INTRODUCTION:

Essential oils (EOs) can be extracted from a wide range of plant materials, including seeds, flowers, leaves, roots, wood, twigs, bark, and buds. EOs are the secondary volatile metabolites of aromatic plants and have a potent antibacterial and therapeutic effect¹. which are comprised of volatile substances including terpenes, esters, amines, alcohols, ketones, phenolics, and amides². The primary component of essential oils is terpenes, which are made up of multiple isoprene units (C₅H₈). Sesquiterpenes (C₁₅H₂₄), monoterpenes (C₁₀H₁₆), and diterpenes are a few examples of the various types of terpenes that have been developed and typically constructed on the number of carbon atoms (C₂₀H₃₂)³.

The most prevalent forms of terpenes, monoterpenoids, and sesquiterpenoids are synthesized by enzymatically adding oxygen molecules and removing methyl groups from terpenes⁴. According to a literature review, Most EOs have a broad range of effects, such as antiparasitic, bactericidal, antiparasitic, virucidal, anticancer, analgesic, anti-inflammatory, and sedative properties⁵. To extend the shelf life and quality of the products, essential oils have drawn a lot of interest recently from industries such as medicine, agriculture, and the food sector⁶. However, the key characteristic limitations that prevent essential oils from being employed due to their high hydrophobicity, oxidation sensitivity, volatility, solubility and low stability, solubility, and undetermined mechanism of action⁷. As a result, a solid technique to get beyond the current drawback of products made with essential oils is to use appropriate coating materials as the carrier agents⁸. All scientific disciplines which deal with particles between 1 and 100 nm in size, often use nanotechnology. The practical application of phytochemicals is thus improved by the increased surface area of nanoscale particles⁹. The technique of encapsulating essential oils in nanoparticles is expanding quickly in the present day to enhance their bioactivity, stability, and targeted delivery along with the controlled release in the system. EOs are often coated with a range of materials, including cellulose, chitosan, starch, pectin, alginate, guar gum, carrageenan, dextran, cyclodextrins, and xanthan.

Essential oils' preservative and therapeutic characteristics:

The pharmacological effects of essential oils are extremely diverse and include antibacterial, anti-diabetic, anti-cancer, insecticidal, antioxidant, anti-inflammatory, anti-ulcerogenic, and anti-anxiety effects¹⁰. Essential oils can be employed as preferred substitutes to synthetic preservatives because they reflect their biological properties as fumigants and have little to no adverse effects on health¹¹. The US Food and Drug Administration continues to categorize the majority of EOs, including thyme, clove, nutmeg, oregano, basil, cinnamon, and mustard¹². A few more essential oils have been investigated by Aras et al. for their antifungal and antibacterial properties against bacterial and fungal species¹³. Essential oils also showed strong functional qualities such as antioxidant, acetylcholinesterase inhibition, antidiabetic, anti-inflammatory, cognitive impairment, anticancer activities, etc. According to Byrne and Russon the visual cortex level of many neurotransmitters, including acetylcholine, noradrenaline, and serotonin, which are involved in the inhibition of signal transmission, is known to decrease in people with Alzheimer's disease (also known as old age dementia)¹⁴. The key target site of action for drugs to treat Alzheimer's disease is the suppression of the acetylcholinesterase (AchE) enzyme activity. Consequently, plant substances with the potential to block acetylcholinesterase include galantamine and the alkaloids of the Amaryllidaceae group. These substances could be employed to treat Alzheimer's disease.

