INTRODUCTION:

Lipid-based carriers, particularly in intranasal drug administration, can improve the bioavailability and solubility of drugs with low water solubility¹. However, drugs with low water solubility face challenges in administration due to irregular and unpredictable absorption². To address this, various techniques have been developed to improve solubility, including drug carrier systems, solvent composition, amorphization, chemical modification, crystal engineering, and particle size reduction³. Despite these efforts, low-soluble drugs often suffer from decreased bioavailability and therapeutic efficacy due to premature elimination by the gastrointestinal tract⁴. Regulatory bodies such as the FDA and EMA have recognized these challenges and are setting standards to ensure the quality of drug delivery systems for such substances.

Nanotechnology has emerged as a promising approach to enhance dissolution, solubility, absorption, and bioavailability of poorly soluble medications⁵. Hydrophilic monomers and polymers exhibit hydration levels of up to 90%, making them more favorable choices for improving the solubility of pharmaceuticals with low solubility⁴. Among various nanocarriers, emulsomes stand out due to their unique structure, which combines the benefits of both emulsions and liposomes. Unlike other carriers, emulsomes have an inherent ability to encapsulate hydrophobic drugs efficiently, enhancing their solubility and stability. This is particularly advantageous for drugs like curcumin and silybin, which are known for their poor water solubility¹. Emulsomes offer a distinct advantage over traditional carriers, such as solid lipid nanoparticles (SLNs) and liposomes, by providing a more versatile platform for improving the delivery of hydrophobic drugs through enhanced encapsulation efficiency and controlled release properties. Their ability to improve drug solubility and protect sensitive compounds makes emulsomes a significant advancement in the field of nanocarrier-based drug delivery.

Emulsomes as promising carriers for nasal drug delivery:

Emulsomes enhance a drug's solubility and bioavailability. Due to their unique properties, they work well with drugs that are not highly soluble in water. With the use of emulsome-based technology, toxicity problems brought on by drug localization in target cells can be mitigated. Compared to liposomes, emulsomes provide controlled and prolonged drug release, lasting up to 24hours. Their size is nanoscale, and they have the ability to change pharmacokinetics and stop multidrug resistance. Emulsomes offer a high medication loading capacity and are less costly than conventional lipid formulations. They may consist of 50–250nm-diameter stable lipid particles¹.

Structure and stability of emulsomes:

Emulsomes are highly optimized and stable preparations made of phospholipid, solid lipids (Triglycerides), cholesterol, and charge inducers⁶. They can be prepared efficiently using various nanoparticle techniques and aim to achieve particle size within 10–1000nm while maintaining formulation stability⁷. Emulsomes are lipid-based formulations that exhibit enhanced stability in suspensions compared to liposomes. The shell's stability is due to its multilamellar structure and solid lipid core. Storage temperature significantly impacts the nanocarrier's stability. Emulsomes based on tripalmitin remain stable for at least three months when stored at 4°C⁸. However, storing at 20°C and 37°C may lead to depletion of surface charge and particle clumping⁹. Trehalose or sucrose can be used to freeze-dry emulsomal formulations, allowing extended storage periods at -20°C¹⁰. Emulsomes are known for their ability to maintain biophysical properties, such as size, zeta potential, and drug retention over time¹¹. They have practical value in clinical practice due to their superior stability in suspensions compared to liposomes¹². Accurate measurement of zeta potential in electrostatically stabilized vesicles is crucial for understanding dispersion and aggregation phenomena ^13,14.

Fig. 1: Structure of Emulsome

Selection of lipid and surfactant components:

