A Review on Niosome in Ocular Drug Delivery System and Their Current Approaches

 

Dimpal R. Sarkar*, Neha D. Naringe, Pankaj Dhapke, Nitin Padole, Nilakshi Dhoble,
Jagdish R. Baheti

Kamla Nehru College of Pharmacy, Butibori, RTMNU University, Nagpur, Maharashtra, India – 441108.

*Corresponding Author E-mail: dimpalsarkar143@gmail.com

 

ABSTRACT:

The eye is a complicated organ with a number of defense mechanisms and barriers. The provision of vital medications via the proper delivery channels and vehicles is crucial because this organ is susceptible to a variety of infections, hereditary abnormalities, and visual impairments. Due to low medication absorption, the most popular method of administration—topical—may not be as effective as it may be. Nanocarrier-based medication delivery systems of the latest generation are safe, efficient, and targeted, and they can get beyond restrictions brought on by the intricate structure of the eye. Nanotechnology actively participates in ophthalmology and ocular medication delivery systems through a variety of nanoparticles, including niosomes, liposomes, micelles, dendrimers, and other polymeric vesicles. Because of their affordability and storage durability, niosomes—non-ionic surfactant vesicles—are becoming popular nanocarriers in drug delivery applications. A hydrating mixture of cholesterol and non-ionic surfactants self-assembles to produce niosomes. As a result, another name for them is non-ionic surfactant vesicles (NSVs). Niosomes are non-toxic, non-immunogenic, non-carcinogenic, and biodegradable. The niosome, its nature, preparation techniques, and niosome-based therapeutic approaches for ocular diseases are all covered in this review. problems with ocular drug administration, methods for enhancing ocular bioavailability, uses, benefits and drawbacks, latest research, and hopes for niosomal drug delivery systems in the future.

 

KEYWORDS: Niosome, non-ionic surfactant vesicle, Nanocarriers, Method of Preparation, disease challenges, current approaches.

 

 


INTRODUCTION:

The eye is our soul's window. To shield this sensory organ from its environment, the human eye has a number of defenses and barriers. Treating ocular illnesses and delivering medications to various eye compartments are extremely difficult because of this unique structure.

 

 

The most common kind of ocular treatment for the anterior region of the eye, which comprises the conjunctiva, cornea, sclera, and anterior uvea, is topical eye drops1. This drug delivery method does have several drawbacks, though. The sorption time for medications while using eye drops is roughly two to three minutes. As a result, administered drops are rapidly removed from the eye's surface. Age-related macular degeneration and diabetic macular edema are examples of posterior segment ocular diseases. The most frequent causes of blindness and visual impairment are CMV infection, glaucoma, and proliferative vitreoretinopathy. In certain instances, genetic disorders may also be the cause of retinal degeneration and the ensuing blindness2. Intravitreal injections are presented as an alternate method of drug administration because topical ocular medications encounter difficulties reaching the posterior regions. However, because the injection is intrusive, new drug delivery systems must be developed in order to maintain the medication concentration for longer periods of time and reduce the number of doses3. In ophthalmology, nanotechnology is useful because it offers specific carriers that provide new methods of transfer and release, increasing the effectiveness of medications, and facilitating intracellular delivery4,5.

 

Anatomy of Eye and its Barrier:

The most amazing sensory organ is the eye. It is shielded by blinking, tears, eyelids, and eyelashes. Tears remove the irritating substances and stop bacterial infections. Three concentric substrates make up the eye: the fibrous tunic on the outside, the vascular tunic on the inside, and the middle covering. The cornea and sclera are in the outermost portion. The iris, ciliary body, and choroid are all part of the mid-covering known as the uvea (figure 1)6.

 

 

Figure 1. Human eye anatomy, and the drug administration routes.

(1) The cornea as a main route of drug delivery to the anterior section.

(2) The retinal capillary endothelium and Retinal pigment epithelium as the main barriers for systemically administered drugs.

(3) An invasive strategy to gain the vitreous called intravitreal injection.

