Niosome: A Comprehensive Review of Development, Characterization and Applications

Lingesh Kumar MS¹, Oyitabu Ifunanya Mercy¹, Nayana DN¹, Shreya K¹, J Baseer UL Sumeer¹, Vemula Kusum Devi², Vijaya G Joshi³, CSR Lakshmi¹, Rama Bukka¹, Rama Nargund⁵, Shravan L Nargund¹, Shachindra L. Nargund⁴, Malviya Nidhi¹

¹Department of Pharmaceutics, Nargund College of Pharmacy, Bangalore - 85, Karnataka, India.

²Department of Pharmaceutics, NITTE College of Pharmaceutical Sciences, Bangalore – 64, India.

³Department of Pharmaceutics, Government College of Pharmacy, Bangalore - 27, Karnataka, India.

⁴Department of Pharmachemistry, Nargund College of Pharmacy, Bangalore - 85, Karnataka, India.

⁵Department of Pharmacology, Nargund College of Pharmacy, Bangalore - 85, Karnataka, India.

*Corresponding Author E-mail: nidhi.malviya7@gmail.com

ABSTRACT:

Niosomes were introduced as an alternative to traditional colloidal drug carriers such as emulsions, liposomes, and polymer-based systems. Niosomes offer enhanced stability, biocompatibility, and controlled drug release while overcoming limitations of conventional carriers. Niosomes are vesicular drug carriers composed of non-ionic surfactants, providing targeted and sustained drug release. The article explores strategies to minimize adverse effects using optimized manufacturing methods like thin-film hydration, reverse phase evaporation, and microfluidization. Advanced analytical techniques like electron microscopy, dynamic light scattering, and nuclear magnetic resonance are employed to characterize niosomes. This study evaluates niosome production techniques, drug loading efficiency, encapsulation ability, and controlled release properties, with a particular focus on drug delivery mechanisms. Topical niosomal gels are developed to enhance drug permeation, stability, and therapeutic efficacy. While conventional gels suffer from poor skin permeability, potential allergic reactions, and limited plasma drug concentration, niosomes improve drug retention, prevent enzymatic degradation, and develop penetration of larger molecules. This study highlights the possibility of niosomes as a potential drug delivery system for topical and systemic applications

KEYWORDS: Fungal diseases, Niosomes, Preparation methods, Evaluation parameters, Antimicrobial study methods, Preclinical data.

INTRODUCTION:

Fungal infections are responsible for approximately 1.7 million deaths globally every year. In India, more than a million individuals suffer from severe mycotic diseases and mucosal candidiasis, significantly affecting their quality of life. Approximately 4.1% suffer from a serious fungal disease. Fungal infections are characterized by red rashes and repeatedly substantial itching. Fungi produce a wide range of spectra of human infections, ranging from superficial skin infections in the outer layers of skin, hair, and mucous membrane to systemic infections. The fungi kingdom comprises rusts, yeasts, mushrooms, and molds, which are commonly found on the skin, mouth, throat, stomach, colon, rectum, and vagina.¹

Figure 1: Niosome

Niosomes are multi-lamellar vesicles composed of non-ionic surfactants, designed through the hydration of systemic non-ionic surfactants, either with or without sterols like cholesterol or other lipids (fig.1). They can diminish toxicity while influencing pharmacokinetics and bioavailability. Niosomes applied topically can prolong the drug's retention in the stratum corneum and epidermis while plummeting its systemic absorption. The noisome drug delivery system transports drugs to a specific site in the body, where they are released in a controlled manner through its bilayer, causing the encapsulated medicine to leak continuously, increasing bioavailability, and achieving a therapeutic impact over an extended length of time.²

Several drugs like miconazole, terbinafine, clotrimazole, fluconazole, ketoconazole, itraconazole, and griseofulvin are used in the treatment of fungal infections. These drugs exhibit a half-life fluctuating between 2 to 4 hours for lower doses and 4 to 8 hours for higher doses. The typical dosage is usually 200mg to 400mg daily once, with a dose frequency ranging from once or twice per week. Physicians have a wide range of therapy options, embracing liquid, solid, and semisolid dose formulations. Most diseases can be treated or cured by the usage of pharmaceutical dosage forms containing tablets, pills, capsules, creams, gels, ointments, liquids orals, and injectable drug carriers.³ Niosomes offers certain advantages over these dosage forms.