Solid lipids and surfactants are examples of hybrid lipid components that can improve the structural stability and drug loading capacity of emulsomes, prolonging their half-life in the nasal cavity and speeding up drug transit through the nasal mucosa¹. The pharmacological properties, type of lipid material, and concentrations of charge inducers, phospholipids, triglycerides, and drug candidates are factors that influence the formulation of emulsomes. To control drug release, trapping efficiency, and particle size, the formulation can be adjusted¹⁵. For lipid-based vesicles to be effectively encapsulated, the right concentrations, biodegradability, biocompatibility, and non-toxicity are required¹⁶. Nanocarrier stability is also influenced by lipid physicochemical properties and storage temperature. Phospholipid layers are one type of surfactant that can help stabilize particles and enhance drug trapping in emulsomes. This layer can be covered by concentrated bilayers containing aqueous materials and water-soluble medications. While a negative charge stabilizes particles and increases the zeta potential, a positive charge enhances particle dispersion. Depending on the temperature and degree of hydration, phosphatidylcholine, a surfactant with high levels, forms lamellar, micelle, or bilayer sheets. Lecithin's potent hydrophobicity makes it a popular choice for amphipathic surfactant applications. Drug entrapment efficiency is increased, and drug leakage is reduced when cholesterol stabilizes the outer phospholipid layers and enhances fluidity-buffering activity. However, excessively high cholesterol levels may hinder drug trapping in vesicles¹.

Fig. 2: Composition of Emulsome

Methods for drug incorporation in emulsome:

Emulsomes are prepared using various nanoparticle formulation techniques to achieve particles within the size range of 10-1000 nm and maintain stability. The preparation typically occurs within a transition temperature of 25-45°C, with organic solvents like n-hexane, dichloromethane, and toluene used for lipid film incorporation^17,18.

1. Lipid Film Formation: Lipid components and drugs are dissolved in an organic solvent, which is then evaporated to form a dry lipid film. The film is hydrated with phosphate buffer, leading to emulsome formation. This method requires precise temperature control to ensure proper hydration and drug encapsulation.

2. Reserve Phase Evaporation: An oil-in-water emulsion is created using sonication or mechanical techniques, followed by solvent evaporation. This method yields 60-65% encapsulation efficiency but may be prone to instability due to fluctuations in sonication or evaporation conditions.

3. High-Pressure Extrusion: The lipid-drug mixture is forced through a filter membrane under high pressure, forming unilamellar vesicles. Microfluidization is used to refine vesicle size, requiring careful control of extrusion pressure and membrane size for reproducibility.

4. Cast Film Method: Phospholipids and triglycerides are combined in an aqueous solution, forming a dry lipid film upon solvent evaporation. The drug is added to the film, ensuring even distribution and encapsulation.

5. Detergent Removal: Detergents solubilize lipids into micelles, which encapsulate the drug. The detergent is removed through dialysis, forming stable emulsomes.

Reproducibility Considerations: Consistent lipid composition, solvent evaporation, hydration conditions, and detergent removal protocols are essential for reproducibility. Particle size, zeta potential, and encapsulation efficiency should be regularly assessed to ensure consistent results.

Fate of emulsome in nasal route:

Intranasal drug delivery (IND) is recommended for emergency situations and local indications like pain management and seasonal rhinitis. However, excipients may reduce safety. Interest in IND is growing for CNS applications, including neurodegenerative diseases¹⁹. Experimental procedures like in vivo imaging and quantitative analysis are needed²⁰. Nanotechnology can resolve physiological factors for CNS treatments, focusing on reducing neurotoxicity, increasing BBB permeability, and enhancing drug-trafficking effectiveness²¹. Nanoemulsions have shown potential for increasing dosages via intranasal delivery²². The nasal cavity is a complex structure that plays a crucial role in respiratory physiology and facial attractiveness. It consists of three main layers: the interior lining, the structural framework, and the soft tissue envelope. The external nose is a pyramid-shaped structure with dimensions varying based on sex, age, and race²³. Soft tissue structures vary in thickness along the dorsum²⁴. Lipid-based nanocarriers are ideal for medicine targeting due to their stability and resistance to degradation. Intraperitoneally injected nanocarriers can bypass the blood-brain barrier, delivering drugs directly into the brain, promising for pain, inflammation, and neurodegenerative illnesses like Parkinson's and Alzheimer's. Intranasal emulsome drug delivery could benefit drug development¹.

The nasal mucosa, a part of the blood vascular network, allows for quick medication absorption and direct administration. Emulsomes, lipid-based nanoparticles, can improve medication absorption through the nasal mucosa, reducing the need for frequent administration¹. Emulsomes can pass through human mucus secretions and maintain mucoadhesive properties²⁵. Mucociliary clearance is crucial for drug absorption, and toxicological studies should consider the effects of excipients and active ingredients on this process²⁶. Techniques like ciliary beat frequency monitoring and in vivo investigations can help in toxicological screening and ensuring medication safety²⁷. Studies using fluorescent microspheres and dual-radioisotope labeling have shown strong linear associations in predicting nasal medication absorption²⁸.