 

I. FIBROUS TUNIC:

The anterior portion of the eye, the pupil, and the foreside of the iris are all covered by the dome-shaped cornea. From front to back, the cornea is made up of five layers: the epithelium, stroma, Bowman's membrane, and Descemet's the endothelium and membrane. The "white of the eye" is the sclera. It is a thick layer of connective tissue composed of fibroblasts and collagen fibers.

 

II. VASCULAR TUNIC:

The colored part of the eye that is visible is called the iris. Pigment granules found in the iris epithelium absorb light and lipophilic medications. Aqueous humor generation is the primary function of the ciliary body. It is the main source of drug-metabolizing enzymes in the eyes, which are in charge of detoxifying and eliminating drugs from the eyes.

The choroid, which is abundant in blood vessels, lines the back five-sixths of the sclera's inner surface.

 

III. RETINA:

The inside component of the eye is called the retina. The retina uses choroid blood vessels and retinal vessels for oxygenation. When the retina detects light, it converts it into signals, which are then sent to the brain via the optic nerve. The anterior and posterior segments make up the two halves of the human eye. The iris, cornea, aqueous fluid, and lens make up the anterior region of the eye, which makes up one sixth of the whole eye. The posterior region of the eye, which comprises the retina, vitreous body, back of the sclera, and choroid, makes up the remaining five-sixth of the eye7.            

 

The ocular compartment contains numerous obstacles. The conjunctiva, sclera, and blood-retina barrier are some of the barriers that divide the eye from the rest of the body. These obstacles make it impossible to administer ocular medications topically and systemically. In ocular delivery, there are three main categories of obstacles. Precorneal, static, and dynamic barriers are the three types. The several layers of the cornea, sclera, and retina, including the blood-aqueous barrier, make up the static barrier8.

 

Niosomes as Novel Drug Transport Mechanisms:

Niosome structure:

As seen in Figure 2, it is a bilayered spherical structure made of cholesterol and non-ionic surfactant. The hydrophobic end of the non-ionic surfactant is oriented inward, toward the lipophilic phase, in this case. The closed lipid bi-layer that envelops solutes in the aqueous phase, on the other hand, is created when the hydrophilic end faces outward (toward the aqueous phase). This bi-layer resembles the outer and inner surfaces of the hydrophilic area, sandwiched between them by the lipophilic area 9,10. Based on the size of a vesicle, niosomes are divided into three types, as illustrated in Figure 3 and Table 1.

 

 

Figure 2: Schematic representation of structure of Niosome 11

 

 


Table 1: Types of Niosomes 12

Sr. No

Types

Size

1

Small unilamellar vesicle

0.025-0.05

2

Large unilamellar vesicle

≥ 0.05 µm

3

Multi lamellar vesicle

≥ 0.10 µm


 


Figure 3. Typical vesicle size of niosomes.

 


Classification:

Niosomes are divided into three groups according to their size and number of bilayers (shown in figure 3)13:

 

a)   Small Unilamellar Vesicles (SUV):

·       It can be made from multilamellar vesicles using the French press, extrusion, and sonication methods.

b) Large Unilamellar Vesicles (LUV):

·       Due to their high aqueous/lipid compartment ratio, large unilamellar vesicles (LUV) have the ability to entrap a greater volume of bioactive molecules.

c)   Multi Lamellar Vesicles (MLV):

·       The most often utilized niosomes are called Multi Lamellar Vesicles (MLV), which have several bilayers.

·       With a diameter ranging from 0.5 to 10 µm, MLVs are easy to produce and exhibit mechanical stability for an extended period of storage14.

 

Advantages of niosomes15:

i.      Niosomes are reasonably priced.

ii.    More stable than liposomes due to the presence of phospholipids, which are readily oxidized in liposomes.

iii.  They improve the stability of the entrapped medication and are osmotically stable and active.

iv.   They improve the medicines' skin penetration.

v.     Serve as a depot and release the medication in a regulated way.

vi.   Make medications that are poorly absorbed more bioavailable orally.

vii. The surfactants in niosomes can be handled without any particular conditions.

viii.It has the ability to capture hydrophilic and lipophilic 

       medications.