Advantages of Niosomes:

· A small volume of niosomal vesicles can efficiently enclose large amounts of materials.

· The vesicles can act as a depot to release the drug slowly and propose a controlled release.

· The properties of niosomes, comprising shape, fluidity, and size, can be readily adjusted by modifying their structural composition and production method.

· The quantity of drug used is very low for achieving its desired effect.

· The drug is protected from first-pass metabolism and gastrointestinal degradation.

· They increase the stability of the entrapped drug.

· Surfactants can be handled and stored without the need for special conditions.

· They will boost the oral absorption of drugs.

· Expand drug penetration through the skin.

· Niosomal dispersions in a water-based phase can be emulsified within a non-aqueous phase to control drug release and ensure the delivery of uniform vesicles.

Disadvantages of Niosomes:

· Time consuming process

· Specialized equipment is required for preparing

· Physical instability

· Agglomeration

· Merging of niosomes particles

· Dripping of entrapped drug

· The hydrolysis of encapsulated drugs restricts the dispersion's shelf life⁴

Method of Niosomes preparation:

Thin-Film hydration method, Micro fluidization method, Sonication method, Bubble method, Heating method, Reverse phase evaporation method, Supercritical Fluid method, Microemulsion method, Freeze-Thaw method, Multiple Membrane Extrusion method, Ether Injection method. Table 1 illustrates antifungal drugs and excipients used.

Table 1. Anti fungal drugs and excipients used

Drug	Therapeutic uses	Excipients
Ketaconazole	Infections like ringworm, jock itch, and athlete's foot, which frequently affect the groin and feet and can result in red, scaly rashes, can be treated with ketoconazole, an antifungal cream or lotion administered topically.	Lipid: cholesterol, Surfactant: span 40, span 60,Tween 60, Solvent: Methanol, chloroform, Gelling agent: carbapol 935, Hydroxypropyl methylcellulose(HPMC).^5
Fluconazole	By getting rid of the fungus or yeast that is causing the infection, fluconazole is a drug that cures and prevents fungal infections, including those brought on by Candida.	Lipid: cholesterol, Surfactant: pluronic F127, Span 60, Span 80, Tween 20, Solvent: ethanol, propylene glycol, Gelling agent:Carbopol 934, Hydroxypropyl methylcellulose,.^6
Eberconazole	A topical antifungal drug called eberconazole is used to treat skin infections that result in red, scaly rashes, such as ringworm, jock itch, and athlete's foot. Additionally, it works well against Malassezia furfur infections, which cause patches of discolored skin.	Lipid: cholesterol, Surfactant: Span 20, Triton-X, Solvent: Ethanol, Chloroform.^7
Clotrimazole	It is used for variety of fungal infections.	Lipids: Cholesterol, Surfactant: Sorbitan monoesters, Solvent: Ethanol, Dicetylphosphate, Methanol, Phospholipids, Gelling agent: Carbapol 934, Hydroxylpropyl methylcellulose.^8
Econazole	Athlete's foot, jock itch, ringworm, sun fungus, and cutaneous candidiasis are among the fungal and yeast skin infections that can be treated with the antifungal drug econazole.	Lipid: Cholesterol, Surfactant: Span 80, Solvent: Chloroform, Methanol.^9
Luliconazole	A topical antifungal with broad-spectrum action, improved skin penetration, and once-daily application, liconazole is used to treat tinea infections, candidiasis, and pityriasis versicolor.	Lipid: Cholesterol, Surfactant: Span 40, span 60, Tween 60, Solvent: Methanol, Gelling agent: Carbapol 934, Disodium hydrogen, orthophosphate, potassium dihydrogen orthophosphate.^10

