹⁸ Jacumazo J, Carvalho MM, Parchen GP, Campos IMF, Ballesteros Garcia MJ, Brugnari T, et al. Development, characterization and antimicrobial activity of sodium dodecyl sulfate-polysaccharides capsules containing eugenol. Carbohydr Polym. 2020;230:115562.

[19] ¹⁹ Prakash V, Rathaur A, Rai DC, Singh SJ. Role of nanotechnology in mastitis treatment for dairy cows: a mini review. Lett Anim Biol. 2023;2(2):29-34.

[20] ²⁰ Tocco I, Zavan B, Bassetto F, Vindigni V. Nanotechnology-based therapies for skin wound regeneration. J Nanomater. 2012;2012:714134.

[21] ²¹ Falsini S, Nieri T, Schiff S, Papini A, Salvatici MC, Carella G, et al. Enhancing the Efficacy of Natural Repellents Against Grapevine Pathogens by Tannins-Lignin-Mixed Nanovectors]. BioNanoScience. 2024;14(1):474-84.

[22] ²² Hesami G, Darvishi S, Zarei M, Hadidi M. [Fabrication of chitosan nanoparticles incorporated with Pistacia atlantica subsp. kurdica hulls essential oil as a potential antifungal preservative against strawberry grey mould. Int J Food Sci Technol. 2021;56(9):4215-33.

[23] ²³ Kalita S, Kandimalla R, Devi B, Kalita B, Kalita K, Deka M, et al. Dual delivery of chloramphenicol and essential oil by poly-ɛ-caprolactone-Pluronic nanocapsules to treat MRSA-Candida co-infected chronic burn wounds. RSC Adv. 2017;7(3):1749-58.

[24] ²⁴ Upadhyay N, Singh VK, Dwivedy AK, Chaudhari AK, Dubey NK. Assessment of nanoencapsulated Cananga odorata essential oil in chitosan nanopolymer as a green approach to boost the antifungal, antioxidant and in situ efficacy. Int J Biol Macromol. 2021;171:480-90.

[25] ²⁵ Souza MT, Silva MD, Carvalho R. [Integrative review: what is it? How to do it?]. Einstein (São Paulo). 2010 Mar;8(1):102-6.

[26] ²⁶ Andrade DF, Gewehr JLH, de Almeida EA. Safety and Efficacy of the Therapeutic Use of Cannabis-Based Products in the Treatment of Dogs: An Integrative Review. Cannabis Cannabinoid Res. 2022 Dec 1;7(6):736-44.

[27] ²⁷ Ghayempour S, Montazer M, Mahmoudi Rad M. Encapsulation of Aloe Vera extract into natural Tragacanth Gum as a novel green wound healing product. Int J Biol Macromol. 2016;93:344-9.

[28] ²⁸ Lopes LQ, Santos CG, Vaucher RA, Raffin RP, Santos RC. Nanocapsules with glycerol monolaurate: Effects on Candida albicans biofilms. Microb Pathog. 2016 Aug;97:119-24.

[29] ²⁹ Ribeiro RF, Motta MH, Härter APG, Flores FC, Beck RCR, Schaffazick SR, et al. Spray-dried powders improve the controlled release of antifungal tioconazole-loaded polymeric nanocapsules compared with lyophilized products. Mater Sci Eng C Mater Biol Appl. 2016;59:875-84.

[30] ³⁰ Liakos IL, Iordache F, Carzino R, Scarpellini A, Oneto M, Bianchini P, et al. Cellulose acetate - essential oil nanocapsules with antimicrobial activity for biomedical applications. Colloids Surf B Biointerfaces. 2018;172:471-9.

[31] ³¹ Matoso Sombra F, Richter AR, de Araújo AR, de Oliveira Silva Ribeiro F, de Fátima Souza Mendes J, dos Santos Fontenelle RO, et al. Nanocapsules of Sterculia striata acetylated polysaccharide as a potential monomeric amphotericin B delivery matrix. Int J Biol Macromol. 2019;130:655-63.

[32] ³² Neves WW, Neves RP, Macêdo DPC, de Araújo Eleamen GR, de Moura Kretzschmar EA, Oliveira EE, et al. Incorporation of 2-amino-thiophene derivative in nanoparticles: enhancement of antifungal activity. Braz J Microbiol. 2020;51(2):647-55.

[33] ³³ Sombra FM, Richter AR, de Araújo AR, de Oliveira Silva Ribeiro F, Souza Mendes JF, dos Santos Fontenelle RO, et al. Development of amphotericin B-loaded propionate Sterculia striata polysaccharide nanocarrier. Int J Biol Macromol. 2020;146:1133-41.