 

The advantages of niosomes compared to other nanoencapsulation technologies are16:

i.      Compared to phospholipids in liposomes, surfactants are more stable in niosomes.

ii.    Only a straightforward preparation process and large-scale manufacturing are needed.

iii.  The cost of producing niosomes is low because the equipment and excipients needed are inexpensive.

iv.   More stable than liposomes at normal temperature.

v.     Have an extended shelf life.

 

Disadvantages of niosomes:

i.      Treatment does not end immediately when sustained release medicine is administered.

ii.    The doctor's ability to modify the dosing schedule is limited.

iii.  Time-intensive.

iv.   Specialized machinery was needed for production.

v.     It causes the contained medication to release.

 

Composition of niosomes

·       The essential components are

I.      Cholesterol

II.    Non-ionic surfactants

III.  Other Additives

 

I. Cholesterol:

The most prevalent additions in niosomal systems are cholesterol and its derivatives. It is a waxy metabolite of steroids that is present in cell membranes. It creates the vesicles, increases stability, and lessens agglomeration when non-ionic surfactants are used. Additionally, it adds stiffness to niosome formation and orientational order to the niosomal bilayer17.

 

II. Non-ionic surfactants:

It has a hydrophobic tail and a hydrophilic head group. It is the primary element involved in the production of niosomes. The hydrophobic moiety is made up of one stearyl group, one fluro group, or two or three alkyl chains. When entrapped in water-soluble surfactants like Tween 20, Tween 80, etc., niosomes exhibit improved ocular bioavailability because the surfactants function as penetration enhancers, assisting in the removal of the mucus layer and the disruption of junctional complexes 18.

 

Commonly used surfactants include Tweens, which come in Tween 20, Tween 40, Tween 60, and Tween 80, as well as span, which comes in a variety of grades, including span 20, span 40, span 60, span 80, and span 85. Other surfactants that are utilized include polysorbates, ether-linked, di-alkyl-chain, ester-linked, and sorbitan esters19.

 

III. Other additives:

Charge inducers are primarily crucial to the formation of niosomes. It stops vesicles from flocculating, aggregating, and fusing while also raising the surface charge density. Diacetyl phosphate (DCP), which has a negative charge, and stearylamine (SA), which has a positive charge, are often employed charge inducers20.

 

METHOD FOR THE PREPARATION OF NIOSOMES:

The general approach primarily entails the evaporation of organic solvents, which forms a lipid film, and hydration, which produces niosomes. There are several approaches to the preparation:

 

A. FORMULATION OF LARGE UNILAMELLAR VESICLES:

1.ETHER INJECTION METHOD:

Lipids are injected or introduced gradually to create vesicles. This involves placing cholesterol and non-ionic surfactants in a beaker with warm water and keeping the temperature at 60ºC (figure 4). Here, the phosphate buffer is an aqueous solution. Using a 14-gauge needle, ether containing the drug solution is gradually added to the aqueous solution. The ether is then vaporized, resulting in the creation of single-layered niosome vesicles. The size range of niosomes is 50–1000nm. The primary drawback of this approach is the difficulty in eliminating the trace amount of ether present in the vesicle suspension21.


 

 

Figure-4: Ether injection method

 

 

 

Figure-5: Ethanol Injection Method.

 

 

Figure 6. Schematic representation of reverse-phase evaporation method.

 

 

Figure 7: Thin film hydration (hand shaking) method.

 


2. ETHANOL INJECTION METHOD:

This approach involves gently injecting the medication in ethanol, cholesterol, stearic acid, and surfactant into a heated aqueous phase using a needle (see figure 5). The ethanol solvent is then gradually evaporated, creating an ethanol gradient across the cholesterol and surfactant layer at the ethanol-water interface that leads to the production of vesicles 22.