Thin-film hydration method:

One popular approach for formulating niosomes is the thin-film hydration process. This technique involves liquifying cholesterol and surfactant in an organic solvent inside a rotary evaporator flask. Disappearance is subsequently utilized to dissolve the solvent, leaving a thin layer on the bottom of the flask. Multilamellar vesicles are created by adding an aqueous medium, like water or buffer, at a temperature higher than the surfactant's transition temperature while gently stirring the mixture. Unilamellar vesicles can be produced by sonicating these vesicles. Drugs are introduced based on how soluble they are in the aqueous or organic phase, and sonication aids in achieving a consistent distribution of niosome sizes.¹¹

Ether injection method:

Using a 14-gauge needle, niosomal components dissolved in ether are slowly injected into an aqueous phase at 60°C at a rate of 0.25ml/min using the ether injection method. Larger unilamellar vesicles with a bilayer structure are encouraged to form by the solvent gradient that is produced as ether vaporizes gradually. Both hydrophilic and lipophilic medications are successfully encapsulated using this technique. The existence of residual ether in the vesicle suspension, which is challenging to eliminate, is a significant drawback. Notwithstanding this limitation, the method is still useful for regulated niosome synthesis in drug delivery applications.¹²

Reverse phase evaporation method:

To perform the reverse phase evaporation process, dissolve cholesterol and surfactant in ether and chloroform, then add an aqueous drug solution. The mixture is then sonicated at 4–5°C to create a transparent gel. Additional sonication takes place following the addition of phosphate buffered saline (PBS). A thick niosome suspension is obtained by evaporating the organic component at 40°C with decreased pressure. To create niosomes, this suspension is diluted with PBS and heated for ten minutes at 60°C. This technique increases the effectiveness of drug encapsulation, although it requires several processing stages and organic solvents.¹³

Micro Fluidization method:

PEGylated and Triphenyltin (TPT) loaded niosomes were formulated through microfluidic mixing utilizing a NanoAssemblr™ system via nanoprecipitation. Span 60, 1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly(ethylene glycol), (2000) maleimide (9.9:9.9:0.2 molar ratio) and cholesterol were liquified in chloroform as the lipid phase, while TPT was in an acidic aqueous solution. Both phases were injected into separate inlets of a microfluidic micromixer at 65°C. Flow rate ratios (lipid to aqueous) of 1:1, 1:2, 1:3, and 1:5 were tested at a total stream rate of 12 mL/min. The final diffusions were collected and dialyzed against water for 4 hours.¹⁴

Sonication method:

The sonication method is a green, simple, and cost-effective technique for niosome preparation without organic solvents. In this process, the aqueous phase, medication and a mixture of surfactant and cholesterol is sonicated at 60°C using a titanium probe sonicator. The niosomes are then collected through freeze-drying, resulting in the formation of ultra-small vesiclesmaking it unsuitable for water-insoluble drugs. While it primarily yields slight unilamellar vesicles, it may also generate multilamellar vesicles. Its main advantages include minimal solvent use, ease of preparation, and uniform vesicle size, making it ideal for applications requiring nanosized niosomes.¹⁵

Bubble method:

An innovative one-step technique for creating niosomes and liposomes without the need for organic solvents is the bubble method. Temperature is controlled via a round-bottomed flask with three necks in a water bath. The third neck introduces nitrogen gas, while the other two include a reflux condenser and thermometer. Using a high-shear homogenizer, cholesterol and surfactant are dissolved in a buffer with pH 7.4 at 70°C, stirred for 15 seconds, and then bubbled with nitrogen gas at 70°C to create vesicles.¹⁶

Characterization of Niosomes:

Particle size, zeta potential, bilayer stiffness, surfactant composition, circulation time, stability, drug release, and surface shape are characteristics that identify niosomes. These features affect the therapeutic efficacy, bioavailability, and drug encapsulation. Niosomal formulations are optimized using sophisticated methods including dynamic light scattering, electron microscopy, and Differential scanning calorimetry to provide regulated and precise drug delivery.