Nanotechnology: Technique to increase the bioavailability of EOs

Despite having high biological activity, Eos and their biologically active substances have limited industrial use due to their high volatility, intense aroma, photosensitivity, hydrophobicity low solubility, and stability¹⁵. To expand the range of applications for essential oil-based products at the industrial level, additional creative research is required in the area of unique, safe, and cost-effective delivery systems¹⁶. In this context, using nanoencapsulation technology has significant promise to increase the effectiveness of essential oils in the food system¹⁷. Nanoencapsulation offers several advantages, such as protecting essential oils from deterioration, improving solubility in the aqueous medium, muffling intense aromas, preventing negative interactions with food components through high bioavailability, controlled release, and limiting the optimal dose to accomplish preservative and functional effects¹⁸. The concentration of EOs in the food sector, which includes water-rich phases and significant fluid interfaces, can be increased through nanoencapsulation, which also increases the bioactivity, target specificity, and circulation time of the microorganisms¹⁹. According to Gundewadi et al. the two most prevalent food spoilage fungi, Aspergillus flavus, and Penicillium chrysogenum were more resistant to the basil oil nanoemulsion's elevated antibacterial activity (up to 20%)²⁰. At 1000ppm, the synthesized nanoemulsion significantly inhibits growth (64%–67%) compared to the synthetic fungicide Carbendazim. The solubility and antibacterial activity of silymarin were greatly increased when it was encapsulated by the nanocarrier as compared to when it was not entrapped (7.7-fold) by Lee et al²¹. Preparation of nanoencapsulated silymarin by using poly-gamma glutamic acid and water-soluble chitosan. Table 1 provides some recent research findings about nanoencapsulation as well as a summary of the approaches that are usually employed to encapsulate active compounds.

Techniques Involving Nanoencapsulation:

Encapsulation of active compounds is a moderate and effective approach to controlling drug release, improving the physical stability of the active ingredients, insulating them from environmental factors, restricting their volatility, enhancing their bioavailability, decreasing their toxicity, and improving patient compliance and accessibility²². Nanoparticles applied directly to the skin are used to support local therapy even when the fundamentals of penetration through the skin are still up for debate. It is generally accepted that topical drug delivery utilizing nanotechnology takes the nanoparticles into the deeper layers of the skin and typically does not allow them to reach the viable epidermis²³. However, improved particle penetration only happens in conditions where the creatine barrier is compromised, such as in aging or damaged skin²⁴. By acting as a reservoir, the use of nanoparticles enables a continual, progressive generation of the active components. Nanoparticles can also interact cellularly with the skin as adjuvants to enhance immunological reactivity for topical vaccination applications²⁵. The two alternative ways to give EOs are through oral intake and inhalation²⁶. The nano delivery systems are exposed to the mucosal lining of the nose, lung, oral cavity (sublingual and buccal cavity), stomach, and intestines by various channels²⁷. With the least amount of dosage, nanocarriers can prolong the therapeutic levels of EOs in the target tissues, increase their resistance to enzymatic degradation, and possibly even ensure the optimal pharmacokinetic profile under the circumstances²⁸. Despite the differences in their properties, the viscous, elastic, and sticky mucus layer that covers all mucosa tissues evolved to protect the body by swiftly encasing and removing hydrophobic molecules and undesirable substances²⁹. As a result, mucoadhesion defined as a nanoparticle's ability to stick to mucus while facilitating medication uptake becomes a useful tactic to extend the nanosystem's retention period and boost the absorption of the bioactive substances. Natural or artificial polymers that can interact with mucin through hydrogen bonds and hydrophobic interactions are commonly used to create contact. The electrostatic interface, which can be achieved by employing positively charged polymers like chitosan, is the most effective since mucin is negatively charged^30,31. The accumulation of nanosized delivery systems within the mucosal membrane is significantly influenced by the particle size, shape, and surface properties of the nanoparticles. It was found that nanocarriers with particle diameters around 50 and 300 nm, positive zeta potential, and hydrophobic surfaces have been more easily absorbed than their counterparts³².

Essential oils loaded Nanodelivery Systems:

Nano-delivery systems can be designed to have a variety of therapeutically useful properties, including localized, prolonged, and controlled release of drugs, (ii) deep muscle penetration due to their small size, (iii) cell membrane uptake and subcellular exploitation, and (iv) protection of therapeutic cargo at intracellular and extracellular levels. Many different materials and arrangements can be used to structure nanocarriers³³. Organic nanocarrier systems stand out for being highly biodegradable and biocompatibility and are divided into lipid- and polymer-based nanoparticles^34,35. Additionally, with the aid of uniquely designed machinery like electro-spinning, electro-spraying, and nanospray dryers, some nanoencapsulation of active compounds can be accomplished³⁶. Fig.1. provides a schematic illustration of EO nanosystem interfaces.