 

3. REVERSE PHASE EVAPORATION (REV) METHOD:

This process uses evaporation to remove the volatile organic solvent. Add cholesterol and surfactant to the ether and chloroform mixture in an equal ratio, or 1:1. The drug-containing aqueous phase is added to the solution above, and the two phases that result are sonicated for a short while. After that, phosphate buffer saline is added, and sonication creates a transparent gel. Evaporation removes the organic phase at low pressure.

Niosomes are formed by heating the obtained solution on a water bath at the ideal temperature of 45ºC for 10 minutes after further diluting it with phosphate buffer saline 23.

 

B. FORMULATION OF MULTI LAMELLAR VESICLES:

4. THIN FILM HYDRATION METHOD (HAND SHAKING METHOD):

Non-ionic surfactant and membrane stabilizer lipid are combined with organic solvents such as diethyl ether, methanol, and chloroform in a round-bottom flask. A thin layer of solid mixture is then formed on the flask's circular bottom wall as a result of the volatile solvent's evaporation.

The film rehydrates when the solvent is added while being gently stirred. Multi-lamellar vesicles are created using this technique 24.

 

5. TRANS MEMBRANE PH GRADIENT PROCESS:

Lipid mixture was dissolved in the organic solvent, resulting in a lipid film on the flask's round bottom wall. When this is combined with strong agitation, an acid such as citric acid is added, which hydrates the films and creates multi-lamellar vesicles. These are subjected to sonication and the freeze-thaw cycle. After that, an agitated API aqueous solution was added. Disodium phosphate was used to elevate the pH of the mixture. Niosomes are then produced by heating the mixture to 65°C 24.

 

C.FORMULATION OF SMALL UNILAMELLAR VESICLES:

6. SONICATION METHOD:

It is a standard method for creating niosome vesicles. Using this approach, a 10-ml glass vial containing the medication, surfactant, and cholesterol is combined with buffer. The mixture was sonicated for approximately three minutes using a titanium probe, which produced noise 25.

 

7. MICRO FLUIDIZATION:

The jet principle was applied to the creation of niosmes. Vesicles are created when the lipid and aqueous phases contact quickly 25.


 

    

Figure 8: Schematic representation of the preparation of niosomes via transmembrane pH gradient Process.

Figure 9: Schematic representation of Sonication.

 

 

Figure 10: Schematic representation of Micro Fluidization.

 


8. MULTIPLE MEMBRANE EXTRUSION METHOD:

Di-acetyl phosphate, cholesterol, and a non-ionic surfactant were dissolved in chloroform and then evaporated. causes the aqueous phase to hydrate when a thin layer is formed. A suspension of niosomes is transported through a polycarbonate membrane 26.

 

 

Figure 11. Schematic representation of the preparation of niosomes via multiple membrane extrusion method.

 

 

 

 

9.BUBBLE METHOD:

This technique uses a round-bottom flask with three neck sections. One each for the nitrogen supply input, thermometer, and reflux. After being dissolved in phosphate buffer saline, the lipid mixture was put through a high pressure homogenizer. The vesicle is then produced by supplying nitrogen gas at 65–70°C, which causes bubbles to form26.

 

 

Figure 12: Schematic representation of Bubble method.

 

Niosome based treatment strategies in ocular diseases:

1.Glaucoma:

It is a neurological condition that needs lifelong care. It is classified as an optic neuropathy and is typified by the apoptotic death of retinal ganglion cells (RGCs), which causes nerve axon degeneration and abnormalities in the visual field. Different forms of glaucoma exist. The most significant factor influencing the prognosis of Primary Open Angle Glaucoma is elevated intraocular pressure (IOP) brought on by a buildup of aqueous humor in the anterior chamber as a result of either an obstruction in the drainage system or an excess of fluid production. Elevated IOP causes an imbalance in the blood flow to the retina, which results in optic nerve degeneration. The primary goal of treatment is to lower intraocular pressure using a variety of techniques, such as medication, laser therapy, and surgery.

 

The drug delivery systems used to treat glaucoma are called niosomes. Niosomes have numerous benefits in drug delivery, including reduced ocular toxicity, prolonged IOP-lowering action, increased corneal penetration, and less frequent administration27.

