Trends in micro and nanoencapsulation of various plant-based bioactive compounds for enhanced biological activities: a review

1 Introduction

Bioactive substances, synonymous with secondary metabolites, are a group of phytochemicals found in plants that have potent medicinal properties. Medicinal plants contribute to a large number of novel bioactive compounds, and play a major role in the treatment of various disorders worldwide (Ho et al., 2018; Tanaka and Kashiwada, 2021) Numerous findings indicate that plant-based supplements provide greater protection against chronic diseases such as cardiovascular disease, cancer, and diabetes mellitus (Noore et al., 2021), and against some infectious diseases, viz. asthma, common cold, coronavirus disease, pneumonia (Khalid et al., 2022). Phytochemicals are largely plant secondary metabolites, and nutrients like minerals/vitamins that can exert pharmacological activity in significant quantities are frequently excluded from the classification (Pawase et al., 2024). Even the World Health Organization (WHO) report suggests that developing countries rely on these phytochemicals for primary health, wellness, and around 80% of the global population depends on these plant-based medicines (Holloway and Dijk, 2011; Noore et al., 2021). Numerous pharmacological properties of plant-based bioactive compounds have been reported, including anti-inflammatory, anti-hyperglycemic, antibacterial, antiproliferative, antioxidant, and anti-diabetic effects (Figure 1). During the past decade, the search for new bioactive compounds has intensified. Seeds, vegetables, nuts, leaves, fruits, legumes, and other plant parts contain a large number of bioactive phytochemicals (Al Juhaimi et al., 2018; Pachuau et al., 2021; 2019; Sagar et al., 2018; Septembre-Malaterre et al., 2018; Xiao and Bai, 2019). PubMed now has almost 5,000 publications for the phrase “natural products,” up from 452 in 2000. Furthermore, plants play a significant role in traditional medicine, cosmetics, as well as in homeopathy, even though their application extends far beyond novel drugs allowed by regulatory authorities such as the Brazilian Health Regulatory Agency (ANVISA) or the US Food and Drug Administration (FDA) (Makrani et al., 2025; Newman and Cragg, 2016).

Natural chemicals produced by plants account for around a quarter of all medications currently available in the market, either directly or indirectly (Calixto, 2019). The ability to synthesize chemical entities from medicinal plants has proven to be a crucial resource for the production of novel drugs (Atanasov et al., 2021). To achieve this aim, these newly developed bioactive compounds can be utilized as medicinal mediators for the development of novel analogs through higher efficacy and lower toxicity, and they can be used in a variety of ways (Atanasov et al., 2015). Commercially accessible plant-derived pharmaceutically active compounds include salicin (an analgesic drug), which was extracted from Salix spp., and its derivative, aspirin (Desborough and Keeling, 2017). Cinchona officinalis and Artemisia annua were used to isolate quinine, and artemisinin, as well as their antimalarial derivatives (Pandey and Pandey-Rai, 2016). Digoxin (a well-known cardiac glycoside) was discovered in Digitalis lanata and has been used for over 200 years (Virgadamo, 2015). The analgesics morphine and codeine were isolated from opium (Papaver somniferum) (Reed and Hudlicky, 2015). An antitumoral and antiviral substance called podophyllotoxin, accessed from Podophyllum peltatum, was structurally modified to screen biological activities (Jin et al., 2022). Alkaloids, ellagic acid, phytosterols, carotenoids, anthocyanins, morphine, flavonoids, and tocopherols, as well as zeaxanthin, coumarins, nicotine, xanthones, phenolic acids, and ellagitannins, are a few of the frequently discovered phytochemicals known for their bioactive potential (Figure 2).

Phytochemicals in fruits and vegetables, such as phenolics, may enhance their resistance to oxidation, as well as their taste, colour, flavour, and odour, in addition to their bioactivities (Naczk and Shahidi, 2006). Various conventional methods such as maceration, Soxhlet extraction, and hydrodistillation are employed for bioactive extraction depending on numerous factors including solvent used, plant matrix type, temperature and time. Although these traditional procedures have inherent drawbacks, such as the overuse of solvents and extremely lengthy processing times. Nowadays, “Green technologies” are in trend; these sustainable, innovative, chemical-free extraction processes with improved overall yield, such as enzyme-assisted, ultrasound-assisted, microwave-assisted, high-pressure processing, supercritical fluid-based, chemical-free, pulsed electric field-assisted, and pressurized liquid extraction processes are attracting researchers. Another technological hurdle is the further purification of the recovered bioactives because these phytochemicals have different molecular structures depending on their type, biological activity and source. Following extraction and purification, it is crucial to safeguard the recovered bioactive component because these bioactive compounds are extremely vulnerable to environmental exposure, includes high temperatures and moisture. In order to confirm whether biological activity of these compounds is maintainable until they reach and carry out their assigned task at the intended place inside human body, protection measures like encapsulation are required.

Encapsulation is essential for preventing the degradation of bioactive compounds and improving their functional performance. It involves enclosing an active substance within a thin coating, which may be solid, liquid, or gaseous in nature. Depending on the size of the coated particles, the process is classified as micro- or nano-encapsulation. This approach isolates the core material using a protective layer, typically composed of polymers, thereby preserving its integrity while enabling additional functionalities such as flavour masking, colour identification, and controlled release of active components. The technique is widely used to enhance the oral bioavailability, dispersibility, solubility, and stability of bioactive compounds (Gómez-Estaca et al., 2015; Klojdová et al., 2023; Li et al., 2015). Various coating materials, including lipids as well as natural and synthetic polymers, are employed to tailor delivery systems for different bioactives (Anirudhan and Binusreejayan, 2016; Rezagholizade-shirvan et al., 2024; Shishir et al., 2018). Micro- and nano-scale systems represent advanced formulation strategies involving the entrapment of active compounds within protective matrices or carriers, typically ranging from 1 to 1,000 μm and 1–1,000 nm, respectively. Micro-scale systems are particularly effective for protecting active ingredients and enabling controlled release during storage and application. In contrast, nano-scale carriers offer advantages such as increased surface area, enhanced cellular uptake, targeted delivery, and improved interaction with biological systems. These properties make nano-carriers especially promising for enhancing the efficacy of poorly soluble or unstable compounds, including plant-derived bioactive molecules and pesticides.

