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School of Pharmaceutical Sciences, RIMT University, Mandi Gobindgarh, Punjab, 147301
Dermatological disorders such as acne, psoriasis, eczema, and fungal infections remain major global health concerns, often requiring long-term therapy. Conventional topical formulations face significant challenges, including poor skin penetration, rapid drug degradation, and low patient compliance. To overcome these limitations, nanocarrier-based delivery systems have emerged as promising alternatives. Among these, niosomes—vesicular carriers composed of non-ionic surfactants and cholesterol—have attracted considerable attention due to their biocompatibility, stability, and ability to enhance dermal drug delivery. Recent studies demonstrate that niosomes can improve skin retention, sustain drug release, and protect labile molecules, making them highly suitable for dermatological applications. This review highlights the structural aspects, preparation methods, and advantages of niosomes, with a particular focus on their role in treating various skin conditions. Comparative insights with other vesicular systems, current challenges, and future directions for clinical translation are also discussed. Overall, niosomes represent a versatile and effective platform with strong potential to advance the field of topical and transdermal drug delivery.
Dermatological disorders, including acne, psoriasis, atopic dermatitis, fungal infections, and others, impose significant burdens worldwide in terms of morbidity, psychological impact, and health?care costs. Conventional topical therapies such as creams, ointments, lotions, and gels are often limited by poor drug penetration across the skin barrier, rapid drug degradation, low drug retention, frequent dosing requirement, and poor patient adherence (1,2,3).
The skin’s stratum corneum (SC) is the principal barrier to drug permeation; its lipid-rich intercellular matrix particularly restricts hydrophilic or large molecule penetration (4,5). Moreover, many active pharmaceutical ingredients are chemically unstable or suffer from low solubility, limiting their formulation into conventional vehicles without loss of efficacy or premature degradation (6,7). Additionally, factors such as irritation potential, cosmetic acceptability, and vehicle?related discomfort can further reduce patient compliance (8).
To overcome these limitations, advanced drug delivery systems have been pursued. Among these, nanocarriers (including liposomes, solid lipid nanoparticles, nanoemulsions, polymeric nanoparticles, micelles, ethosomes, etc.) have shown promise for enhancing skin permeation, improving drug stability, enabling sustained or controlled release, and achieving targeted delivery (9,10,11). Reviews have reported that nanoparticles, when properly designed (size, charge, hydrophobicity, surface functionalization), can enhance permeation through the SC, accumulate in specific layers of skin (epidermis, dermis), and reduce systemic side?effects while improving local therapeutic outcomes (12,13,14).
Vesicular systems in particular — such as liposomes and niosomes — offer further advantages. Niosomes are non?ionic surfactant based vesicles, often combined with cholesterol, which are more stable, less expensive, and can be easier to scale than some lipid?based vesicles. Their bilayer structure allows entrapment of both hydrophobic and hydrophilic actives, protecting labile molecules from degradation, and enabling sustained or controlled release (15,16).
Film?forming systems (films, film?forming gels, patches, etc.) are another promising vehicle class. They provide continuous contact with the skin, reduce loss of active ingredient (by evaporation or rubbing off), and can improve patient adherence by reducing dosing frequency and improving cosmetic acceptability (17,18). However, despite many promising preclinical studies, translation to clinical practice remains limited. Many nano?formulations face challenges in reproducibility, scale?up, regulatory approval, stability under storage conditions, skin irritancy, and cost of goods (19,20). There is also a lack of comprehensive comparative studies among different vesicular systems, especially in context with herbal bioactives. With this background, the present review focuses on niosomal drug delivery systems in dermatological applications, exploring their fundamentals, advantages, current applications (including anti?acne therapy), challenges, and future directions.
2. Niosomes: Fundamentals
2.1 Structure and Composition
Niosomes are vesicular, bilayered nanocarriers made primarily of non-ionic surfactants and cholesterol, often with charge-inducing agents and a hydration medium to stabilize the vesicle and tune its properties (21,22,23). The bilayer structure consists of hydrophobic tails inward, hydrophilic heads outward, forming an aqueous core that can encapsulate hydrophilic actives, while hydrophobic compounds may be embedded in the bilayer membrane (22,23).