 

1.    Conjunctivitis:

The inflammation or infection of the conjunctiva, the transparent mucous membrane found in the sclera, is known as conjunctivitis. There are several varieties of conjunctivitis, including bacterial, viral, and allergic conjunctivitis, which can be either acute or chronic. Bacterial, viral, fungal, parasitic, and chlamydial conjunctivitis are all considered infectious conjunctivitis. Allergens, irritants, and toxins are the causes of non-infectious conjunctivitis. Antibiotics, antifungals (polyenes, azoles, imidazoles, triazoles, pyrimidines, and echinocandins), and antivirals (aciclovir, trifluridine, and valaciclovir) are the main treatments applied topically. For some time now, researchers have been looking into nanotechnological formulations to boost the effectiveness of these medications. Niosomes have been identified as the most effective ocular medication carriers, releasing the drug in a consistent and predictable fashion28.

 

3. Retinal diseases:

Retinal degeneration is the outcome of a variety of conditions known as inherited retinal diseases (IRD). IRD is caused by gene alterations that happened in the inner retinal layer. mutations expressed in the retinal pigment epithelium (RPE) or photoreceptor in the majority of instances. A new cationic niosome has been developed for use in retinal gene delivery, and research into retinal gene delivery using niosome carriers for non-viral vectors has been conducted29.

 

4. Keratitis:

It is one of the main causes of blindness in the globe and is caused by inflammation in the cornea brought on by infections with bacteria, fungi, and viruses. Similar eye symptoms, including redness, discomfort, blurred vision, and tearing, are displayed by patients. Numerous noisome formulations were created and assessed, and they show prolonged drug release30.

 

Future Prospects of niosomes:

One possible medication delivery mechanism is niosomes. Niosomes have been effectively employed as a medication carrier during the past thirty years to address biopharmaceutical issues such adverse effects, low chemical stability, and insolubility of medications. Toxic anticancer, anti-inflammatory, anti-infective, anti-AIDS, and antiviral medications, among others, can be encapsulated in niosomes to improve bioavailability and targeting qualities while lowering drug toxicity and adverse effects. Niosome handling and storage don't require any particular circumstances. Niosomal drug carriers are safer than ionic ones, which are more toxic and unstable.

 

Challenges in Ocular Drug Delivery:

§  Limited Drug Absorption: The corneal epithelium, conjunctiva, and sclera are among the protective layers of the ocular surface that restrict medication absorption.

§  Short Retention Time: The therapeutic impact of drugs given topically is diminished because tears quickly wash them away.

§  Low Bioavailability: Ocular obstacles may cause medications to have low bioavailability at the target site, even with controlled-release formulations.

Current approaches of ocular drug delivery system:

By delivering therapeutic agents straight to the eye, ocular drug delivery devices (ODDS) minimize systemic side effects while guaranteeing that the medication reaches the intended location. Because of its architecture and physiology, the eye poses special difficulties, such as the corneal epithelium, blood-aqueous barrier, blood-retinal barrier, and the short half-life of medication formulations. In order to improve drug delivery to the ocular tissues, a number of strategies are being developed, particularly for the treatment of conditions like glaucoma, diabetic retinopathy, age-related macular degeneration (AMD), uveitis, and ocular infections.

 

Approaches in ophthalmic drug delivery systems:

A number of approaches have been used in the early stages for better results. These approaches, categorized into two types, are:

·       Bioavailability improvement and

·       Controlled release drug delivery

 

Viscosity and penetration enhancers, prodrugs, gels, and liposomes are used in the first category to optimize corneal medication absorption and reduce precorneal drug loss. The second one uses a sustained delivery mechanism, such as implants, inserts, nanoparticles, microparticles, and colloids, to administer the active ophthalmic component in a regulated and continuous manner. Traditional methods that increase bioavailability include viscosity enhancers, gel, penetration enhancers, prodrugs, and liposomes. On the other hand, more recent innovations like ocuserts, nanosuspension, nanoparticles, liposomes, niosomes, and implants increase both bioavailability and controlled drug release in the anterior segment of the eye. In the back part of

 

Drugs enter the eye through periocular pathways, subconjunctival injections, iontophoresis, and intravitreal injections31,32.