With latest clinical research it was examined that nanoencapsulation and microencapsulation enhancing the pharmacokinetic and pharmacodynamic performance of plant derived bioactive compounds, such as curcumin, quercetin, resveratrol, epigallocatechin gallate (EGCG), apigenin, and berberine (Ma et al., 2024). With different nanocarrier studies, essential characteristics of cancer, neurodegenerative, cardiovascular, metabolic, and inflammatory disorders have been improved in vitro as well as in vivo models (Kumar et al., 2025). Furthermore, prolonged circulation time and reduction of systemic toxicity is also achieved using novel strategy. In terms of clinical translation, nanoformulations are in progressive stage due to limitation on human trail system. Since, phytochemical nanoformulations such as Doxil, Abraxane, and Onivyde has improved therapeutic outcomes but regulatory bodies have not yet approved any of the plant derived phytochemical nanoformulations for commercial purpose (Chen et al., 2025).

The novelty of this review article is found in its comprehensive and application-focused view on phytochemical encapsulation techniques. In contrast to traditional reviews that treat phytochemicals and encapsulation methods independently, this paper links recent micro- and nanoencapsulation strategies with their direct effects on improving the biological activities, stability, and therapeutic effectiveness of bioactive compounds derived from plants. The article also highlights new nano-enabled methods such as electrospinning and advanced carrier based on polymers and lipids, which represent recent advances in the field of phytochemical delivery research. Furthermore, the review integrates applications across food, pharmaceuticals, and biomedicine, offering a multidisciplinary perspective on encapsulated phytochemicals instead of confining the discussion to one specific area. This comprehensive yet mechanistically linked approach enhances the article’s relevance for researchers engaged in nanotechnology, biotechnology, functional foods, and drug delivery systems. In previous articles, nanoencapsulation technologies or phytochemical delivery systems discussed independently. However, in present review both microencapsulation and nanoencapsulation approaches have been explained in a unique manner. Different classes of plant-derived bioactive compounds and their efficiency with both the approach have been presented in a simple way (Elkalla et al., 2023; Latif and Nawaz, 2026). Moreover, it emphasizes the interaction between encapsulation plan, phytochemical class, biological activity improvement, industrial applicability, and translational challenges. It also highlighted the latest advancement in nanotechnology such as electrospinning, nanostructured lipid carriers, stimuli-responsive systems, and regulatory considerations.

2 Genus contributing phytochemicals

Plants have always been beneficial to a healthy lifestyle since they not only provide food and bioactive compounds that may be used in medicine to improve human health, but they also make their surroundings healthier. Historically, plants and plant-based foods were primarily used for nourishment; subsequently, their therapeutic capabilities, to cure ailments, were discovered. According to Vinatoru, 2001, plants such as coriander and castor were documented in Egyptian papyruses and utilised in a variety of ways including Medicine, cosmetics, and preservatives. Among plant-derived bioactive compounds, terpenoids, phenolic acids, and alkaloids represent three major and pharmacologically significant classes.

For instance, quercetin, rutin, and kaempferol have been isolated from alcoholic extracts of Rauwolfia serpentine (Gupta and Gupta, 2015). It has been observed that R. serpentina contains about 147 plant-derived compounds, including 122 alkaloids, seven iridoid glucosides, six phenols, four anhydronium bases and four phytosterols, three glycosides, and one fatty acid. A comprehensive phytochemical review by researchers identified around 145 indole alkaloids in Rauwolfia species. Overall, the phytochemical profile of Rauwolfia includes alkaloids, iridoids, flavonoids, terpenes, sterols, sugars, and fatty acids (Oluwole et al., 2022). Similarly, other plants contribute diverse range of phytochemicals such as indoles, isothiocyanates, and sulforaphane from plants like broccoli; allylic sulphides from onions and garlic; and isoflavonoids from soybeans. Barley also contains trace levels of a wide variety of phytochemicals, including alkyl resorcinols, phenolic acids, sterols, tocols, and folate. The variation in phytochemical composition among different plant genera significantly influences the biological activity of their bioactive components.

There are different plant genera which are contributing a huge population of phytochemicals with significant biological and therapeutic activities. These phytochemicals are further categorized on the basis of their structure and function such as alkaloids, flavonoids, phenolic acids, terpenoids, tannins, and glycosides (Wani et al., 2023). Each bioactive compound has a specific dose in different genera and species due to their genetic, environmental and physiological changes (Latif and Nawaz, 2026). There are certain genera enriched in essential phytochemicals that would be demanding for pharmaceutical, nutraceutical and food industries. Each genus has unique biosynthetic pathways that determine the concentration, type and structural diversity of secondary metabolites produced. For example, genera rich in alkaloids, such as Rauwolfia, often exhibit pronounced pharmacological activities, including antihypertensive and neuroactive effects, due to the presence of indole alkaloids. In contrast, genera abundant in phenolic compounds and flavonoids, such as those found in fruits and vegetables, are typically associated with strong antioxidant, anti-inflammatory, and anticancer properties. Similarly, glucosinolate-rich genera like Brassica produce isothiocyanates, which are known for their chemoprotective and antimicrobial activities.