[34] ³⁴ Oliveira NK, Frank LA, Squizani ED, Reuwsaat JCV, Marques BM, Motta H, et al. New nanotechnological formulation based on amiodarone-loaded lipid core nanocapsules displays anticryptococcal effect. Eur J Pharm Sci. 2021;162:105816.

[35] ³⁵ Rosato R, Napoli E, Granata G, Di Vito M, Garzoli S, Geraci C, et al. Study of the chemical profile and antifungal activity against Candida auris of Cinnamomum cassia essential oil and of its nano-formulations based on polycaprolactone. Plants (Basel). 2023;12(2):358.

[36] ³⁶ Pasquoto-Stigliani T, Campos EVR, Oliveira JL, Silva CMG, Bilesky-José N, Guilger M, et al. Nanocapsules Containing Neem (Azadirachta Indica) Oil: Development, Characterization, And Toxicity Evaluation. Sci Rep. 2017 Jul 19;7(1):5929.

[37] ³⁷ Liu T, Qu X, Zhao M, Zhang D, Guo J. Investigation of the production and antifungal properties of nanocapsules containing chamomile essential oil. Sci Rep. 2025;15(1):23981.

[38] ³⁸ Malakootikhah J, Sharifzadeh A, Rastegar M, Khosravi A, Nikaein D. Synergistic Antifungal Efficacy of Eugenol-Loaded Nanocapsules Combined With Itraconazole Against Trichophyton mentagrophytes. Vet Med Sci. 2025;11(3):e70352.

[39] ³⁹ Kumar V, Mohan P, Rajeswari J, Antoniraj MG, Kesavan K. Healing efficiency of nystatin-loaded chitosan-guar gum-based nanocapsules in experimental fungal keratitis. Int J Biol Macromol. 2025;322:146979.

[40] ⁴⁰ Ianiski LB, Rodrigues FS, Stibbe PC, Weiblen C, Pereira DIB, Santurio JM, et al. [Nanotechnology in veterinary medicine: a review]. Cienc Rural [Internet]. 2022 [cited 2026 Jan 25];52(6). Available from: https://www.scielo.br/j/cr/a/s9Mc4NZ8pkfrYRrRDhDZ4fy/?format=pdf⟨=en
» https://www.scielo.br/j/cr/a/s9Mc4NZ8pkfrYRrRDhDZ4fy/?format=pdf⟨=en

[41] ⁴¹ Müller RH, Radtke M, Wissing SA. [Nanostructured lipid matrices for improved microencapsulation of drugs. Int J Pharm. 2002;242(1-2):121-8.

[42] ⁴² Şenel S. Nanotechnology and Animal Health. Pharm Nanotechnol. 2021;9(1):26-35.

[43] ⁴³ Alizadeh Z, Mohebali M, Aghabarari B, Zarei Z, Hassanpour G, Eskandari SE, et al. Formulation, in vitro evaluation and therapeutic effect of chitosan coated pluronic F127 micelles containing miltefosine for the treatment of visceral leishmaniasis in domestic dogs naturally infected by Leishmania infantum Res Vet Sci. 2025;182:105467.

[44] ⁴⁴ Türkmen E, Parmaksız S, Nigiz E, Sağıroğlu M, Şenel S. A safe bioadhesive system for topical delivery of combined antimicrobials in treatment of skin infections in veterinary medicine. J Drug Deliv Sci Technol. 2023;80:104116.

[45] ⁴⁵ Go H, Yeon KD, Lee JH, Ahn SY, Nam A. Disseminated fungal infection with Aspergillus versicolor and Schizophyllum commune in a dog. Med Mycol Case Rep. 2022;38:25-9.

[46] ⁴⁶ Lazo REL, Alves FMS, Domingos EL, Cobre AF, Farago PV, Cruz L, et al. Advances in soft nanoparticle-based platforms for human and veterinary trichomoniasis therapy: A scoping review. Eur J Pharm Biopharm. 2025;208:114638.

[47] ⁴⁷ Ramadan AA, Hamdallah SI, Mahdy DM, Barakat HS, El-Khordagui LK. Eco-friendly lipid nanocapsules for drug delivery: Promises and challenges. Matter. 2025;8(8):102362.