Techniques for evaluating emulsome characteristics:

The study evaluated emulsome characteristics using transmission electron microscopy (TEM), polydispersity index, zeta potential measurement, and particle size using Zetasizer NanoZS. The impact of independent variablses on particle size varied, with a stronger connection between predicted and actual value²⁹. Particle size was significantly affected by factors such as PC concentration, lipid ratio, and TMC content¹⁶. The study also examined drug entrapment efficiency using size exclusion chromatography and high performance liquid chromatography³⁰. Differential scanning calorimetry (DSC-60) was used to calculate the heat required to raise a sample's temperature²⁹^,³¹. The study also conducted a permeation study of EH from prepared mucoadhesive emulsomes through the nasal mucosa using a Franz diffusion apparatus, phosphate buffered saline medium, and sheep nasal mucosa as a membrane¹⁶. Stability studies showed that both Phospholipid: lipid and drug: T. lipids increased the permeability coefficient due to stable vesicles and higher vesicle sizes²⁹. In vitro drug release studies were conducted using the dialysis membrane sac technique³⁰.

Applications of emulsomes:

Emulsomes are used for drug targeting, increasing bioavailability of lipophilic drugs, and in cancer treatment. They can be coated with ligands like O-Palmitoyl Mannan or O-Palmitoyl Amylopectin, allowing the reticulo-endothelial system to recognize opsonin, which can cure liver and spleen infections^{13,32, 33}. Emulsomes also enhance the bioavailability of lipophilic medicines, such as methotrexate and curcumin, and are used in carrier therapy for leishmaniasis and fungal infections^10,34,35. Emulsomes also improve the immunogenicity and antigenic integrity of mucosal vaccines, reducing joint disease severity and stimulating robust IgG and IgA responses^36,37.

CONCLUSION:

Emulsomes are a promising drug delivery system for poorly water-soluble drugs, especially for nasal administration. Their lipid-based structure combines the advantages of emulsions and liposomes, offering enhanced drug solubility, improved bioavailability, and controlled, prolonged release. This makes them ideal for drugs like curcumin and silybin, which are challenging to deliver effectively. Emulsomes bypass gastrointestinal degradation, increase therapeutic efficacy, reduce side effects, and provide excellent stability and drug loading capacity. They also enable targeted delivery, such as to the brain, and can modify pharmacokinetics for better therapeutic outcomes. However, challenges exist, such as the need for careful formulation optimization to balance stability, drug release, and nasal mucosa interaction. Stability at varying temperatures, potential toxicity of surfactants, and premature drug release are concerns that require attention. Furthermore, emulsomes' interaction with the nasal mucosa and the need for rigorous clinical testing pose additional hurdles before widespread clinical use. Despite these challenges, emulsomes hold significant promise in enhancing drug delivery, particularly in nasal and brain-targeted therapies. Looking ahead, the future of emulsome research is incredibly promising. As advancements in formulation technologies continue, emulsomes could revolutionize the delivery of poorly water-soluble drugs, particularly for complex diseases like cancer, neurodegenerative disorders, and even in vaccine delivery. Ongoing research focused on optimizing encapsulation efficiency, refining release profiles, improving their stability under various conditions, and enhancing their safety and biocompatibility will play a critical role in overcoming current limitations. With these innovations, emulsomes could become a cornerstone of modern drug delivery, enhancing therapeutic outcomes, minimizing side effects, and improving patient compliance. The next decade holds immense potential for emulsomes to redefine how challenging drugs are delivered, making them a key area of research in the future of personalized and targeted medicine.

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Received on 25.01.2025 Revised on 13.05.2025

Accepted on 12.07.2025 Published on 16.03.2026

Available online from March 18, 2026

Research J. Pharmacy and Technology. 2026;19(3):1454-1458.

DOI: 10.52711/0974-360X.2026.00209

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