3 Aim for bioactive compound encapsulation

The endeavor of creating novel treatments for human disorders is highly challenging and complex. Researchers have provided a comprehensive analysis of various tools and methods used in cell-based systems, including natural approaches (e.g., bacteriophages and viruses) and artificial strategies (such as whole-cell entrapment in microgels, liquid cores, and multi-compartmentalized systems) (Figure 3). In this approach, living cells are confined within selectively permeable polymeric materials (such as membranes or beads), allowing controlled exchange of nutrients and metabolites while protecting them from host immune responses. This strategy has significant therapeutic potential for treating a range of human diseases, including applications in immunomodulation and cell-based therapies, where shielding cells from immune recognition helps prevent adverse defensive reactions by the host. In case of bioactive chemicals, there are some serious limitations, but natural bioactive substances encapsulated on various nano- or micro platforms have the capacity to overcome them. This includes things like enhancing their pharmacokinetics, which controls things like absorption and overall bioavailability, as well as their physicochemical aspects, such as solubility and stability.

Encapsulation of bioactive substances has a number of advantages, which can be described as follows.

3.1 Enhanced stability

The majority of plant bioactive chemicals are sensitive to heat, light and pH changes, resulting in a unpleasant flavour/colour (Prakash et al., 2018; Rezaei et al., 2019; Soukoulis and Bohn, 2018). For instance, because of their potential therapeutic properties bioactive compounds like Anthocyanins are increasingly being consumed as natural phytochemicals and/or efficient foods (de Almeida Paula et al., 2018; Rashwan et al., 2023) However, Anthocyanins are exposed to a variety of extreme conditions during product development, such as heat sterilization, blending, and high-pressure mixing, among others, which can damage the Anthocyanins, resulting in the formation of less dynamic by-products via rapid oxidation or reduction reactions (Aditya et al., 2017; Mueller et al., 2018). One of the better choices for improving Anthocyanins stability is to encapsulate them in micro- or nano-carriers. To stop these factors from breaking down bioactive molecules in vitro or in vivo, they can be encapsulated (Ijod et al., 2024).

3.2 Improved biological activities

Bioactive molecules are chemically unstable and prone to oxidative degradation, despite their various health benefits. Pure bioactive compounds are being utilized in food and medicinal formulations but are similarly limited due to rapid release, small solubility, and low bioavailability. Phytochemical encapsulation protects them from challenging environmental conditions, improves their physicochemical functions, and boosts their health-promoting and disease-fighting properties (Klojdová et al., 2023).

3.3 Enhanced therapeutic activities

The field of research known as “nanotechnology” focuses on the study of the synthesis, characterization, and utilization of nanomaterials and functional systems of nanoparticles with sizes ranging 1 and 100 nm (Greish et al., 2018). In addition to their small size, these materials are of interest these days because of their unique physicochemical features at these dimensions, which allow a more scalable interaction with cells and biomolecules. The use of nanotechnology in medicine, or nanomedicine, has sped up the development of new, more effective diagnostics and therapies, especially for complicated illnesses like Parkinson’s, diabetes, and cancer (Gmeiner and Ghosh, 2014; Nikalje, 2015). One of the most exciting developments in biomedical research is the usage of nanoparticles as carriers for gene-therapy because of their simple and straightforward manufacturing, ability to be functionalized with various moieties, minimal immunogenicity, and low toxicity (Chauhan et al., 2026; Muhammad et al., 2020). The most popular nanoparticles along with their origin is shown in the figure (Figure 4).

After encapsulating the material into numerous systems including solid lipid nanoparticles (SLN), liposomes and micelles results in an improved bioavailability of weakly absorbable bioactive compounds like polyphenols have been reported (Puligundla et al., 2017). Approaches like nanostructured lipid carriers (NLCs), nanoemulsions, nanosuspensions, nanoliposomes, biopolymer nanoparticles NPs or micelles made of polysaccharides and/or proteins have been established (Jafari, 2017).

3.4 Improved physicochemical properties

By delivering bioactive chemicals in spherical, uniform-size, and free-flowing powders, micro- or nanoencapsulation can improve general physicochemical qualities like shape and wettability while also facilitating overall processing during their manufacture (Bertoni et al., 2019; Dima et al., 2016) The likelihood of variance in the quality of the last products is reduced as a result of this improvement in powder flow characteristics (Guajardo-Flores et al., 2015). Due to the bioactive compound’s dispersion in the amorphous form inside the matrix, the rate of dissolution of weakly aqueous-soluble bioactive compounds like naringin and quercetin was documented to be boosted by 20–55 percent (Pai et al., 2015) and 100 times, respectively. A brief idea about various encapsulation techniques used for the bioactive compound to attain desired traits is discussed in Table 1.

TABLE 1. Plant based bioactive compounds commonly encapsulated using nanoencapsulation (A) and microencapsulation (B) Strategies.

3.5 Safety and toxicity of encapsulation

Although research on nanomaterials is in limelight due to its vast advantages towards improvement in stability, bioavailability, and targeted delivery of bioactive compounds. On the other hand, safety concerns about it are remain significant. It was reported that nanotoxicity is influenced by various factors like particle size, shape, surface charge, composition, and dosage that can disturb cellular and biological responses (Assidqi et al., 2025). Moreover, during observation, nanoparticles may show unique patterns that make eligible to them to access the biological barriers and deposit in different tissues and organs such as liver, spleen, kidneys, lungs, and brain (Yakubu et al., 2024). This may lead to oxidative stress, organ inflammation, cellular damage, or other stochastic effects in prolonged accumulated situation. Furthermore, it is a major challenge in front of monitoring and semi-approval bodies to establish a standard guideline for the characterization, functioning, safety assessment, and approval of nanomaterial-based products due to their complex physicochemical properties (Ali et al., 2023; Ghosh and Kumar, 2024). It can also raise a major question on environmental sustainability, as the approved nanomaterials at the time of production, use, or dispose out may affect ecosystems security, beneficial soil microorganisms, aquatic organisms, and food web. However, an empirically approved regulatory guidelines with environment risk evaluation and assessments should be mandatory for the safe use of nanomaterials for mankind purposes.