 

Approaches to improve ocular bioavailability:

Use of viscosity enhancers:

Due to their ability to increase viscosity and, consequently, the drug's penetration into the anterior chamber of the eye by decreasing the rate of elimination from the preocular area, resulting in an increase in precorneal residence time and transcorneal penetration, viscosity-increasing polymers are highly preferred additives in ophthalmic formulations. However, their effects on improving bioavailability in humans are negligible. Polymers include methylcellulose, hydroxylethylcellulose, hydroxylpropyl methylcellulose (HPMC), hydroxypropyl cellulose, polyvinyl alcohol (PVA), and polyvinylpyrrolidone (PVP)33.

 

Gel formulation:

Gels exhibit stiffness in the steady-state and are known to be highly diluted cross-linked systems. Although gels are typically liquids, their three-dimensional cross-linked structure within the liquid causes them to behave like solids34.

 

Niosomes and discosomes:

Drugs that are hydrophobic or amphiphilic may be delivered using niosomes, which are non-ionic surfactant vesicles. Chemical instability, oxidative phospholipid breakdown, and the price and purity of natural phospholipids are the main drawbacks of liposomes. Because they can entrap both hydrophobic and hydrophilic medicines and are more chemically stable than liposomes, niosomes were created to circumvent this. They don't need specific handling methods and are non-toxic35. When compared to timolol maleate solution, Vyas and colleagues found that the ocular bioavailability of timolol maleate encapsulated in niosomes was approximately 2.49 times higher. Not ionic Timolol maleate-loaded discoidal vesicles, or "discomes," based on surface-active compounds were created and evaluated for their in vivo characteristics. According to in vivo research, if the medication was loaded using a pH gradient approach, the contents of the discomes were released in a biphasic profile35.

 

CONCLUSION:

Niosomes are a new and effective method of medication administration since they are non-ionic surfactant vesicles. The use of niosomes for ocular medication delivery has advanced significantly in recent years. Non-ionic surfactant and cholesterol can be used to encapsulate a variety of medications into niosomes. Niosomes have improved stability, lessen harmful effects, and allow continuous release of the chemical they contain. Niosomes don't require any particular handling or storage conditions, unlike other drug delivery systems like liposomes. In conclusion, niosomes are a very useful tool for medication delivery in the treatment of many different disorders.

 

REFERENCES:

1.      Urtti A. Challenges and obstacles of ocular pharmacokinetics and drug delivery. Advanced Drug Delivery Reviews. 2006 Nov 15; 58(11):1131-1135. DOI: 10.1016/j.addr.2006.07.027

2.      Lajunen, T.; Nurmi, R.; Kontturi, L.; Viitala, L.; Yliperttula, M.; Murtomaki, L.; Urtti, A. Light activated liposomes: Functionality and prospects in ocular drug delivery. J. Control. Release 2016, 244, 157–166. DOI: 10.1016/j.jconrel.2016.08.024

3.      Del Amo, E.M.; Urtti, A. Current and future ophthalmic drug delivery systems. A shift to the posterior segment. Drug Discov. Today 2008, 13, 135–143. DOI: 10.1016/j.drudis.2007.11.002

4.      Yetisgin, A.A.; Cetinel, S.; Zuvin, M.; Kosar, A.; Kutlu, O. Therapeutic Nanoparticles and Their Targeted Delivery Applications. Molecules 2020, 25, 2193. DOI: 10.3390/molecules25092193

5.      Sharaf, M.G.; Cetinel, S.; Heckler, L.; Damji, K.; Unsworth, L.; Montemagno, C. Nanotechnology-Based Approaches for Ophthalmology Applications: Therapeutic and Diagnostic Strategies. Asia Pac. J. Ophthalmol. (Phila) 2014, 3, 172–180. DOI: 10.1097/APO.0000000000000059