Particle size:

Using Zetasizer, Dynamic light scattering (DLS), cumulant analysis was used to estimate the niosomes particle size (nm) and polydispersity index.¹⁷

Zeta potential (ZP):

Surface ZP of niosomes, measured using Zetasizer and DLS, plays a crucial role in stability. Negatively charged niosomes (−41.7 to −58.4mV) exhibit enhanced electrostatic stabilization, preventing aggregation effectively.¹⁸

Entrapment efficiency:

Entrapment efficiency of niosomes was determined by exhaustive dialysis, where un-entrapped drug diffused into PBS (pH 7.4, 10% methanol) until absorbance stabilized. Cholesterol enlarged vesicle size, entrapment efficiency, and stability by reducing permeability. Higher Cholesterol  content decreased drug release, enhancing bilayer rigidity, while charge increased entrapment by expanding interlamellar spacing.¹⁹

Bilayer characterization:

Bilayer characterization of niosomes influences drug entrapment. Atomic force microscopy, Nuclear magnetic resonance, and small angle X-ray scattering assess lamellae in multilamellar vesicles. Membrane rigidity is measured using fluorescence probes like 1,6-Diphenyl-1,3,5-hexatriene, which regulates micro viscosity via polarization. Higher fluorescence polarization indicates greater rigidity. Bilayer thickness is analyzed using Energy dispersive X-ray diffraction and fluorescence methods.²⁰

Stability:

Niosome stability is assessed by monitoring vesicle size, size distribution, and entrapment efficiency over months at different temperatures. Regular sampling evaluates drug retention using Ultraviolet spectroscopy(UV) or High performance liquid chromatography, ensuring sustained encapsulation and solidity during storage.²¹

Transmission electron microscope (TEM):

This is an electron cannon that uses condenser lenses and heated tungsten filament to generate electrons. TEM works similarly to a light microscope, using light rays to view images and electron beams to produce images.²²

In vitro drug release studies for niosomes:

Dialysis tubing is used to study in vitro drug release. Drug-loaded niosomal suspension is placed in a pre-soaked dialysis bag and immersed in buffer at 25°C or 37°C with constant shaking. Samples are taken at intervals, replaced with fresh buffer, and analyzed for drug content using an appropriate assay method.²³

Fourier transform infrared spectroscopy study:

The infrared spectrum of ketoconazole, excipients, and formulation was analyzed using the potassium bromide method. Drug release was studied at 37±0.5°C with stirring. Samples (5mL) were withdrawn periodically, replaced with fresh medium, and analyzed by UV spectrophotometry at 225nm. Tests were performed in triplicate.²⁴

Table 2. Evaluation parameter of Niosomal loaded gel

Evaluation of Niosomal loaded gel	Equipment
Visual Appearance	The prepared formulations were confirmed by its physico-rheological properties like colour, odour, texture and feel upon application
Measurement of Ph	Digital pH meter
Viscosity determination	Brookfield viscometer
Drug content studies	UV-spectrophotometer or chromatographic methods
Skin irritation test	Male wistar rats
In vitro antifungal activity	Cup plate techniques

Preparation of gel:

Various polymers, such as carbopol 934 and 940, Hydroxypropyl methylcellulose, etc., were used in varying ratios as the gelling agent during the preparation of the gel. The agents were combined while being stirred continuously to create a gel of the right consistency. The conventional gel was prepared by dispersing the drug into the gel matrix.²⁵ Table 2 presents the evaluation parameter of niosomal loaded gel.