Fig. 1: Identical Nanoemulsion structure compared to other nanoparticles

Polymer-Based Nanocarriers:

Polymeric nanocarriers are colloidal solid particles that contain an active food ingredient surrounded by a polymeric matrix. They are categorized into two types: nanospheres and nanocapsules³⁷. The essential oil can be conjugated with the polymer's matrix, wall, or oily core. All of the synthetic polymers that have been created, including poly-cyanoacrylate polyvinyl alcohol, alkyl esters, polylactic acid, polylactic glycolic acid, and polyglycolic acid are biocompatible³⁸. The two groups into which the latter is usually divided include proteins and carbohydrates. Polysaccharides are substances that have a microbial or animal origin, such as xanthan gum and chitosan, as well as substances of a botanical source³⁹. They also include substances of soluble fiber origin proteins containing casein, soy proteins, gelatin, albumin, and so on. As natural biomaterials, polysaccharides are nontoxic, hydrophilic, stable, biodegradable, and safe. Additionally, polysaccharides have a wide range of natural resources at their fingertips and minimal processing costs⁴⁰. The probable methods by which EOs are released from carriers include dissolution, adsorption of the functional element that is adsorbed or surface-bound, transport through the matrix, matrix erosion via enzyme degradation, or a mixture of these reactions⁴¹.

Lipid-Based Nanocarriers:

Even though polymer-based nanoencapsulation techniques provide a wide range of benefits, their capacity for mass production is limited by the requirement to use various complex chemical or heat processes for monitoring. The high encapsulation effectiveness and low toxicity of lipid-based nanocarriers make them desirable for industrial manufacturing⁴². Lipid components, which are typically biodegradable and are thought to be available in the food and pharmaceutical industries, are used to develop lipid-based nanoencapsulation, such as nanoemulsions, solid lipid nanoparticles, and liposomes⁴³.

Micro and Nanoemulsions:

Microemulsions are homogeneously stable crystalline, transparent colloids of two immiscible liquids that are bound together by an interfacial surfactant layer⁴⁴. They are less expensive to produce than nanoemulsions, have droplet sizes larger than 500nm, and require less energy to form an emulsion since they happen spontaneously when aqueous, oily, and amphiphilic components mix. Microemulsions have several drawbacks, such as the need for high surfactant concentrations during synthesis, which could be dangerous when used in pharmaceutical applications⁴⁵. On the other hand, nanoemulsions can be made with a small range of surfactants⁴⁶. Nanoemulsions, are very fine oil-in-water dispersions with a tendency to rapidly separate into component phases. H however, may have rather good kinetic stability even over the past several years due to their incredibly small size and the significant steric stabilization between droplets. With droplet sizes ranging from 10 to 500nm, they are sometimes referred to as ultrafine emulsions, microemulsions, and sub-micrometer emulsions⁴⁷.

Liposomes:

One of the most explored colloidal delivery technologies is the liposome, which was first created for drug administration in the 1970s⁴⁸. One or more phospholipid-based bilayers are encapsulated by an aqueous core to form liposomes, which are vesicular self-assembling structures⁴⁹. In liposomes, one unilamellar vesicle (ULV), many concentric multilamellar vesicles, nonconcentric multivesicular vesicles, or a combination of these can be found (MVV). The sizes of these formations can range from extremely tiny (20 nm or less) to more or less huge (1 m or more). Due to the hydrophilic compartment and lipophilic palisade's presence, they are suitable as transporters for both hydrophilic and lipophilic chemicals⁵⁰. While bioactive substances are contained within liposomes, they can be protected from degradation, in the case of lipophilic molecules, lipid nanoparticle encapsulation can also enhance solubilization⁵¹.

Solid Lipid Nanoparticles:

Solid lipid nanoparticles (SLN) are small, lipid-based particles that are solid at ambient temperature or even body temperature. Waxes and triacylglycerols, among many other lipid and lipid-like substances, can make up for the lipid component⁵². These lipid particles are likewise quite tiny, measuring between 50nm to 1 m in diameter. Active compounds can be homogeneously solubilized either on the inside or exterior of the SLNs⁵³. The advantage of utilizing SLNs as a delivery system for lipophilic active components, it has been reported, that the solid particle size immobilizes the active components, boosting chemical protection, lowering leakage, and enabling prolonged release⁵⁴. Greater control over the physical and chemical stability of the conveyed ingredients is made possible by this physical property.

