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School of Pharmacy, Department of Pharmaceutics, Abhilashi University, Chail Chowk, Mandi, Himachal Pradesh, India.
Niosomes are vesicular systems designed for drug delivery, employing non-ionic surfactants and gaining considerable interest because of their stability, compatibility with biological systems, affordability, and capacity to encapsulate both hydrophilic and lipophilic therapeutic substances. In comparison to conventional liposomes, niosomes show enhanced chemical stability, simpler storage, and reduced manufacturing expenses. This article presents a comprehensive overview of niosomal formulation strategies, structural characteristics, and preparation methods, highlighting their role in optimizing drug delivery performance and therapeutic efficiency. Recent advances in ligand-targeted, stimuli-responsive, and surface-modified niosomes are critically discussed, emphasizing their potential for precise site-specific drug delivery and personalized medicine applications. Furthermore, the review summarizes major therapeutic applications. Key challenges related to large-scale production, long-term stability, regulatory approval, quality control, and clinical translation are also addressed. Overall, niosomes represent a promising nanocarrier platform for advancing targeted and controlled drug delivery in modern nanomedicine and for supporting the development of next-generation pharmaceutical formulations.
In the 1970s, niosomes were first made available to the cosmetics industry. These structures are non-ionic surfactant-based vesicles composed of one or more bilayers. Niosomes were frequently prepared using cholesterol and its derivatives. Non-ionic surfactant sheets spontaneously group together in the aqueous phase to create concentric bilayer vesicles that can hold hydrophilic and lipophilic materials [1]. Niosomes represent a novel drug delivery system (NDDS) aimed at supplying medication at a controlled rate that aligns with the body’s needs throughout the treatment of a disease, enhancing absorption and delivering the active ingredient to the intended site. The size of niosomes is incredibly small and microscopic. These particles have nanometric-scale diameters. Niosomes are more stable than liposomes, which are susceptible to oxidation and destruction because of their lipophilic properties. Niosomal formulations offer a more concentrated effect since their non-ionizing surfactants prolong their circulation [2]. Niosomal formulations live prolonged in blood circulation due to their non-ionic surfactant and hence their target action is more. Niosomes are tiny, microscopic organelles. The size of niosome is in nanometric scale which ranges about 20nm-100nm [3]. Drugs encased in niosomal vesicles offer multiple advantages, such as enhancing their physicochemical characteristics and stabilizing unstable medications. To sustain consistent charge within the formulation, niosomes often possess distinct charges on their surfaces, like (+) and (-), leading to flocculation or aggregation [4]. Usually, span-60 is non-inonic surfactant used to niosome formulation [5]. Niosomes do not need any specific conditions for their preparation and storage, unlike liposomes [6]. The technique for preparing niosomes is entirely reliant on the process used for liposome preparation. Often, during the formulation of niosomes, the drug remains unentrapped; this unentrapped drug is then separated using gel filtration or centrifugation techniques. A primary advantage of niosome formulation is that its non-ionic surfactants demonstrate greater stability than the phospholipids used in liposome preparation [7]. Different types of drugs can be targeted at specific sites by utilizing niosomes, owing to their multi-environmental structure [8]. Niosomes can be either uni-lamellar or multi-lamellar vesicles composed of non-ionic surfactants, cholesterol, and ionic surfactants to minimize formulation aggregation [9].
Currently, the aim is to merge biotechnology with nanotechnology by using green chemistry approaches that are safe for the environment in the production, characterization, and use of nanomaterials. Examples of such nanomaterials include gold and silver nanoparticles, nanovesicle systems, solid lipid nanoparticles, nanostructured lipid carriers, nanomicelles, dendrimers, polymeric nanoparticles, and mesoporous silica nanoparticles [10]. Moreover, recent developments in biotechnology, nanotechnology, pharmaceutical science, artificial intelligence, and genetic engineering are being applied in healthcare, leading to the emergence of a field known as nanomedicine [11]. Researchers are concentrating on developing novel nano-systems that regulate the release of various physiologically active materials, along with the production of nanomaterials. Nanocarriers and innovative drug formulations are essential for enhancing the bioavailability of drugs or natural remedies chemicals by accurately aiming at specific regions. Vesicular systems facilitate the movement of payloads to exact locations that enhance overall effectiveness [12]. In targeted drug delivery, a diverse range of carriers such as immunoglobulin, plasma protein, microspheres, synthetic polymers, erythrocytes, and liposomes are employed. However, liposomes and niosomes are still recognised and proven to be efficient drug delivery methods [13].