In vitro drug release for niosomal gel:

The release of ketoconazole from niosomes was evaluated through membrane diffusion. Niosomes were dialyzed in PBS (pH 7.4, 10% methanol) at 37±0.5°C under continuous stirring. At regular intervals, 5 mL samples were collected, replaced with fresh medium, and analyzed using UV spectrophotometry at 225nm. All tests were conducted in triplicate.²⁶

Stability studies of gel:

The studies are carried out at different temperatures and according to ICH guidelines.²⁷

Ex vivo permeation studies:

Franz diffusion cell method is employed to determine the permeability/ flux/ drug release from the prepared niosomes. Phosphate buffers are placed in the receiver compartment. Donor compartment contains the prepared niosomal suspension or gel or patch. Samples withdrawn at regular time intervals are analyzed by either spectrophotometric or chromatographic techniques. Various biological membranes can be placed between the two compartments. Skin of pig ear²⁸ for ketoconazole, wister albino rats²⁹ for linezolid, and goat/ mice/ pig for cisplatin-loaded niosomal formulations has been reported.

Antifungal activity:

Agar-well diffusion method:

Using the agar diffusion (cup plate) method, the antifungal efficacy of ketoconazole niosomal gel was assessed in contrast to Aspergillus niger. The test microorganism was inoculated into Sabouraud's dextrose agar plates, and wells (5mm) were filled with 0.5ml of niosomal gel (‘F’) and marketed gel (‘M’). The plates were raised at 37°C for 24hours, and zones of inhibition were measured to compare antifungal activity.²⁸

Antifungal activity‐broth dilution method:

The agar diffusion method was used to investigate the antifungal activity of plain Farnesol and Farnesol-loaded niosomal gel against Candida albicans (ATCC 18804). C. albicans (1×10³ CFU/mL) was cultivated on Sabouraud dextrose agar, and wells (5 mm) were filled with plain Farnesol and Farnesol-loaded niosomal gel (2.5% w/w). A digital caliper was used to measure the inhibition zones following a 24-hour incubation period at 35°C.³⁰

Paper disk diffusion method:

The diffusion plate method was used to evaluate the antifungal efficacy of ketoconazole and griseofulvin niosomal gels against Aspergillus niger and Candida albicans. The inhibition zones surrounding to each disk were assessed after a 24-hour incubation period in order to assess and contrast the antifungal efficacy of the two formulations.³¹

Preclinical studies:

Naked and PEG niosomes of non-ionic surfactants (Brij 72, Span 20 and Tween 60) were evaluated in rats for their in-vivo pharmacokinetics hepatic disposition by liver perfusion experiments. Serum proteins results established that niosomes would display discrete in-vivo disposition characteristics dependent on the physicochemical properties of surfactants and could improve their in-vivo behavior.³² A study on curcumin-loaded niosomes on “KB” oral cancer cells, Human umbilical vein endothelial cells, and rats significantly prevented severe dysplasia compared to other treatments, suggesting their potential as a therapeutic option for oral cancer prevention.³³ A novel niosome preparation containing polyglyceryl-3-diisostearate, myristyl alcohol, and polysorbate-80 encapsulated zidovudine also known as azidothymidine (AZT) was studied for pharmacokinetic in rabbits showed prolonged AZT serum levels, slower clearance, and increased Area under curve and Mean retention time. Tissue distribution in rats confirmed higher AZT concentration and avoidance of reticuloendothelial uptake.³⁴ Researchers prepared pH-responsive niosomal methotrexate modified with ergosterol for possible anticancer activity and found significant increase in serum Blood urea nitrogen, serum creatinine, and serum lipid peroxidation in rats.³⁵

Table 3. Patents related to Niosomes

Title	Patent No	Description
Niosome-hydrogel drug delivery system^36	US20100068264A1	Non-ionic surfactant based niosome embedded in biodegradable, temperature, and pH sensitive cross linked chitosan hydrogel network modelled using a fluorescent dye for therapeutic drugs for cancer. Release rate controlled for more than three months.
Niosome-hydrogel drug delivery^37	WO2007123993A2	Niosomes for treating malignant cancer cells such as those found in the brain.
Method for fractionation of niosomes^38	RU-2754849-C1	Niosome preparation surfactants and hydration with phosphate buffer.
Ferrostatin-1 loaded niosomes and process therof^39	US 2006/0292211 A1	Thin-film hydration method.