4 Nanotechnology-based encapsulation strategies for novel bioactive compounds

4.1 Micro and nano-emulsions

Oil-in-water (O/W) or water-in-oil (W/O) nano-emulsions are colloidal, thermodynamically unstable dispersions that are stabilized by an interfacial layer of surfactant molecules and occasionally co-surfactant molecules (Gupta et al., 2016; Solans et al., 2016). According to reports, microemulsions are thermodynamically stable colloidal dispersion. A large number of lipophilic compounds can be delivered by these nanosystems, which is advantageous while also shielding the bioactive from enzymatic, hydrolytic, or oxidative destruction (Rai et al., 2018). Increasing the bioavailability of bioactive drugs is the primary motivation for employing drug delivery methods based on nanoemulsions or microemulsions (Shukla et al., 2018). Techniques, divided into two main groups, which can be used to incorporate this: both high- and low-energy techniques. The NEs were produced in solvent-free environments using a basic low-energy technique either with or without heating, and when protected from light during storage at room temperature, they remained stable (Oliveira et al., 2017b; 2017a; 2016). To turn the discrete, incompatible components of nanoemulsions into a dispersion, some external energy must be added. High-energy techniques use strong forces to mix and disrupt the water and oil phases, creating small droplets with high kinetic energy. For the preparation of nanoemulsions, mechanical tools like high-pressure homogenizers or ultrasonication are typically used (Gupta et al., 2016). As a result, high-energy methods can create very stable nanoemulsions with tiny particle sizes. Conversely, low-energy techniques make use of the inherent physicochemical features of formulation ingredients, which only need a small amount of additional external energy to produce droplets. Self-emulsification and phase inversion emulsification are two examples of low-energy techniques for creating micro- and nanoemulsions. When they are considered energetically efficient, the current focus is on creating nano- or microemulsions utilizing low-energy techniques. Additionally, it is easy to use and does not call for expensive or specialized equipment (Kumar et al., 2019). Another choice for delivering hydrophobic chemicals is nanoemulsion Numerous nanoemulsions (NE) have been created to improve the pharmacological effect of oily extracts from the genus Pterodon. In this contextual, a study recommended producing NE (O/W) using the essential oils of Pterodon emarginatus. The most effective NE was created by combining polysorbate 80 (1:1) and essential oils at amounts of 0.25 percent (w/w), utilizing a straightforward organic solvent-free low-energy procedure. The main components of the extensively studied amber-colored oleoresin from P. emarginatus are the volatile essential oils, which are composed of a mixture of terpenoids, including the diterpenes with vouacapan skeleton (Oliveira et al., 2017a). Studies conducted recently have concentrated on the creation of NE for the transportation of this oleoresin (NE P. emarginatus oleoresin) for larvicidal treatments against the primary vectors of dengue and lymphatic filariasis, Aedes aegypti and Culex quinquefasciatus, respectively (Oliveira et al., 2017b; 2016).

NEs have recently proven to be effective at protecting human keratinocytes from ultraviolet (UV) radiation at 10 μg/mL. P. emarginatus fruit oleoresin was used to create NE. These processes were influenced by phenolic and terpene chemicals found in P. emarginatus extracts. In addition to its anti-oxidant qualities, the NE could alter the epithelial cells’ inflammatory profile. Keratinocytes after UV exposure displayed lower levels of IL-6 and IL-8, two pro-inflammatory cytokines (Pacheco et al., 2019). The oil activity was maintained even after heating the nanoformulation to 65 C and using a high energy emulsification technique.

Restricted cellular permeability and low water solubility are a substantial hurdle in the development of medicinal drugs. Nanosystems and micro mobilization can help to overcome this constraint. However, due to their weak water solubility, which causes low bioavailability and hinders practical application, their therapeutic utility is still constrained. To fix this problem Particulate nanocarriers can be utilized to distribute hydrophobic and/or lipophilic compounds in water, prevent degradation of the encapsulated chemical, alter the pharmacokinetics of the medicine, and increase therapeutic efficacy (Yetisgin et al., 2020).

While the essential oils are composed of volatile lipophilic compounds with antispasmodic and anti-inflammatory properties, the oleoresins extracted from the fruit are a blend of lipophilic molecules, including the volatile and non-volatile components (Oliveira et al., 2016). Their therapeutic value is still limited, nevertheless, due to their weak water solubility, which results in low bioavailability and prohibits practical usage. To fix this problem Particulate nanocarriers can be utilized to encapsulate hydrophobic and/or lipophilic compounds in water, prevent degradation of the encapsulated chemical, alter the pharmacokinetics of the medicine, and increase therapeutic efficacy (Yetisgin et al., 2020). Fruit, seed oils and extracts from the Pterodon genus are widely known for their medicinal properties and provide a broad spectrum of active compounds, they are frequently utilized in conventional medicine (Hoscheid and Cardoso, 2015). Metal, lipid, and polymeric nanostructured systems can all be grouped together (Ding et al., 2020). Alkali and noble metals make up the core of metallic nanoparticles (Shahalaei et al., 2024; Yetisgin et al., 2020).

These fall into the category of hard nanoparticles with a rigid core, that may have a limited capacity for drug loading or attaching to the surface. Materials having a flexible central core known as “soft nanoparticles” are useful for loading drugs (Sangtani et al., 2017). The flexible cores of the polymeric and lipidic nanoparticles can momentarily deform due to tension or contact with surfaces. Colloidal particles with a polymer foundation, including nanospheres and nanocapsules, allow the medicine to be absorbed or encapsulated in the polymer. According to characteristics including temperature, pH, size, charge and drug-loaded nanocarriers, they circulate long enough to accumulate in target tissue in passive targeting (Cardoso et al., 2018; Cavalcante et al., 2021). Active targeting, in contrast, attaches a biological marker to nanocarrier exterior layer that will be recognised by receptors expressed on the target cell surfaces (also known as ligand-based targeting) (e Silva et al., 2018; Linderman et al., 2025).