1.2 Types of Niosomes:
1.2.1 Based on the characteristics of lamellarity:
1. Small uni-lamellar vesicles (SUV): 0.025-0.05µm or 25-50nm [14].
2. Multilamellar vesicles (MLV): 0.5-10 µm [15]
3. Large unilamellar vesicles (LUV): 100nm [16]
1.2.2 According to the size:
1. Smaller niosomes: 100 nm - 200 nm
2. Larger niosomes: 800 nm – 900 nm
3. Bigger niosomes: 2 µm – 4 µm [17]
2. STRUCTURE AND COMPOSITION OF NIOSOME:
The HLB value of the surfactant is the main factor that influences the choice of surfactant for niosome preparation. The capacity of a surfactant to form vesicles relies entirely on its hydrophilic-lipophilic balance. To achieve suitable and compatible niosome vesicle formation, the surfactant's HLB value should range from 4 to 8.13. Niosomes are circular bilayer structures formed from non-ionic surfactants, which have the capability to create micelles. When surfactant concentrations exceed the critical micelle concentration (CMC), micelles are formed, but non-ionic surfactants can create a circular bilayer structure instead of micelles [18].
Niosomes have either a unilamellar or bilamellar vesicle structure. They are made up of non-ionic surfactants and different additives. The vesicles comprise both hydrophilic and hydrophobic components, enabling them to encapsulate and deliver hydrophilic and hydrophobic drugs to the destination [19].
Fig. 1: structure of niosome
The non-ionic surfactant forms a bilayer that evolves into a vesicle, leading to a hydrophobic membrane with a hydrophilic core inside the vesicle. The cholesterol in the niosomes will add stiffness and maintain the vesicle's permeability, whereas the charged molecule helps to stop vesicle clumping [20].
2.1 Composition of niosome:
Niosomes are vesicular structures made from non-ionic surfactants. Ionic surfactants are formed by the self-assembly of non-ionic amphiphilic molecules in aqueous solutions, resulting in closed bilayer structures [21]. Nonionic surfactants are the preferred surface active agents in vesicle formulation due to their greater stability, compatibility, and lower toxicity compared to anionic, amphoteric, or cationic counterparts. These versatile surfactants function as solubilizers, wetting agents, emulsifiers, and permeability enhancers [22].
Cholesterol possesses the unique capability to enhance lipid organization in liquid membranes while maintaining their flexibility and facilitating diffusion speeds. It offers mechanical stability and forms low permeability barriers in lipid membranes [23]. Cholesterol influences membrane permeability, rigidity, entrapment efficiency, ease of rehydration for freeze-dried niosomes, stability, preservation duration, and potential adverse effects. When combined with low HLB surfactants, cholesterol enhances the stability of vesicles, whereas an HLB value exceeding 6 encourages the formation of bilayer vesicles [24].
A charged molecule is included in the niosomal formulation to prevent niosome aggregation. If the formulation contains the same charge, particle repulsion occurs, preventing aggregation. Certain ionic surfactants with both positive and negative charges were incorporated into the niosomal formulation. Approximately 2.5-5 mole percentage of the charge molecule is needed to prepare niosomes [25].
2.2 Advantages of niosome:
Offer unique advantages as nanocarriers, including stability, ability for functionalization, making them ideal for achieving substantial tumor accumulation and cellular absorption for drug delivery [26]. Niosomes simplify the production and handling of dosage forms with pre-prepared dispersions. They improve the oral bioavailability and skin absorption of drugs [27]. Aqueous suspension of niosomes demonstrates a notable degree of patient compliance [28]. The method of producing niosomes does not require harmful solvents, making it appropriate for standard and large-scale production [29]. Niosomes demonstrate chemical stability, removing the requirement for specific storage or handling conditions [30]. In addition to being osmotically stable and functional but also enhance the stability of the encapsulated medication [31]. They can improve the penetration of medications through the skin [32].
2.3 Disadvantages of Niosomes:
The aqueous suspensions of niosomes have a short shelf life because of fusion, aggregation, and hydrolysis of the drugs they encapsulate [33]. The process of preparing multilamellar vesicles through extrusion and sonication methods is labor-intensive and necessitates specialized equipment for handling [34]. The drug loading capacity is inadequate [35]. Manufacturing requires specialized equipment. The medication leaks when contained [36]. The formulation requires a significant amount of time [37]. Unsteady physical condition [38].