Patents:

Table 3 shows patents related to niosomes and a brief description related to niosomes

CONCLUSION:

Niosomes are potential drug delivery devices due to their biodegradability, biocompatibility, simplicity of scaling, and controlled release patterns. They can be administered parenterally, topically, orally, pulmonary, ophthalmically, or cerebrally, among other ways. Niosomes can target epidermal side effects, increase therapeutic effectiveness, minimize systemic absorption, and improve skin penetration. They hold active materials that are significant to pharmaceuticals, such as proteins, genes, and tiny molecules, and are appropriate carriers for hydrophilic or lipophilic substances. Niosomes are a viable choice for topical formulations since they are as easy to prepare as other traditional drug carriers.

ACKNOWLEDGEMENT:

I would like to acknowledge and thank my guide Dr. Nidhi Malviya for her encouragement and guidance throughout the course of my review work and special thanks to Dr. Sachindra L Nargund, Nargund collage of pharmacy.

AUTHORS CONTRIBUTIONS:

All authors contributed equally to this work.

CONFLICT OF INTEREST STATEMENT:

The authors report no conflicts of interest in this work.

ABBREVIATIONS:

UV: Ulta violet; TEM: Transmission electron microscopy; AZT: Azidothymidine; DLS: Dynamic light scattering; TPT: Triphenyltin; PBS: Phosphate buffer saline; ZP: Zeta potential.

REFERENCES:

1.      B. Niyaz Basha. Formulation and evaluation of Gel containing Fluconazole-Antifungal Agent. Int J Drug Dev & Res.  3(4):109–128.

2.   Zaid Alkilani A, Hamed R, Abdo H, et al. Formulation and Evaluation of Azithromycin-Loaded Niosomal Gel: Optimization, In Vitro Studies, Rheological Characterization, and Cytotoxicity Study. ACS Omega. 2022; 7(44): 39782–39793; doi: 10.1021/acsomega.2c03762.

3.   Khanderao Rajaram Jadhav. Formulation and Evaluation of Nanosponge Based Topical Gel Preparation of Fluconazole. IJPPR. 19(3):597-616.

4.   Ag Seleci D, Maurer V, Stahl F, et al. Rapid Microfluidic Preparation of Niosomes for Targeted Drug Delivery. IJMS. 2019; 20(19): 4696   doi: 10.3390/ijms20194696.

5.   Shirsand S, Kanani K, Keerthy D, et al. Formulation and evaluation of Ketoconazole niosomal gel drug delivery system. Int J Pharma Investig. 2012; 2(4): 201 doi: 10.4103/2230-973X.107002.

6.   Sravan G, Latha K, Padmavathi R, et al. Formulation and Evaluation of Topical Gel Loaded with Fluconazole Niosomes. JPRI. 2022; 42–61   doi: 10.9734/jpri/2022/v34i34A36147.

7.   Aparajay P, Dev A. Development and Evaluation of Eberconazole-Loaded Niosomes. In: ECSOC-25 MDPI. 2021; 28; doi: 10.3390/ecsoc-25-11664.

8.   Shirsand SB, Kumar GR, Keshavshetti GG, et al. Formulation and Evaluation of Clotrimazole Niosomal Gel for Topical Application. RGUHS J Pharm Sci. 2015; 5(1): 32–38; doi: 10.5530/rjps.2015.1.4.

9.   Bayan MF, Chandrasekaran B, Alyami MH. Development and Characterization of Econazole Topical Gel. Gels. 2023; 9(12): 929; doi: 10.3390/gels9120929.

10. Mishra S, Gupta RA. Formulation and Evaluation of Niosomal Gel of Antifungal Luliconazole. J Drug Delivery Ther. 2022; 12(6-S):47–54; doi: 10.22270/jddt.v12i6-S.5705.

11. Thabet Y, Elsabahy M, Eissa NG. Methods for preparation of niosomes: A focus on thin-film hydration method. Methods. 2022; 199: 9–15; doi: 10.1016/j.ymeth.2021.05.004.

