Anuradha College of Pharmacy, Chikhli, Maharashtra 443201
Niosomes are innovative vesicular delivery systems composed of non-ionic surfactants and cholesterol, which assemble to create stable bilayer structures that can encapsulate both hydrophilic and lipophilic drugs. Due to their superior chemical stability, simplicity in formulation, and lower production costs compared to traditional liposomes, they have attracted considerable interest as a flexible drug-delivery solution. This review details the formation of these vesicles and examines how factors such as surfactant type, cholesterol content, surface charge, and functional coatings influence vesicle size, bilayer count, drug-loading capacity, and release characteristics. Significant preparation methods—including thin-film hydration, reverse-phase evaporation, microfluidic processes, and proniosomal systems—are explored with a focus on their practicality, scalability, and compliance with regulatory standards. In various delivery routes such as ocular, oral, Transdermal, nasal, pulmonary, and targeted cancer applications, niosomal formulations consistently shows improved penetration, extended retention time, and enhanced therapeutic efficacy compared to traditional drug formula. However, challenges remain, assuring long-term stability, controlling protein-corona advancements, and achieving method standardization. Overall, niosomes represent multifaceted and promising platform for improving the efficacy of numerous therapeutic agents.
In recent years, drug-delivery research has steadily shifted toward systems that can deliver medicines more precisely, more safely, and with better therapeutic outcomes. Among the different vesicular carriers explored, niosomes have seen as one of the most acceptable and sustainable options. These vesicles are formed when non-ionic surfactants combine with cholesterol to create a adaptable, stable bilayer structure capable of entrapping a wide variety of drugs[1,2,3].
Because of this structure, release them in a controlled way, making them beneficial for both hydrophilic and lipophilic agents. A major reason of growing interest in niosomes is their practical benefits over liposomes. While liposomes were one of the nascent vesicular delivery systems, their phospholipid elements are likely to oxidation and can be costly to work with. Niosomes, on the other hand, offer improved chemical stability, are easier to formulate, and allow more freedom in adjusting robustness size, rigidity, surface charge, and drug-loading capacity. These modifiable features give researchers substantial control over how the drug behaves inside the body, it stays in circulation, and how efficiently it reaches the target tissue[4].
Because of these benefits, niosomes have been investigated for a wide range of therapeutic applications—from cancer therapy and transdermal delivery to ocular, pulmonary, and even vaccine-related uses. Reduce unwanted side effects, and maintain longer drug levels at the site ,Parallel to this progress, formulation techniques have also become more advanced. Modern approaches such as thin-film hydration, reverse-phase evaporation, microfluidic systems, and proniosomal technology have helped improve batch uniformity and targeting issues related to scale-up and industrial viability
Still, niosomes have some limitations. Concerns such as vesicle accumlation, leakage of the entrapped drug during storage period, and the lack of standardized manufacturing guidelines continue to challenge researchers. However,continuos advancement on surfaceengineered niosomes, encapsulation systems, and hybrid vesicles is consistently elevating their stability and advancing their potential clinical significance[5,6].
Overall the advancement in niosomal research strongly indicates that these vesicles are more than just an substitution to traditional carriers—they shows dynamic and evolving platform that can significantly improve the therapeutic performance of many drugs. With continued improvements, niosomes are likely to play major role in the development of modern, patient-oriented drug-delivery systems.
COMPOSITION:
Non-ionic surfactants are most important part of Niosomes Common examples include Span (20, 40, 60, 80), Tween (20, 40, 60, 80), Brij series, and polyoxyethylene alkyl ethers. These molecules naturally assemble into multilamellar manner.Their hydrophilicity and lipophilicity balance (HLB), chain length, and saturation level play important role in evaluating the vesicle’s size, number of layers, drug-loading capacity, and release profile. Surfactants with longer saturated chains, such as Span 60, generally create more stable bilayers and higher drug encapsulation[8].
Cholesterol is added with the bilayer to make the vesicles more robust and stablized. By inserting itself between surfactant molecules, cholesterol decrease leakage of the encapsulated drug and protect the vesicles from mixing together. The perfect balance of cholesterol is mandatory very small quantity can make vesicles fragile, while large quantity can decrease drug encapsulation efficiency[9].
Dicetyl phosphate (negative charge) or stearylamine (positive charge) can be included to improve stability.Electrostatic repulsion between vesicles is created due to this agents,Which helps to shield aggregation during storage period or in biological fluids[10,11].
Chitosan, PEG, carbopol, or hyaluronic acid are some polymers which in small quantity can use to coat the vesicles for incorporating special properties. Mucoadhesion can be increase by this coating, extend residence period, shield the vesicles from early degradation, and help in targeted drug delivery system. Such surface-modified niosomes are particularly useful for ocular, nasal, or systemic delivery[12].
Hydrophilic drugs are encapsulated into the water phase of the vesicles, while lipophilic drugs are added into the bilayer. pH, ionic strength, and buffer composition are some factors that influence vesicle formation, stability, and drug-encapsulation efficiency[13,14,15].
In certain preparation methods, solvents like as chloroform, ethanol, methanol, or diethyl ether are added to dissolve the surfactants and cholesterol. During the process these solvents are removed and not present in the final formulation[16,17].