4.2 Polymeric nano-particles

To greatly improve delivery, therapeutic bioactive substances can be covalently bound, encapsulated, or adsorb to the unique surface chemistry of polymeric nanoparticles. Due to their advantageous qualities, including as strong biocompatibility, simple design and preparation, structure changes, and intriguing biomimetic features, biodegradable polymeric nanoparticles are increasingly being used (Faridi Esfanjani and Jafari, 2016). To assess the metabolism and long-term safety of polymeric nanoparticles for the treatment of chronic illnesses, more research is necessary. The sole difference between nanocapsules and microcapsules is their size, yet reducing the size of the particles to the nanometer range significantly improves their physicochemical characteristics improved drug dissolution, stabilization of labile drug membrane permeability, and controlled drug release are all benefits of nanoencapsulation. Polymeric nanocapsules enable the parenteral and oral administration of bioactive chemicals as a result. It has been demonstrated that the form and quantity of wall makers in nanocapsules affect the encapsulated compounds’ size, surface characteristics, stability, ability to load drugs, water solubility, and release profile (dos Santos et al., 2016). To give the nanocapsules the needed functionality, it is essential to choose the right wall-forming substance. By carefully assembling two separate biopolymers, like protein and polysaccharide molecules, these natural biopolymers are created. Another innovative and promising method that increases the stability of NPs is the protection of bioactive component production via electrostatic interactions between positively charged proteins and negatively charged polysaccharides.

So, rather than pure single biopolymer NPs, polysaccharide–protein nanostructures are more fascinating. Biopolymers that have undergone substantial research for food encapsulation include zein, chitosan, gelatin, sodium alginate, gluten, maltodextrins, cellulose, albumin and whey protein (Bhaskar et al., 2023; Khoshakhlagh et al., 2017; Murthy et al., 2018). In particular, milk proteins, primarily those from whey, have received a lot of attention in research on polysaccharide–protein complex systems (Ghasemi et al., 2017). In a recent study, D-limonene was nanoencapsulated at different pH levels using pectin and whey proteins. Pectin was used at 0.5%, 0.75% and 1% w/w (3, 6 and 9) (Ghasemi et al., 2018). The results showed that these wall materials could nanoencapsulate significant volume of D-limonene with high stability (EE of 83.0%–98.5%). Polymers are used to create polymeric nanoparticles. Biodegradable polymers are frequently made of synthetic poly (-caprolactone) (PCL), (poly (lactide) (PLA), poly (lactidecoglycolide) (PLGA) and poly (ethylene glycol) (PEG) as well as natural polymers (alginate and chitosan). To improve the bioavailability, controlled release, and extended release of polymeric nanoparticles, bioactive substances can be conjugated to polymers or added to them. Nanoprecipitation, Emulsification–diffusion and solvent evaporation techniques are frequently used to create polymeric nanoparticles. To enhance the properties and bioactivities of trans-Resveratrol, EGCG, and curcumin, these compounds have been encapsulated within PLGA nanoparticles. PEG, which is extremely hydrophilic and little immunogenic, is another often utilized biocompatible polymer. PEG is frequently utilized as the hydrophilic shell of nanoparticles to increase stability and extend circulation time. Among the most popular polymers for nanoencapsulation are poly (lactic acid), poly (glycolic acid) and their copolymer poly (lactide coglycolide), all of which are biocompatible and biodegradable (Liu and Feng, 2015). Additionally, the general therapeutic effectiveness of PLGA-based silymarin nanocapsule was also demonstrated to be improved by sustained release, increased bioavailability, and selective toxicity against prostate cancer cells. In an animal model, the formation of diabetic cataracts was likewise stopped by curcumin nanoencapsulation with PLGA.

Nanoencapsulation has been used to enhance paclitaxel, an anticancer phytochemical obtained from Taxus brevifolia that is weakly soluble in aqueous solution and is also metabolized by cytochrome P450 metabolic enzymes and P-glycoprotein-mediated efflux. Mucoadhesive polymers can be used to coat bioactive substances to boost their oral bioavailability, which can make sustained, close contact with the surfaces of the GI tract and promote absorption. Because chitosan adheres to the negatively charged mucosal surface, it is often utilised to coat polymeric nanocapsules, enhancing absorption and consequently the therapeutic impact (Chuah et al., 2014). Capsaicin, a naturally occurring bioactive molecule extracted from peppers, was nanoencapsulated with some natural coating materials like acacia and gelatin, the odour and rapid breakdown of the chemical were concealed. The pH-dependent release and heat stabilisation of bioactive compounds have been achieved with natural resource-based encapsulating materials (Akbari and Wu, 2016; Kamble et al., 2025; Pinheiro et al., 2015).

5 Magnetic and metallic nanoparticles

Creation of effective delivery methods plant extracts or bioactive compounds have been effectively used to create metal nanoparticles with improved antibacterial properties (Griffin et al., 2017; Jain and Mehata, 2017) In a previous study, aqueous extracts of P. emarginatus were recently used to create silver nanoparticles in this context (AgNPs-PE) (Oliveira et al., 2019). Similar to this, Toledo et al., 2020 showed AgNPs-PE had bactericidal and fungal activity when combined with hyaluronic acid and 1% gentamicin sulphate (AgNPs-PEG) (AgNPs-PEG-AH2) (Toledo et al., 2020). Magnetic iron oxide nanoparticles stand out among the different nanosystems due to their large surface area and unique magnetism-related characteristics (Cardoso et al., 2018). Manufacture of iron oxide magnetite (Fe₃O₄) or maghemite (Fe₂O₃) nanoparticles, several methods have been reported. The most prevalent ones include hydrothermal synthesis, micro-emulsion, co-precipitation, and sol-gel synthesis. Co-precipitation, however, has the benefits of low cost, excellent product purity, and environments free of organic solvents, offering tremendous promise for applications in a number of technological fields (Nazari et al., 2014).