12. Palak P, Rani R, Kumar R, et al. Formulation and Evaluation of Niosomal gel using Tretinoin and Clindamycin combination. J Drug Delivery Ther. 2024; 14(3): 106–114; doi: 10.22270/jddt.v14i3.6477.

13. Abdel Salam L, Abdelmottaleb M, Geneidi A. Formulation and Characterization of Proniosomal Gels loaded with Levofloxacin for dermal drug Delivery. Archives of Pharmaceutical Sciences Ain Shams University. 2021; 5(2): 288–303; doi: 10.21608/aps.2021.109363.1077.

14. Aldawsari MF, Khafagy E-S, Moglad EH, et al. Formulation optimization, in vitro and in vivo evaluation of niosomal nanocarriers for enhanced topical delivery of cetirizine. Saudi Pharmaceutical Journal. 2023; 31(9): 101734; doi: 10.1016/j.jsps.2023.101734.

15. Patel KK, Kumar P, Thakkar HP. Formulation of Niosomal gel for Enhanced Transdermal Lopinavir Delivery and Its Comparative Evaluation with Ethosomal Gel. AAPS PharmSciTech. 2012; 13(4): 1502–1510; doi: 10.1208/s12249-012-9871-7.

16. Mawazi SM, Ge Y, Widodo RT. Niosome Preparation Techniques and Structure—An Illustrated Review. Pharmaceutics. 2025; 17(1): 67; doi: 10.3390/pharmaceutics17010067.

17. Garg AK, Maddiboyina B, Alqarni MHS, et al. Solubility enhancement, formulation development and antifungal activity of luliconazole niosomal gel-based system. Journal of Biomaterials Science, Polymer. 2021; 32(8): 1009–1023; doi: 10.1080/09205063.2021.1892471.

18. Ning M, Guo Y, Pan H, et al. Preparation, in Vitro and in Vivo Evaluation of Liposomal/ Niosomal Gel Delivery Systems for Clotrimazole. Drug Development and Industrial Pharmacy. 2005; 31(4–5): 375–383;  doi: 10.1081/DDC-54315.

19. Saeidi Z, Giti R, Emami A, et al. Thermosensitive and mucoadhesive gels containing solid lipid nanoparticles loaded with fluconazole and niosomes loaded with clindamycin for the treatment of periodontal diseases: a laboratory experiment. BMC Oral Health. 2024; 24(1): 551; doi: 10.1186/s12903-024-04322-6.

20. Karim K, Mandal A, Biswas N, et al. Niosome: A future of targeted drug delivery systems. J Adv Pharm Technol Res. 2010; 1(4): 374; doi: 10.4103/0110-5558.76435.

21. Durak S, Esmaeili Rad M, Alp Yetisgin A, et al. Niosomal Drug Delivery Systems for Ocular Disease—Recent Advances and Future Prospects. Nanomaterials. 2020; 10(6): 1191; doi: 10.3390/nano10061191.

22. Morteza-Semnani K, Saeedi M, Akbari J, et al. Green formulation, characterization, antifungal and biological safety evaluation of terbinafine HCl niosomes and niosomal gels manufactured by eco-friendly green method. Journal of Biomaterials Science, Polymer. 2022; 33(18): 2325–2352; doi: 10.1080/09205063.2022.2103626.

23. Uthaiwat P, Priprem A, Puthongking P, et al. Characteristic Evaluation of Gel Formulation Containing Niosomes of Melatonin or Its Derivative and Mucoadhesive Properties Using ATR-FTIR Spectroscopy. Polymers. 2021; 13(7): 1142; doi: 10.3390/polym13071142.

24. Soliman OAE-A, Mohamed EA, Khatera NAA. Enhanced ocular bioavailability of fluconazole from niosomal gels and microemulsions: formulation, optimization, and in vitro–in vivo evaluation. Pharmaceutical Development and Technology. 2019; 24(1): 48–62;  doi: 10.1080/10837450.2017.1413658.

25. Sharma R. Formulation and Evaluation of Clindamycin phosphate Niosomes by using reverse phase evaporation Method. JDDT. 2019; 9(3-S):515–523;  doi: 10.22270/jddt.v9i3-s.2895.