Key components include:
Other structural parameters include vesicle size (small unilamellar, large unilamellar, multilamellar), lamellarity, bilayer thickness, surface charge (zeta potential), and the encapsulation capacity. These properties are significantly affected by the choice and ratio of surfactant:cholesterol, as well as preparation method (22,29).
2.2 Methods of Preparation
Several methods are used for preparing niosomes; each has its advantages and limitations depending on the active molecule, desired vesicle size, encapsulation efficiency, scale, and cost. Important methods include:
|
Method |
Principle / Steps |
Advantages |
Limitations |
|
Thin-film hydration (hand-shaking) |
Surfactant + cholesterol dissolved in organic solvent → solvent evaporated to form thin film → film hydrated with aqueous phase containing drug to yield vesicles; often followed by sonication or extrusion to reduce size. (22,23,30) |
Good entrapment, relatively simple; lamellarity adjustable; widely used in lab scale. (22,30) |
Use of organic solvents; possible residual solvent; size control less precise; lamellarity may lead to larger vesicles. |
|
Reverse-phase evaporation |
Organic phase (surfactant + cholesterol + maybe drug) emulsified with aqueous phase, then organic solvents removed under vacuum leading to formation of large unilamellar vesicles (LUVs). (22,31) |
Higher encapsulation of hydrophilic drugs; suitable for a variety of actives. |
More complex; organic solvent removal critical; possible solvent residual; scale-up challenging. |
|
Ethanol (or solvent) injection |
Injection of surfactant + cholesterol solution in ethanol (or other solvent) into aqueous phase → spontaneous vesicle formation. (22,32) |
Simpler; faster; fewer steps; good for small unilamellar vesicles. |
Organic solvent use; maybe smaller encapsulation efficiency; size and polydispersity somewhat harder to control. |
|
Sonication / Probe or Bath Ultrasonication |
After initial hydration or mixing, applying ultrasound (bath or probe) to reduce size and polydispersity. (22,33) |
Produces small size vesicles; useful for reducing multilamellarity; lower cost equipment. |
Heat generation may degrade sensitive drug; possible damage to structure; limited control over exact size distribution. |
|
Microfluidics / Controlled mixing methods |
Using microfluidic channels or flow-focussed mixing to control vesicle formation via precise control of flow rates and mixing. (22,34) |
Excellent size control; reproducibility; amenable to scale-up; lower polydispersity. |
Require specialized equipment; initial cost; optimization needed per formulation. |
|
Bubble method |
Dispersing surfactant + cholesterol in buffer, then bubbling nitrogen gas or another inert gas, sometimes with heating, to form vesicles (solvent-free or low solvent). (22) |
Fewer/without organic solvents; simpler; potentially more biocompatible. |
Less researched; scalability and reproducibility less established; control over size/polydispersity limited. |
|
Heating method |
Heating mixture of surfactants, cholesterol, and drug/hydration medium to above gel-transition temperature or melting point, sometimes with agitation, to form vesicles. (22) |
Simpler; applicable when drug is heat stable; fewer solvents; can be low cost. |
Not suitable for heat-sensitive actives; potential degradation; size may be large; stability issues. |
2.3 Key Factors Affecting Niosome Properties
Some of the critical formulation/processing variables include:
3. Advantages of Niosomes in Dermatological Applications
Niosomes offer several compelling advantages for skin drug delivery, which make them particularly well-suited for treatments like acne, inflammatory dermatoses, cosmetic therapy and anti-aging. Key advantages include:
3.1 Enhanced Skin Penetration and Retention
3.2 Improved Stability and Protection of Labile Actives
3.3 Controlled / Sustained Release
3.4 Biocompatibility, Low Toxicity and Cost-Effectiveness
3.5 Versatility in Encapsulation of Different Types of Actives
3.6 Cosmetic Acceptability, Aesthetics and Patient Compliance
4. Comparative Insights
Niosomes are often compared with other vesicular drug delivery systems such as liposomes, transfersomes, ethosomes, and solid lipid nanoparticles (SLNs). Their performance differs across parameters such as skin penetration, stability, drug release, and cost.
4.1 Niosomes vs Liposomes
Niosomes are generally more chemically stable than liposomes, since non-ionic surfactants are less prone to oxidative degradation compared with phospholipids (41). Liposomes may provide better fusion with skin lipids due to their phospholipid composition, but they are expensive and less stable on storage (42). Some studies report liposomes offer higher skin flux, while niosomes tend to retain drugs in the epidermis and superficial dermis (42).