Equipment-Based Nanoencapsulation :

In most cases, it is required to utilize some reliable methods, such as grinders, homogenizers, mixing equipment, and so forth, to encapsulate bioactive substances. However, only uniquely designed equipment like electrospinning and electrospray can be employed to accomplish some unique needs, such as nanofibers and scaffolds made of nanofibers⁵⁵. Electrohydrodynamic methods include electrospinning and electrospray, which spin or spray a polymer solution with charged jets to produce fibers or particles⁵⁶. The capacity to carry heat-sensitive chemicals, the possibility of mass manufacture, and the adaptable size with a vast surface area of both technologies make the idea of using them both in food preservation appealing⁵⁷. Using the electrospinning technique, antimicrobial nanofibers have been developed to enclose bacteriocin in probiotics for the controlled release of drugs during food production and storage⁵⁸. Lipophilic and hydrophilic active compounds can be nanoencapsulated when nanoparticles are generated using the emulsion-diffusion technique by ultrasonication equipment (Fig. 2).

CONCLUSION:

EOs carry the potential to prevent and possibly cure various disorders. Nanotechnology is a cutting-edge method with practical benefits in medical and health research, enhancing chemical stability in several factors that might accelerate the degradation of active pharmaceutical ingredients in formulations. Nanoparticles are considered to be an effective concept that can address the main drawback of EOs to accomplish the preservation and functional impact with an enhancement in bioavailability. It is also a viable technique for limiting the optimal dosage of herbal-based active metabolites. However, the safety evaluation of nanomaterials must be carefully examined before marketing the products to ensure that customers are taking safe medication. Therefore, more innovative research is required in the area of economical, and reliable delivery systems to expand the industrial-level applicability domain of essential oils.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this manuscript.

ACKNOWLEDGMENTS:

Our study would not have been possible without the support and guidance of the SRM Institute of Science and Technology (SRMIST) and Chalapathi Institute of Pharmaceutical Sciences, (CLPT). We thank both of the institutions for their assistance throughout all aspects of our study.

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Received on 24.11.2023 Modified on 31.01.2024

Research J. Pharm. and Tech 2024; 17(8):3897-3902.

DOI: 10.52711/0974-360X.2024.00605

Encapsulation Techniques	Elucidation	Nanoencapsulation Examples
Emulsification	An emulsion is the outcome of the process of emulsification, which involves combining two immiscible liquids. Phase inversion temperature, emulsion phase inversion, and spontaneous nano emulsification are examples of bottom-up techniques. Top-down approaches include high-shear stirring, high-pressure homogenization, microfluidization, and ultrasonication¹².	Vitamin E encapsulated by Tween-80
Spray drying	The fundamental idea behind spray drying is to transfer the liquid into a drying chamber as small droplets that contain biologically active compounds, supply excess heat to the drying chamber, form microcapsules in the drying medium, and recover¹³.	curcumin encapsulated by chitosan/Tween 20
Freeze drying	The core premise behind freeze-drying is to first freeze the water existing in a solution or suspension before evaporating the water droplets¹⁴.	Fish oil encapsulated by poly-e-caprolactone and Pluronic F68
Complex coacervation	Coacervation is a widely used method for generating micro- and nanosystems. The primary stage is the production of an emulsion through electrostatic attraction between molecules with opposite charges to create the encasing structure¹⁵.	Folic acid encapsulated by casein nanoparticles
Electro-spinning and electro-spraying	A charged jet is used in two different electrohydrodynamic techniques to rotate or spray a polymer solution to create fibers or particles¹⁶.	Rosehip seed oil encapsulated by zein prolamine fiber
Extrusion	To promote gel formation and build a rigid and dense encapsulating system, the extrusion approach includes injecting a bio-based solution into another solution¹⁷.	Seed oils encapsulated by sodium alginate and high methoxyl pectin