26. Teaima MH, El Mohamady AM, El-Nabarawi MA, et al. Formulation and evaluation of niosomal vesicles containing ondansetron HCL for trans-mucosal nasal drug delivery. Drug Development and Industrial Pharmacy. 2020; 46(5): 751–761; doi: 10.1080/03639045.2020.1753061.

27. Sukanya Patil, Jaya Agnihotri. Formulation development, optimization, and characterization of anti-fungal topical biopolymeric film using a niosomal approach. Int J Sci Res Arch. 2023; 8(1): 194–209; doi: 10.30574/ijsra.2023.8.1.0031.

28. Shirsand S, Kanani K, Keerthy D, et al. Formulation and evaluation of Ketoconazole niosomal gel drug delivery system. Int J Pharma Investig. 2012; 2(4): 201; doi: 10.4103/2230-973X.107002.

29. Inayathulla, Goudanavar P, Acharya A. Development and Evaluation of In-situ gel containing Linezolid and Diclofenac Sodium in the treatment of Periodontitis. Asian Jour Pharm and Technol.  2020; 10(1): 20; doi: 10.5958/2231-5713.2020.00005.7.

30. Barot T, Rawtani D, Kulkarni P. Development, characterization and in vitro–in vivo evaluation of Farnesol loaded niosomal gel for applications in oral candidiasis treatment. Heliyon. 2021; 7(9): e07968; doi: 10.1016/j.heliyon.2021.e07968.

31. Jadon PS, Gajbhiye V, Jadon RS, et al. Enhanced Oral Bioavailability of Griseofulvin via Niosomes. AAPS PharmSciTech. 2009; 10(4):1186; doi: 10.1208/s12249-009-9325-z.

32. Shehata T, Kimura T, Higaki K, et al. In-vivo disposition characteristics of PEG niosome and its interaction with serum proteins. International Journal of Pharmaceutics. 2016; 512(1): 322–328; doi: 10.1016/j.ijpharm.2016.08.058.

33. Fazli B, Irani S, Bardania H, et al. Prophylactic effect of topical (slow-release) and systemic curcumin nano-niosome antioxidant on oral cancer in rat. BMC Complement Med Ther. 2022; 22(1): 109; doi: 10.1186/s12906-022-03590-5.

34. Gopinath D, Ravi D, Karwa R, et al. Pharmacokinetics of zidovudine following intravenous bolus administration of a novel niosome preparation devoid of cholesterol. Arzneimittelforschung. 2001; 51(11): 924–930; doi: 10.1055/s-0031-1300139.

35. Barani M, Reza Hajinezhad M, Sargazi S, et al. Simulation, In Vitro, and In Vivo Cytotoxicity Assessments of Methotrexate-Loaded pH-Responsive Nanocarriers. Polymers (Basel). 2021; 13(18): 3153; doi: 10.3390/polym13183153.

36. Norma Alcantar Eva C. Williams Ryan Toomey. Niosome-Hydrogel Drug Delivery System. 2009.

37. Norma Alcantar Kristina Dearborn Michael Vanauker Ryan Toomey Elizabeth Hood. Niosome-Hydrogel Drug Delivery. 2008.

38. Kovalev Dmitrij Anatolevich Zhirov Andrej Mikhajlovich Pisarenko Sergej Vladimirovich Kulichenko Aleksandr Nikolaevich Shakhova Valeriya Nikolaevna. Method for Fractionation of Niosomes. 2021.

39. Shivani Gurjar, Farhan Mazahir, Awesh Kumar Yadav, Nidhi Srivastava, Ankita Sharma. Ferrostatin-1 Loaded Niosomes and Process Therof. 2023.

Received on 21.04.2025      Revised on 12.08.2025

Accepted on 23.10.2025   Published on 20.01.2026

Available online from January 27, 2026

Asian J. Pharm. Tech. 2026; 16(1):45-51.

DOI: 10.52711/2231-5713.2026.00008

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