6 Lipids nanoparticles

Lipid nanoparticles can be classified into two types: solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). Their fundamental structural differences produce distinct loading capacities. Lipid nanoparticles are useful for encasing hydrophobic compounds because they have a lipid core.

6.1 Nanostructured lipid carriers (NLCs)

NLCs were created to address the low-loading issue. Their hydrophobic cores are made up of solid and liquid lipids mixture, which results into less organized crystalline structure and a high loading capacity for hydrophobic bioactive compounds (Beloqui et al., 2016). Phase inversion, ultrasonication, solvent evaporation/emulsification, hot/cold/high-pressure homogenization, and others are popular preparation techniques. Additionally, there are two fundamental categories into which nanostructures can be divided: single-core and multicore. Jafari has specifically characterized binary mechanisms of the nanocapsule and nanosphere in the context of nanocarriers (Jafari, 2017). In order to account for the primary method or component used to create the nanocapsules, author divided nanoencapsulation methods into five classes.

• Natural nanocarriers, such as amylose nanostructures, cyclodextrins, caseins, and nanocrystals
• Liposomes, nanoemulsions, and nanostructured lipid carriers are examples of lipid formulations
• Unique tools (electrospun nanofibers, nanosprayed dry particles, and electrosprayed nanoparticles)
• Contrasting methods (carbohydrate nanogels and protein nanotubes)
• Functional biopolymeric NPs.

These NLC showed additional advantageous traits over those other NPs, for instance higher loading volume and extended physicochemical stability, because their matrix is a blend of solid and liquid lipids (Domínguez et al., 2021). Although NLCs have certain problems with aggregation, sedimentation, and thermodynamic instability (McClements, 2020), their higher loading capacity, drug stability and decreased drug ejection have sparked a lot of attention in creating NLC transport systems for different ways of administration.

In the near future, it is anticipated that the therapeutic use of NLCs in treating chronic ailments, such as obesity and its associated conditions, would nurture as a consequence of an increase in the quantity of NLC products that are patented and new knowledge about the transport, biodistribution, and functional processes of NLCs (Nayak et al., 2025).

6.2 Solid lipids nanoparticles (SLN)

Lipid-based nanocarriers, such as SLNs, have shown promise in replacing traditional colloidal carriers such polymeric micelles, liposomes, and emulsions (Lin et al., 2017). SLNs developed an effective tool even applied to treat cancer (Akanda et al., 2023). The hydrophobic lipid core of SLNs, which are the first generation of lipid nanoparticles, is solid at body temperature and is surrounded by a monolayer of phospholipids. Currently, other phenolic compound delivery techniques are also being explored. SLNs can delay the release of the encapsulated chemicals, are biocompatible, very stable, and have good encapsulation efficiency (Kumar and Kumar, 2014). Lipid nanoparticles NPs have been employed in the food industry in this regard, including nanoliposomes, nanoemulsions, SLN and NLC (Pateiro et al., 2021). Chemicals can also be added to the surface of SLN to functionalize it and aid in medication absorption and delivery to the targeted location of action (Liu and Feng, 2015). The bioactive substances in SLNs are a component of the matrix’s solid lipid core (Figure 5), stabilized by a surfactant or a blend of them. A liquid nanoemulsion is a dispersion that consists of an oil phase, a water phase, and a surfactant that is stable either thermodynamically or kinetically (LNE). The dispersion phase, which likewise has a very low oil/water interfacial tension, frequently contains small particles or droplets with sizes ranging from 5 nm to 200 nm.

6.3 Liposome mediated encapsulation

The lipid-based particles known as liposomes consist of one or more phospholipid bilayer membranes that surround an aqueous core (Akbarzadeh et al., 2013). A spherical vesicle made up of one or more lipid bilayers is known as a liposome. Most frequently, phospholipids like phosphatidylcholine make up liposomes. In an aqueous solution, phospholipids with two hydrophobic fatty acid tails and a hydrophilic head self-organize into the recognizable lipid bilayer structure. Liposomes can contain a wide range of hydrophilic and/or hydrophobic substances (Shishir et al., 2020). The physicochemical qualities of bioactive compounds, such as stability and solubility, are also improved by liposomal formation. When combined with 3-oxo-C12- homoserine lactone, liposomes improved the chemical stability of resveratrol and were found to decrease tumour development in murine tumour models by approximately 70%. As anthocyanins are soluble in water, they can be incorporated into the internal aqueous phase of liposomes (Lee and Na, 2020). anthocyanins can be protected against environmental deterioration caused by light, pH, enzymes, and other factors by being encapsulated in liposomes. Because of their biodegradability, targeting, biocompatibility and controlled release qualities, liposomes are a better delivery mechanism (Zarrabi et al., 2020). Encapsulation in liposomes can limit the number of anthocyanins that are degraded by ascorbic acid. A prospective cosmeceutical treatment for disorders of skin pigmentation, the nanoliposome-encapsulated enriched-phenolic fraction of Pistacia vera L extract exhibits a range of bioactivities, including anti-inflammatory, antioxidant and anti-melanogenic properties (Oskoueian et al., 2020). Momordica charantia and quercetin both demonstrated improved bioactivity and stability with their respective nanoliposomal formulations (Gayathry and John, 2022; Rezaei Erami et al., 2019) For food bioactive compound or nutraceuticals, various nanoencapsulation techniques have been used recently. For instance, techniques like biopolymer nanoparticles NPs and micelles consisting of polysaccharides or proteins, nanoemulsions, nanosuspensions, nanoliposomes, and nanostructured lipid carriers (NLCs) have been developed (Jafari, 2017). When it comes to clinical translation, liposomes and polymer-based nanoparticles are the most advanced, with cancer therapy being the main use.