4.2 Niosomes vs Transfersomes, Ethosomes, and SLNs
Transfersomes, due to their high deformability, can squeeze through narrow intercellular channels in the stratum corneum, often outperforming niosomes in penetration depth, though with stability concerns (43). Ethosomes, enriched with ethanol, enhance penetration but may cause irritation; in contrast, niosomes are safer but provide more superficial delivery (44). SLNs, with occlusive and hydrating effects, can sometimes deliver hydrophilic compounds more efficiently than niosomes (42).
4.3 Clinical Effectiveness
A clinical study on dapsone-loaded niosomes showed improvement in acne patients after 8 weeks, with minimal irritation, highlighting translational potential (45). Other reports confirm niosomes enhance antibacterial drug deposition in the skin while maintaining safety (46).
4.4 Limitations
While niosomes are cost-effective and stable, they often achieve less deep penetration compared with transfersomes or ethosomes. Optimization of surfactant type, cholesterol ratio, and vesicle size is critical to balance drug entrapment and penetration (41,42).
5. Challenges and Future Perspectives
Despite significant progress, the clinical translation of niosomal drug delivery systems in dermatology remains limited. Several challenges need to be addressed:
5.1 Scale-Up and Manufacturing
Most reported niosomal formulations are developed at laboratory scale. Transitioning to industrial-scale production poses challenges in terms of reproducibility, cost, and maintaining vesicle uniformity. Conventional methods such as thin-film hydration and sonication are not easily scalable (47,48). Advanced techniques like microfluidics offer better control but require specialized equipment and validation (49).
5.2 Stability Issues
Although niosomes are more stable than liposomes, instability can still arise from vesicle aggregation, fusion, leakage of encapsulated drug, or hydrolysis of surfactants. Long-term storage stability, particularly for herbal actives like flavonoids, remains a concern (50,51). Lyophilization and use of stabilizers may improve shelf-life but add complexity and cost (52).
5.3 Safety and Skin Irritation
While generally biocompatible, some surfactants may induce irritation or allergic reactions upon prolonged topical application. High concentrations of cholesterol or charge-inducing agents may alter skin tolerance (53). Systematic toxicological and dermatological safety studies are still scarce (54).
5.4 Regulatory and Translational Barriers
Regulatory approval of nanocarrier-based dermatological formulations is complex. Issues such as classification (cosmetic vs therapeutic), lack of standardized testing protocols, and absence of harmonized guidelines hinder market entry (55). Moreover, few clinical trials have been conducted, limiting clinical evidence (56).
5.5 Patient-Centric Considerations
Formulation must not only be effective but also cosmetically acceptable. Patient adherence depends on non-greasy textures, absence of odor, ease of application, and reduced dosing frequency (57). Integration of niosomes into film-forming gels and patches may help address compliance concerns (58).
5.6 Future Perspectives
Future research should focus on:
Overall, while niosomes show strong potential for advancing dermatological therapy, overcoming these scientific, regulatory, and translational hurdles will determine their successful clinical adoption.
CONCLUSION
Niosomes represent a versatile and effective drug delivery platform with significant potential in dermatological therapy. Their ability to enhance skin penetration, sustain drug release, protect labile compounds, and encapsulate a wide range of actives makes them particularly suitable for conditions such as acne, psoriasis, fungal infections, and inflammatory skin disorders. Compared with conventional formulations, niosomes offer improved therapeutic outcomes and better patient compliance, while also being more stable and cost-effective than many other vesicular systems. despite encouraging laboratory and preclinical results, translation into routine clinical use remains limited. Challenges related to large-scale manufacturing, stability during storage, regulatory approval, and comprehensive clinical validation must be addressed before widespread adoption can occur. Looking forward, integrating niosomes into advanced delivery systems such as film-forming gels, microneedle platforms, and hybrid nanocarriers offers exciting opportunities. With continued innovation, clinical research, and regulatory support, niosome-based formulations have the potential to transform dermatological therapy and bring safer, more effective, and patient-friendly treatments to market.
REFERENCES
Imran Rashid, Neha Srivastva, Niosomal Drug Delivery Systems: Emerging Trends in Dermatological Applications, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 8, 2569-2577, https://doi.org/10.5281/zenodo.21949716
10.5281/zenodo.21949716