3. METHOD FOR PREPARATION OF NIOSOME:
3.1 Thin film hydration or Hand shaking method:
The blend of vesicle-forming components, such as surfactant and cholesterol, dissolved in a volatile organic solvent in a round-bottom flask is subjected to solvent removal at room temperature (20°C). The dried surfactants are then rehydrated with an aqueous phase at temperatures between 0-60°C with gentle agitation, resulting in characteristic multilamellar niosomes [39].
Combine surfactant, cholesterol, and solvent
↓
Evaporate organic solvent at ambient temperature
↓
Moisten the dehydrated surfactant with water phase
↓
Create multilamellar niosomes
3.2 Ether injection method:
This technique consists of creating niosomes by gradually adding a surfactant solution that is dissolved in diethyl ether into heated water at 60°C. The resulting blend is subsequently injected through a gauze needle into an aqueous solution of the encapsulating substance, producing vesicles with diameters between 50 and 100 nm [40].
Dissolve the surfactant in diethyl ether
↓
Administer the solution into warm water (60 °C) with a 14-gauge needle
↓
Permit ether to evaporate, resulting in the formation of single-layered niosomes
3.3 Reverse phase evaporation method:
Cholesterol and surfactant are solubilized with ether and chloroform. When an aqueous phase that includes the drug is added to the mixture, ultrasound is applied at temperatures of 4-5 °C. The chemical is then mixed with a small amount of buffer salt to create a more sonic gel. At 40 °C, the organic solvent was extracted under low pressure large monolayers were created by heating the mixture in a water bath at 60 °C for 10 minutes after diluting the resulting suspension with phosphate-buffered saline (PBS) [41].
Combine cholesterol and surfactant in ether and chloroform.
↓
Sonicate the mixture at 5 °C and repeat following the addition of PBS
↓
Incorporate the drug solution into the blend
↓
Thin out the thick suspension using PBS
↓
Evaporate the organic solvent at 40 °C using low pressure
↓
Warm in a water bath at 60 °C for 10 minutes to create niosomes
3.4 Sonication Method:
For the preparation of niosomes using this technique, a drug solution in buffer is combined with a blend of surfactant and cholesterol in a 10ml glass vial. The mixture in the vial is subsequently exposed to probe sonication at a temperature of 60°C for 3 minutes. A titanium probe-equipped sonicator is utilized for this procedure. Probe sonication aids in creating niosomes, leading to the encapsulation of the drug inside the vesicles [42].
Medication in buffer + surfactant/cholesterol in 10ml
↓
The mixture is subjected to sonication for 3 minutes at 60°C with a titanium probe, resulting in the formation of niosomes.
3.5 Micro fluidization method:
Two fluidized streams advance through precisely defined microchannels and interact at ultra-high speeds inside the interaction chamber. A typical gateway is organized in a way that the energy provided to the system stays within the region where niosomes are formed [43].
Two extremely fast jets within interaction chamber
↓
Interference of a slender film of liquid in a microchannel.
↓
Formation of consistent niosomes
3.6 Multiple membrane extrusion method:
A blend of surfactant, cholesterol, and di-acetyl phosphate in chloroform is converted into a thin film through evaporation. The film is moistened with a water-based drug solution, and the resulting suspension is pushed through polycarbonate membranes arranged in a series for as many as eight passages. This is an effective technique for regulating niosome dimensions [44].