7 Niosomes

One of the best encapsulating techniques for delivering bioactive chemicals is the niosome, which is mostly composed of nonionic surfactant vesicles. They are created using self-assembly technique in certain aqueous solutions containing nonionic amphiphiles. Niosomes are mostly utilised in the cosmetics industry. Niosomes are now used to encapsulate bioactive substances. Niosomes have many advantages, such as their high biocompatibility, minimal toxicity, capacity to stimulate the immune system, and suitability as components of targeted drug administration (Ge et al., 2019). Niosomes are typically prepared using nonionic surfactants like Brij, Spans, Tweens, polyglycerol alkyl ethers, polyoxyethylene alkyl ethers, glucosyl dialkyl ethers, ester-linked surfactants, crown ethers, and many more. Additionally, niosomes can be stabilised by adding a proper amount of cholesterol. This is because it's possible that the bilayer membrane will become more flexible as a result of the interaction between cholesterol and a nonionic surfactant in the niosome structure. The typical encapsulation effectiveness of niosomes is between 10% and 40%, however other studies claim that it can reach up to 75%–90% (Ge et al., 2019; MohdMaidin et al., 2019). Both hydrophobic and hydrophilic substances can be contained by niosomes. Hydrophilic chemicals are contained in the inner aqueous portion of the bilayer, while hydrophobic portion of the bilayer traps hydrophobic substances. Anthocyanins are hydrophilic molecules; they have been confined in the innermost aqueous phase of niosomes (Fidan-Yardimci et al., 2019). Niosomes are more stable because of their nonionic surfactants, which have higher physical and chemical stability than lipids. The anti-inflammatory efficacy was greatly sustained by niosomal encapsulation of anthocyanins from purple corns of Zea mays and blue petals of Clitoria ternatea, especially at 8 h after topical administration (Priprem et al., 2015). Additionally, niosomes are a superior substitute for encapsulating and protecting bioactive molecules from the gastrointestinal system’s acidic and enzymatic degradation as well as from acidic food products, such as beverages. According to a study, niosomes are more resistant to certain acidic and enzymatic breakdown conditions (Aditya et al., 2017). Niosomes may experience problems with encapsulated bioactive substances that aggregate, fuse, and leak. Proniosomes have been created to address this issue. These are dry, free-flowing kinds that, upon modest agitation with hot water, spontaneously create niosomes. Additionally, niosomes shielded the extract from direct contact with several environments (reducing agent, weak base/acid salt), which enhanced the stability (Manosroi et al., 2020; Mawazi et al., 2025).

8 Hydrogels

The term “hydrogel” refers to a cross-linked network of hydrophilic polymers with a three-dimensional shape (Fu et al., 2021; Thakur et al., 2018). Hydrogels can be produced using a water-soluble polymer with a variety of chemical constituents and bulk physical properties. Hydrogels can hold a lot more water than biopolymer particles because they have a large inner structure that includes a biopolymer gel network (Wei et al., 2019). Alginate nanohydrogels, lactoferrin and starch nanoparticles, lactalbumin nanotubes are examples of single-particle biopolymer systems. Other single-particle biopolymer systems include polysaccharide-protein nanocomplexes (e.g., pectin-whey protein nanocarriers) (Sosnik and Menaker Raskin, 2015; Wei et al., 2020) When polymers have hydrophilic groups like azanide (NH₂), hydroxyl (OH), carboxyl (COOH), amides (CONH₂ or CONH), and sulfonic acid, they acquire the hydrophilic qualities of hydrogels (SO₃H). Hydrogels are therefore used in many different applications, including tissue engineering, diagnostics, regenerative medicine and cellular immobilization. Increased β-carotene stability and bioavailability in vitro in filled hydrogel made from starch blends with varying granule sizes (Kim et al., 2023). Large amounts of water can be absorbed by hydrogels, and even after swelling, they can keep their original shape without dissolving. Thus, the release of diverse therapeutic agents such as small molecules and macromolecules employing different hydrogel systems, such as DNA-hydrogels, supramolecular hydrogel, bio-inspired hydrogels, and multifunctional as well as stimuli-responsive hydrogels, can give spatial and temporal control (Narayanaswamy and Torchilin, 2019; Thakur et al., 2018). A unique system is created by the hydrogels’ matrix, which contains a significant amount of water.

9 Electrodynamic processes

As an alternative to more known and widely used methods like microencapsulation, electrodynamic encapsulation technologies like electrospraying and electrospinning have gained more attention recently (Alehosseini et al., 2018; Jacobsen et al., 2018). The high voltage electrostatic force during electrospraying causes the drug-loaded liquid solutions to condense into tiny droplets. As droplets move towards the ground electrode, they begin to evaporate (Alehosseini et al., 2018). While electrosprayed particles are created by a low level of molecular interaction, electrospun threads are created by a high level of molecular contact with the liquid. In the traditional spray-drying procedure, materials are dried and encapsulated at high temperatures between 170 °C and 220 °C, which has the potential to destroy thermolabile medicinal molecules (Jacobsen et al., 2018). The following benefits are also provided by electrodynamic encapsulation of bioactive substances (Drosou et al., 2017; Ghorani and Tucker, 2015; Wen et al., 2017a; 2017b).

• It is a somewhat easy, affordable, and adaptable way to make nanomaterials.
• Better bioavailability is achieved by nanoscale materials with a high surface to volume ratio.
• The technique can be applied to a variety of encapsulating materials.
• Improved bioactive compound stability.
• It has the potential to increase large-scale manufacturing.

Bioactive substances that are hydrophilic or hydrophobic can both be encapsulated.