6.      Vaddavalli PK, Garg P, Sharma S, Sangwan VS, Rao GN, Thomas R. Role of confocal microscopy in the diagnosis of fungal and acanthamoeba keratitis. Ophthalmology. 2011 Jan 1; 118(1):29-35. DOI: 10.1016/j.ophtha.2010.05.018

7.      Kaur IP, Rana C, Singh H. Development of effective ocular preparations of antifungal agents. Journal of Ocular Pharmacology and Therapeutics. 2008 Oct 1; 24(5):481-94. DOI: 10.1089/jop.2008.0031

8.      Rodrigues GA, Lutz D, Shen J, Yuan X, Shen H, Cunningham J, Rivers HM. Topical drug delivery to the posterior segment of the eye: addressing the challenge of preclinical to clinical translation. Pharmaceutical Research. 2018 Dec; 35(12):245.DOI: 10.1007/s11095-018-2519-x

9.      Yeo PL, Lim CL, Chye SM, Ling AP, Koh RY. Niosomes: a review of their structure, properties, methods of preparation, and medical applications. Asian Biomedicine. 2017 Aug 1; 11(4):301-314. DOI: https://doi.org/10.1515/abm-2018-0002

10.   Amoabediny, G., Haghiralsadat, F., Naderinezhad, S., Helder, M. N., Akhoundi Kharanaghi, E., Mohammadnejad Arough, J., & Zandieh-Doulabi, B. Overview of preparation methods of polymeric and lipid-based (niosome, solid lipid, liposome) nanoparticles: A comprehensive review. International Journal of Polymeric Materials and Polymeric Biomaterials. 2017; 67(6), 383–400. https://doi.org/10.1080/00914037.2017.1332623

11.   Katrolia A, Chauhan SB, Shukla VK. Formulation and evaluation of metformin hydrochloride-loaded curcumin–lycopene niosomes. SN Applied Sciences. 2019 Dec; 1:1-6. DOI: https://doi.org/10.1007/s42452-019-1768-6

12.   Bhardwaj P, Tripathi P, Gupta R, Pandey S. Niosomes: A review on niosomal research in the last decade. Journal of Drug Delivery Science and Technology. 2020 Apr 1; 56: 101581. DOI: https://doi.org/10.1016/j.jddst.2020.101581

13.   Gharbavi M, Amani J, Kheiri-Manjili H, Danafar H, Sharafi A. Niosome: A Promising Nanocarrier for Natural Drug Delivery through Blood-Brain Barrier. Advanced Pharmacology of Science. 2018: 1-6. DOI: https://doi.org/10.1155/2018/6847971

14.   Sharma Rajni, DuaJagdeep Singh, Prasad D.N, Hira Shabnam, Monika. Advancement in Novel Drug Delivery System: Niosomes. Journal of Drug Delivery & Therapeutics. 2019; 9(3-s):995-1001. DOI: 10.22270/jddt.v9i3-s.2931

15.   Kaul S, Gulati N, Verma D, Mukherjee S, Nagaich U. Role of nanotechnology in cosmeceuticals: a review of recent advances. Journal of Pharmaceutics. 2018; 2018(1):3420204. DOI: 10.1155/2018/3420204

16.   Arshad, N., Shaheen, F., Khan, I. N., Naeem, S., Riaz, M., Siddique, M. I., Waqar, M. A. A comprehensive review on niosomes: novel manufacturing techniques, factors influencing formation, applications and recent advances. International Journal of Polymeric Materials and Polymeric Biomaterials. 2024:1–18. https://doi.org/10.1080/00914037.2024.2426611

17.   Liga S, Paul C, Moacă E-A, Péter F. Niosomes: Composition, Formulation Techniques, and Recent Progress as Delivery Systems in Cancer Therapy. Pharmaceutics. 2024; 16(2):223. DOI: https://doi.org/10.3390/pharmaceutics16020223

18.   Ge X, Wei M, He S, Yuan WE. Advances of Non-Ionic Surfactant Vesicles (Niosomes) and Their Application in Drug Delivery. Pharmaceutics. 2019 Jan 29; 11(2):55. DOI: 10.3390/pharmaceutics11020055 .