3.7 Bubble Method:
The foaming unit comprises a round-lined flask featuring three necks, which will be immersed in a very hot water bath to control the temperature. The primary and secondary openings feature the thermometer and water-cooled reflux, whereas the tertiary opening links to a nitrogen source. Cholesterol and surfactant are mixed in a buffer solution at pH 7.4 and heated to 70°C; this mixture is homogenized for 15 seconds with a high shear homogenizer, followed promptly by gas bubbling [45]
Table 1: Categories of Niosomes Created via Various Techniques and Their Benefits and Drawbacks:
|
Preparation Technology |
Categories of Niosomes |
Benefits |
Drawbacks |
References
|
|
Thin-film hydration method |
Multilamellar vesicles |
Basic technology
|
Removing organic solvents is challenging. |
46-47 |
|
Ether injection method |
Large unilamellar vesicles |
Basic technology |
Not suitable for heat-sensitive medications, organic solvent contamination. |
48-49 |
|
Sonication method |
Small unilamellar vesicles |
Eco-friendly approach, no organic solvent required |
Costly machinery and significant energy usage |
50-51 |
|
Reverse phase evaporation method |
Large unilamellar vesicle |
Elevated encapsulation effectiveness |
Potential remaining organic solvents |
52-53 |
|
Micro fluidization method |
Small unilamellar vesicle |
High level of consistency and repeatability |
Not appropriate for heat-sensitive medications, readily hydrolyzed and/or oxidized |
54-55 |
|
Multiple membrane extrusion method |
Small unilamellar vesicle |
Lowered polydispersity |
Heightened medication losses |
56-57 |
|
Bubble method |
Large unilamellar vesicle |
No organic solvents used |
Limited long-term storage durability |
58 |
Table2. Comparision of niosome with other nanocarriers:
|
Parameters |
Niosome |
Liposome |
SLNs |
|
Chemical stabilty |
High |
Low |
Moderate to high |
|
Physical stability |
Moderate |
Low |
High |
|
Biocompability |
High |
Very high |
High |
|
Cost |
Low |
High |
Moderate |
|
Control release |
Good |
Moderate |
Good |
4. APPLICATION OF NIOSOME IN DIFFERENT FIELD:
4.1) Protein/peptide transport:
Administration of protein and peptide medications via the oral route has consistently presented difficulties because of their susceptibility to deterioration from the acidic ecosystem and catalysts in the digestive tract gastrointestinal tract (GIT). Nevertheless, niosomes provide a shielding mechanism of action for these medications against proteolytic enzymes [59]. Niosomes coated with trimethyl chitosan were also created to improve the absorption of insulin for oral administration. Encapsulating these medications in niosomes can greatly enhance their stability and safeguard them from enzymatic breakdown in the gastrointestinal tract [60].
4.2) Niosomes as Transporters for Hemoglobin:
Hemoglobin is transported by niosomes. Similar to non-capsulated hemoglobin, these vesicles are readily permeable to oxygen and can modify the hemoglobin dissociation curve. The spectrum of niosomal suspension can be overlaid with that of free haemoglobin [61].
4.3) Transdermal Delivery:
Niosomes were studied for their potential to enhance drug absorption and minimize skin irritation while passing through the intact stratum corneum, in addition to functioning as a means for transdermal drug delivery. Researchers examined the uptake of ketorolac, a strong non-steroidal anti-inflammatory medication, into removed rabbit skin employing different proniosome gel formulations and Franz diffusion apparatus. The penetration of the drug and the delay time were notably improved to produce the proniosomes [62].
4.4) Niosomes for delivering drugs via the nasal route:
The nasal route is highly efficient for systemic drug administration. Its action begins very quickly. It offers several benefits compared to oral drug delivery systems, including the avoidance of hepatic first-pass metabolism and prevention of enzymatic or acidic degradation.
This path is more secured, non-intrusive, and additionally practical. This pathway allows the medication to effectively circumvent the Blood-Brain Barrier by utilizing the olfactory and trigeminal nerves route [63]. Bromocriptine Mesylate has minimal oral bioavailability due to its first-pass metabolism. To circumvent the bioavailability problem, instead of administering the drug orally, it can be administered via the nasal route by embedding the drug in niosomes to improve bioavailability [64].
4.5) Utilize in examining immune reaction:
Due to their immune selectivity, reduced risk, and increased stability, niosomes are being employed to investigate the nature of the immune response triggered by antigens. Nonionic surfactant vesicles have clearly demonstrated their ability to serve as adjuvants following parenteral administration with a variety of different antigens and peptides [65].
4.6) Ocular Medication Administration:
Proniosomes are utilized in ocular drug delivery, much like traditional niosomes. They can be utilized for drug delivery to the eye, offering controlled release, increased bioavailability, and extended presence on the ocular surface [66].
4.7) Vaccine delivery:
Vaccine Distribution: Proniosomes have demonstrated potential as transporters for vaccine distribution. They can encapsulate antigens, improving their stability and immunogenicity. Proniosomal vaccine formulations enhance the delivery of antigens to immune cells and promote a strong immune reaction [67].