CHARACTERIZATION:
Characterizing niosomes is essential for understanding their structural and physicochemical properties, and activity profile, all of which directly effect their therapeutic activity. Morphology, distribution, and polydispersity index (PDI) are commonly measured using dynamic light scattering (DLS), as these factors affects stability, drug delivery efficiency, ability oftissue penetration.Zeta potential gives information on colloidal stability and surface stability where higher absolute values generally shows lower accumulation and better storage property.Morphology and bilayer structure are examined using techniques such as transmission electron microscopy (TEM), scanning electron microscopy (SEM), or cryo-TEM, confirming vesicle formation, uniformity, and lamellarity.The entrapment efficiency (EE%) is determined by separating free drug from encapsulated drug through ultracentrifugation method or dialysis, accompanied by spectrophotometric or chromatographic analysis, which shows the niosome’s capacity to entrap hydrophilic or lipophilic molecules.In-vitro release studies using membrane diffusion system method.shows release profiles and help Antici6 in-vivo profile. Bilayer properties, such as stability and permeation properties, can be studied using differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR), showing interactions between surfactants and cholesterol.At the end, stability studies, conducted under both short term as well as long term conditions, tracking vesicle stability, leakage, and accumlation over time. Overall, these characterization methods shows the essential quality character of niosomes, Highlighting their ability as potent and promising vesicular drugdelivery system for improved therapeutic efficacy[7].
METHODOLOGY:
The systematic Advancement and development of niosomes as advanced vesicular drug delivery systems consist of multiple critical steps,consist careful material selection, suitable formulation design, precised preparation method, drug encapsulation, and optimization processes, all having goal to ensure enhanced therapeutic effect and reproducibility and stability of formulation.
Niosomal vesicles are mostly composed of non-ionic surfactant.Aditionally components such as Spans, Tweens, or Brijs, are added with cholesterol to provides stabilized bilayer and retain membrane rigidity. Selection of Surfactant is guided by chain length hydrophilic–lipophilic balance (HLB), phase transition temperature, and compatibility with the therapeutic components. Additionally charged molecules like lipids or polymeric coating is also incorporated to enhance mucoadhesive potential colloidal stability, and site-specific targeting. Depending on the physicochemical properties both hydrophilic and lipophilic drugs can be encapsulated within the aqueous core or lipid bilayer, solubility, and intended route of administration.
Some well-established techniques are used for niosome fabrication:
Thin-Film Hydration (TFH):
In an organic solvent Surfactants and cholesterol are incorporated to form a thin lipid film and Hydration with an aqueous drug solution over the surfactant transition temperature produces bilayer vesicles, which can be restructured by sonicator or extrusion to achieve uniform size distribution.
Reverse-Phase Evaporation (REV):
Surfactant cholesterol solutions in organic solvents are emulsified with drugs aqueous solutions. Gradual removal of the organic phase results in single layer vesicles with increased drug encapsulation efficiency and maintain better size control.
Ether/Organic Injection:
The surfactant solution is introduced via injected into an aqueous drug phase, allowing vesicle formation when the solvent evaporates, providing easy and labscale method.
Proniosome Approach:
Surfactant-coated dry powders get converted into niosomes upon hydration, enabling improved storage stability, ease during handling, and on-demand vesicle formation.
Advanced Techniques:
High-pressure homogenization Microfluidization, or membrane contactor methods provides controlled production of uniform vesicles with narrow size distribution and high reproducibility, beneficial for industrial and clinical applications.
Drug encapsulation can be obtained during vesicle formation (passive loading) or during active strategies such as pH- or ion-gradient methods for ionizable drugs. Entrapment efficiency is determined by separating free drug from encapsulated drug, generally by ultracentrifugation method or dialysis method, followed by Analysis such as spectrophotometric or chromatographic analysis. Systematic optimization of surfactant type, cholesterol ratio, hydration conditions, and after processing parameters assures the formation of niosomes with intended vesicle size, polydispersity index, high encapsulation efficiency, and monitized release profiles, By increasing therapeutic effect and formulation stability.
CONCLUSION:
Niosomes vesicular systems composed of non-ionic surfactants and cholesterol provides a versatile, cost friendly substitute to phospholipid-based components, Achieve chemical stability with adjustable control over size, bilayer structure, surface properties, and encapsulation efficiency. Progress in preparation (thin-film hydration, reverse-phase evaporation, proniosomes, and microfluidic/homogenization approaches) have enhanced consistency enhanced retention time, and preclinical studies across ocular, transdermal, oral, nasal, pulmonary, and anticancer applications consistently shows increased penetration, prolonged retention, and betterment in therapeutic effectivity . Remaining challenges to clinical scale include long-term physical and chemical stability, drug leakage, protein-absorption effects in vivo, and the absence of standardized manufacturing and regulatory processes. Focused research on advance surface engineering, standardized characterization approach, comprehensive in vivo and pharmacokinetic evaluation and industry-oriented scale-up will be mandatory to approve niosomal formulations from promising laboratory to approved clinical therapeutics.
REFERENCE
Dhanashri Tikar, Ashwini Awasare, Arati Kolhal, Disha Jadhao, Anjali Gawai, R.A. Ingle, K. R. Biyani, Niosomes: A Promising Vesicular Drug Delivery System for Enhanced Therapeutic Efficacy, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 11, 3890-3895. https://doi.org/10.5281/zenodo.17700496
10.5281/zenodo.17700496