In order to improve beta-carotene’s stability and bioavailability in its solubilized form, electrospraying was successfully used (Basar et al., 2020). Free beta-carotene destroys in 180 min when exposed to UV radiation, however encapsulated beta-carotene only decreases by 20%. Numerous polymers, such as polysaccharides including cellulose and its derivatives, starch, guar gum, chitosan, pectin and alginate, are amenable to electrodynamic processing (Wen et al., 2017b). The morphology of the electrospray fibers or capsules was discovered to be influenced by the polymeric solution’s surface tension, viscosity and electrical conductivity (Gómez-Mascaraque et al., 2016). Nanoencapsulation is a technique used to immobilize active biological molecules within nanoscale carriers starting from 1 to 1,000 nm to improve stability, solubility, bioavailability, and -controlled dosage release. Different nanoencapsulation technologies have distinct advantages and limitations.

Table 2 presents a comparative study of microencapsulation and nanoencapsulation systems employed for phytochemicals delivery.

TABLE 2. Comparative analysis of different technical systems for phytochemicals compound delivery.

10 Solid dispersion and micelle

Numerous hydrophobic bioactive compounds can be incorporated into micelles, which have a hydrophobic core. The micelle surface can be grafted with particular targeting ligands to produce “targeted micelles” for diseased tissues and cells. Micelles are simple to make and have extended circulation times, high levels of stability, and improved cellular absorption, but they have a high surfactant content, poor encapsulation effectiveness, and limited loading capacities (McClements, 2020). A class of amphiphilic colloids known as micelles are composed of amphiphilic monomers. A few well studied methods for producing micelles are filtration, solid dispersion, oil-in-water emulsion, solvent evaporation, and dialysis (Fritz et al., 2018). Some amphiphilic polymers can also form micelles, which are referred to as polymeric micelles.

One of the most popular techniques for increasing the solubility and bioavailability of medicines that are only sporadically soluble in water is the solid dispersion technique. As their dissolution requires overcoming the lattice energy, crystalline medicines frequently have low solubility in aqueous-based solvents (Li et al., 2013). Such crystalline pharmaceuticals are more easily soluble when they are formulated into amorphous solid dispersions because the solid dispersions encapsulating polymers confine the medications in an amorphous state, facilitating their dissolution in aqueous solvents. It has been demonstrated that a variety of cellulose derivatives considerably improve curcumin solubility, protect it from chemical deterioration, and trigger pH-dependent release (Li et al., 2013). Curcumin was prepared in a variety of formulations, including nanocrystal solid dispersions made with hydroxypropyl cellulose and amorphous solid dispersions made with hydroxypropyl methylcellulose acetate succinate, and nanoemulsions. It has already been proven that polymeric micelles improve the bioactivity and solubility of bioactive substances. Naringenin was loaded into polymeric micelles made of pluronic P123 and solution HS15, which resulted in a protracted release of the drug and a significant rise in its cytotoxicity against cancer cell lines. Paclitaxel’s oral bioavailability in glycyrrhizic acid micelles was also exposed to be six times greater than that of Taxol (Yang et al., 2015). The hydrophobic core has been created using solid lipids made of triglycerides, fatty acids, waxes, or combinations of aforementioned lipids. The SLN structure is often stabilized with one or more surfactants. According to a previous study, SLNs provide a number of benefits, including the increase of the solubility, stability, bioavailability, and bioactivity of the encapsulated phytochemicals as well as their protection from enzymatic degradation and metabolism. They offer a safe method for delivering bioactive phytochemicals that are poorly soluble in water, improving their stability as well as boosting their bioavailability and permeability (Mehnert and Mäder, 2012).

11 Conclusion and future insights

The future development of nanoencapsulation and microencapsulation technologies for plant-derived bioactive compounds is anticipated to focus on the design of personalized delivery systems tailored to individual physiological conditions, disease states, genetic profiles, and nutritional requirements. Nanoencapsulation has emerged as a promising approach for improving the stability, bioavailability, and functional efficiency of bioactive compounds. Techniques such as coacervation, emulsification, inclusion complexation, supercritical fluid technology, and nanoprecipitation solvent evaporation have showed effective in protecting phytochemicals from environmental degradation and enhancing their biological activities. In particular, nanoprecipitation and solvent evaporation methods are well suited for lipophilic compounds. Drying techniques, including spray drying and freeze drying, further influence the physicochemical properties and storage stability of nano encapsules.

However, further research is required to optimize processing parameters across different encapsulation techniques to achieve uniform particle size, enhanced stability, and controlled release profiles. Comparative and standardized studies will be beneficial in identifying the most efficient and scalable methods. Future investigations should also focus on the development of advanced delivery systems, such as stimuli-responsive and targeted nanoencapsulation platforms, to improve site-specific delivery and therapeutic outcomes. In addition, while in vitro studies have shown encouraging results, more in vivo and clinical studies are essential to establish the safety, bioavailability, and long-term effects of nanoencapsulated bioactives.

Detailed toxicological assessments, including their interaction with biological systems and potential accumulation, are crucial. Emphasis should also be placed on developing cost-effective, scalable, and environmentally sustainable production techniques to facilitate industrial application. From an industrial perspective, nanoencapsulation holds significant potential in the food, pharmaceutical, and nutraceutical sectors by enabling the development of value-added products with enhanced shelf life, improved efficacy, and controlled delivery of active ingredients.

Finally, the establishment of clear regulatory guidelines and safety standards for nano-based food and pharmaceutical products remains a key priority. Future regulatory bodies should incorporate empirically evaluated and standardized protocols for characterization, toxicological evaluation, biodistribution research, and long-term environmental risk assessment of nano-enabled products. In addition, large-scale manufacturing remains a major bottleneck due to issues related to process reproducibility, formulation stability, production costs, and batch-to-batch consistency. Addressing these challenges through interdisciplinary research will be critical for translating nanoencapsulation technologies into safe, effective, and commercially viable solutions for improving human health.

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Footnotes

Edited by: Rahul Dilawari, University of Texas Medical Branch at Galveston, United States

Reviewed by: Teguh Wahyono, National Research and Innovation Agency (BRIN), Indonesia

Lamia Taouzinet, Centre de recherche en Technologies Agro-Alimentaires, Algeria