4.8) Niosome for cancer therapy:
Niosomes represent a potential drug delivery method in cancer treatment as they assist in directing medications to cancer cells, extend the duration of treatment, enhance drug stability, and minimize severe side effects [68]. Different therapies have been researched to address acne. Cancer therapy poses numerous difficulties, such as untargeted delivery, limited drug efficacy duration, and the antitumor impacts of medications. Consequently, approaches to cancer treatment are evolving to enhance the efficacy and efficiency of therapies aimed at cancer cells [69].
4.9) Oral drug delivery:
Medications are delivered via this approach to tackle problems related to vulnerability to stomach acids and digestive enzymes, poor absorption, and varying medication bioavailability. As a result, new drug delivery systems like niosomes have been used to improve drug bioavailability. In another investigation, niosomes demonstrated enhancement of the poor and variable oral bioavailability of Cefdinir, which is classified as a class IV drug in the Biopharmaceutics Classification Scheme (BCS) [73].
4.10) Cosmetics:
L’Oreal was the first to link non-ionic surfactant vesicles with cosmetic use. In the 1970s and 1980s, L’Oreal created and obtained patents for niosomes. In 1987, Lancôme introduced “Niosomes,” their initial product. In the field of cosmetics and skin care, niosomes provide multiple advantages, such as enhancing the stability of encapsulated drugs, boosting the bioavailability of hard-to-absorb components, and improving skin penetration [74].
5. CURRENT DEVELOPMENTS AND INNOVATIONS IN NIOSOME TECHNOLOGY:
Recent developments in pharmaceutical nanotechnology have garnered substantial interest in niosomes as potential drug delivery systems. Niosomes are vesicular carriers at the nanoscale made mostly of non-ionic surfactants and cholesterol, emerging as adaptable platforms that can tackle issues linked to traditional drug delivery methods. Current studies have focused on improving their makeup, manufacturing methods, and medical uses, showcasing their versatility in numerous healthcare areas. These studies highlight the importance of niosomes in boosting drug delivery, facilitating regulated drug release, and increasing therapeutic effectiveness
Medication Administration in Neurodegenerative Diseases:
Recent progress in nanotechnology has resulted in the development of advanced and efficient drug delivery systems designed to carry therapeutic agents through the blood–brain barrier (BBB)[75]. These systems can be tailored to facilitate drug delivery either directly from the nasal cavity to the brain through the olfactory and trigeminal nerve pathways or indirectly through systemic circulation [76].
Niosomes in Delivery of Antibacterial Medications:
Niosomal drug delivery systems have shown considerable promise in antibacterial treatment, especially in tackling antimicrobial resistance. By transforming antibiotics into niosomal carriers, drug targeting and therapeutic efficacy at particular infection locations can be greatly improved. Investigations in this field have concentrated on assessing the physicochemical characteristics of non-ionic surfactants employed in niosome formulation. Span and Tween surfactants provide benefits like enhanced stability, wide compatibility, and formulation adaptability [77].
7. CONCLUSION:
Niosomes, vesicles made from non-ionic surfactants, provide a promising drug delivery method with benefits such as improved bioavailability, decreased toxicity, and heightened therapeutic effectiveness. Niosomes have become increasingly popular in recent years as drug delivery systems, particularly for medications with unstable properties, low solubility, or quick release. Broadening the use of non-ionic surfactants in this field may result in significant improvements in drug effectiveness and patient results. Additionally, advancements in niosome technology may gain from incorporating artificial intelligence to enhance their design and performance. This would enhance therapeutic results and facilitate wider clinical uses in multiple medical sectors, such as cancer treatment, gene transfer, and vaccine distribution. Moreover, niosomes have demonstrated significant promise as drug delivery systems in cancer studies. Niosomes can be employed as prospective drug carriers for hazardous anti-cancer, anti-infective, anti-AIDS, anti-inflammatory, antiviral, and other treatments, improving their bioavailability and targeting qualities while reducing their toxicity and adverse effects. Niosomes have great potential as sophisticated drug delivery systems, but further study is required to address issues with drug loading, stability, and scalability.
REFERENCES
Usha Kumari, Dr. Abhishek Soni, Nishant Sharma, Pardeep, Niosome as Next-Generation Nanocarriers for Stable, Controlled and Targeted Drug Delivery: A Comprehensive Review, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 5, 5909-5921. https://doi.org/10.5281/zenodo.20344174
10.5281/zenodo.20344174