[48] ⁴⁸ Frank LA, Contri RV, Beck RCR, Pohlmann AR, Guterres SS. Improving drug biological effects by encapsulation into polymeric nanocapsules. WIREs Nanomed Nanobiotechnol. 2015;7(5):623-39.

[49] ⁴⁹ Tian H, Tang Z, Zhuang X, Chen X, Jing X. Biodegradable synthetic polymers: Preparation, functionalization and biomedical application. Prog Polym Sci. 2012;37(2):237-80.

[50] ⁵⁰ Fernández-Pérez M. Controlled release systems to prevent the agro-environmental pollution derived from pesticide use. J Environ Sci Health B. 2007 Sep-Oct;42(7):857-62.

[51] ⁵¹ Luhach V, Yadav J, Barala P, Sangwan P, Suhag S, Hooda V. The future of herbicide application: controlled-release formulations for enhanced agricultural sustainability. Des Monomers Polym. 2025;28(1):24-43.

Composition (Polymer/oil)	API/Active ingredient	Preparation method	Method for assessing antifungal activity	Reference
Gum Tragacanth / Almond oil	Aloe Vera extract	Nanoemulsification	Shake flask method with Candida albicans	[²⁷]
Polymeric blend PMMA and PEG / Caprylic/Capric Triglycerides	Glycerol monolaurate	Nanoprecipitation	In vitro: growth, MIC, biofilm formation and biofilm prevention using Candida albicans ATCC 14053.	[²⁸]
PCL / Medium chain triglycerides	Tioconazole	Interfacial deposition of preformed polymer	In vitro: agar diffusion against Candida albicans.	[²⁹]
PCL and Chitosan/ Medium chain triglycerides (caprylic/capric)	Dapsone	Interfacial deposition of preformed polymer	In vitro: antifungal activity against 6 isolates of Aspergillus spp. (A. fumigatus, A. flavus, A. niger), including ATCC 16888 by MIC and MIA (minimum inhibitory area of the nanocapsules) determination	[⁴]
PCL / Lemongrass essential oil	Chloramphenicol and lemongrass essential oil	Nanoprecipitation	In vitro: MIC/MFC against Candida spp., biofilm, time-kill assays; In vivo: (animal model - Swiss albino mice): burn wounds infected with MRSA + Candida albicans.	[²³]
Cellulose acetate / Essential oils (peppermint, cinnamon, lemongrass)	Essential oils (peppermint, cinnamon, lemongrass)	Nanoprecipitation	In vitro: MIC and disk diffusion of Candida albicans	[³⁰]
Chitosan / glycerol and canola oil	propolis	Nanoprecipitation	Mycelial growth, conidial germination and aflatoxin production against Aspergillus flavus	[¹⁵]
PCL / caprylic/capric triglyceride + sorbitan monostearate	Fluconazole	Interfacial deposition of preformed polymer	In vitro: antifungal susceptibility assays (MIC, MFC) in resistant clinical isolates of Candida spp.	[³]
Sterculia striata acetylated polysaccharide (ASSP) / Miglyol 812^®	Amphotericin B	Nanoprecipitation	In vitro: broth microdilution assay (CLSI M27-A3) to determine MIC against Candida albicans (ATCC and clinical isolates).	[³¹]
Chitosan / mixture of Thymol, Methyl cinnamate, Linalool	Thymol, Methyl cinnamate, Linalool	Interfacial deposition of preformed polymer	Antifungal activity against Aspergillus flavus and 10 other species of food fungi; inhibition of Aflatoxin B1 in Pennisetum glaucum seeds	[¹²]
PCL / Squalene	Nystatin	Nanoprecipitation	In vivo model of cutaneous infection by Candida albicans in rats	[¹]
PCL / medium-chain triglycerides	Diphenyl diselenide	Interfacial deposition of preformed polymer	In vitro: broth microdilution test against Candida albicans and C. glabrata; In vivo: murine model (Swiss mice) of vulvovaginal candidiasis infected with Candida albicans	[¹⁴]
Eudragit^® RS100 / Virgin coconut oil	Clotrimazol + diphenyl diselenide	Interfacial deposition of preformed polymer	In vitro: MIC against Candida albicans (ATCC 24433) and fluconazole-resistant Candida glabrata (clinical isolate)	[¹¹]
Chitosan and carboxymethyl cellulose / Eugenol	Eugenol	Polymer deposition	In vitro: MIC against Candida albicans, Aspergillus niger, Trichoderma sp. and Gliocladium sp.	[¹⁸]
PCL / Miglyol 812^®	6CN10 (2-[(4-nitrobenzilidene)-amino]-4,5,6,7-tetrahidro-4H-benzo[b]tiofeno-3-carbonitrila	Nanoprecipitation	In vitro: MIC and MF against clinical species of Candida and Cryptococcus. Formation and treatment of C. neoformans biofilm on silicone discs.	[³²]
Chitosan / Chromolaena odorata essential oil	Chromolaena odorata essential oil	Ionic gelation	In vitro: antifungal activity against Aspergillus flavus. In situ (food model): Peanut kernels (Arachis hypogaea) stored for 4 weeks, evaluation of fungal growth, AFB1 production.	[²⁴]
Sterculia striata polysaccharide modified by acylation with propionic anhydride (PSSP) / Miglyol 812^®	Amphotericin B	Nanoemulsification	MIC against 4 strains of Candida albicans (ATCC + clinical isolates).	[³³]
Chitosan with tripolyphosphate conjugation / Essential oil of Pistacia atlantica subsp. kurdica (PAHEO)	Essential oil of Pistacia atlantica subsp. kurdica (PAHEO)	Emulsification followed by ionic gelation	In vitro: Pour plate method with different concentrations; In vivo: Coating of strawberries inoculated with Botrytis cinerea	[²²]
PCL / caprylic/capric triglycerides	Amiodarone and fluconazole	Interfacial deposition of preformed polymer	In vitro: MIC, checkerboard, virulence phenotypes (C. neoformans); In vivo: murine model of cryptococcosis (intranasal infection, intraperitoneal or intranasal treatment)	[³⁴]
Eudragit^® RS100 / Pomegranate seed oil	Clotrimazole	Interfacial deposition of preformed polymer	In vitro: disk diffusion Candida albicans (ATCC 14,053)	[⁷]
PLGA and Soy lecithin / Soy oil	zinc phenyl-thio-phthalocyanine + Amphotericin B	Interfacial deposition of preformed polymer	In vitro: antimicrobial photodynamic therapy and minimum fungicidal concentration against Candida albicans (ATCC 90028)	[¹³]
Eudragit^® RS100 / Ozonated sunflower seed oil	Terbinafine hydrochloride	Interfacial deposition of preformed polymer	In vitro: Microdilution test and Time-kill assay in broth and against dermatophytes (Trichophyton rubrum, T. mentagrophytes, Nannizzia gypsea, Microsporum canis)	[⁹]
PLGA / Maisina (glyceryl monolinoleate)	Ciclopirox	Nanoprecipitation	In vitro: MIC and zone of inhibition; Ex vivo: Growth of Trichophyton rubrum in human nail fragments.	[¹⁷]
PCL / Cinnamomum cassia essential oil	Cinnamomum cassia essential oil	Interfacial deposition of preformed polymer	In vitro: Candida albicans ATCC 90028 and Candida auris (clinical strain CA10, biofilm producer) MIC, MFC, and biofilm eradication tests	[³⁵]
Lignin, grape seed tannins (biopolymers)	Lignin, grape seed tannins (biopolymers)	Emulsification	In vitro: antifungal assay against Verticillium dahliae, Phaeomoniella chlamydospora, Phaeoacremonium minimum; conidial germination assay.	[²¹]
poly(D-lactide) / Eugenol	Ketoconazole + Eugenol	Nanoprecipitation	In vitro: antifungal activity against Candida albicans ATCC 90028 by the disk diffusion assay	[¹⁰]
Chitosan chemically modified with cinnamic acid (CS-CA) / Essential oil of Syzygium aromaticum and Cinnamomum.	Essential oil of Syzygium aromaticum and Cinnamomum.	Nanoprecipitation	In vitro: antifungal activity against Microsporum canis by MIC and inhibition of mycelial growth	[⁶]
PCL / Neem oil + Oleic acid	Neem oil	Emulsification followed by solvent evaporation	In vitro: determination of MIC against Candida albicans	[³⁶]
Chitosan / Chamomile essential oil (Matricaria chamomilla), rich in bisabolol and azulene	Chamomile essential oil (Matricaria chamomilla), rich in bisabolol and azulene	Nanoemulsification	In vitro: agar diffusion with Candida albicans, Aspergillus fumigatus, Trichophyton rubrum, Epidermophyton floccosum	[³⁷]
PCL / Caprylic/capric triglycerides	Eugenol + Itraconazole	Nanoprecipitation	In vitro: determination of MIC, MFC and checkerboard assay against Trichophyton mentagrophytes isolated from humans and animals	[³⁸]