19.   Kaur P, Rani R, Singh AP, Singh AP, An Overview of Niosomes, Journal of Drug Delivery and Therapeutics. 2024; 14(3):137-146. DOI: http://dx.doi.org/10.22270/jddt.v14i3.6450

20.   González-Rodríguez ML, AM Rabasco. Charged liposomes as carriers to enhance the permeation through the skin. Expert Opinion on Drug Delivery.2011; 8(7): 857- 871. DOI: https://doi.org/10.1517/17425247.2011.574610

21.   Shewaiter MA, Selim AA, Moustafa YM, Gad S, Rashed HM. Radioiodinated acemetacin loaded niosomes as a dual anticancer therapy. International Journal of Pharmaceutics. 2022 Nov 25; 628: 122345. DOI: 10.1016/j.ijpharm.2022.122345

22.   Uchegbu I, Vyas S. Non-ionic surfactant-based vesicles (niosomes) in drug delivery. International Journal of Pharmaceutics. 1998; 172(2):33–70. DOI: https://doi.org/10.1016/S0378-5173(98)00169-0

23.   Baillie A, Coombs G, Dillan G, Laurio J. Non-ionic surfactant vesicles, niosomes as a delivery system for the anti-leishmanial rug Sodium stibogluconate. Journal of Pharmacy and Pharmacology. 1980; 38(2):502. DOI: https://doi.org/10.1111/j.2042- 7158.1986.tb04623.x

24.   Moammeri A, Chegeni MM, Sahrayi H, Ghafelehbashi R, Memarzadeh F, Mansouri A, Akbarzadeh I, Abtahi MS, Hejabi F, Ren Q. Current advances in niosomes applications for drug delivery and cancer treatment. Materials Today Bio. 2023 Dec 1; 23: 100837. DOI https://doi.org/10.1016/j.mtbio.2023.100837

25.   Prabhu, kumar R, Koland, dhondge, Preparation and evaluation of nanovesicles of Brominide tartrate, Journal of Young Pharmacist. 2010; 2(4): 356-361. DOI: https://doi.org/10.4103/0975-1483.71623

26.   Indu pal K, Manjit S, Meenakshi K. Formulation and evaluation of ophthalmic preparations of acetazolamide, International Journal of Pharmaceutics. 1999: 119-127. DOI: https://doi.org/10.1016/S0378-5173(00)00359-8

27.   Ma A, Stephanie WY, Wong JK. Micropulse laser for the treatment of glaucoma: a literature review. Survey of ophthalmology. 2019 Jul 1; 64(4): 486-97. DOI: https://doi.org/10.1016/j.survophthal.2019.01.001

28.   Bourcier T, Sauer A, Dory A, Denis J, Sabou M. Fungal keratitis. Journal Francais D'ophtalmologie. 2017 Nov 1; 40(9): e307-13. DOI: 10.1016/j.jfo.2017.08.001

29.   McClements ME, MacLaren RE. Gene therapy for retinal disease. Translational Research. 2013 Apr 1; 161(4):241-54. DOI: 10.1016/j.trsl.2012.12.007

30.   Gugleva V, Titeva S, Rangelov S, Momekova D. Design and in vitro evaluation of doxycycline hyclate niosomes as a potential ocular delivery system. International Journal of Pharmaceutics. 2019 Aug 15; 567, 118431. DOI: 10.1016/j.ijpharm.2019.06.022

31.   Lambert G, Guilatt RL. Current ocular drug delivery challenges. Drug Dev Report Industry Overview Deals. 2005; 33: 1-2. DOI: https://doi.org/10.3390/pharmaceutics15010205

32.   Lang JC. Ocular drug delivery conventional ocular formulations. Advanced Drug Delivery Reviews. 1995 Aug 1; 16(1):39-43. DOI: https://doi.org/10.1016/0169-409X(95)00012-V

33.   Saettone MF, Giannaccini B, Ravecca S, La Marca F, Tota G. Polymer effects on ocular bioavailability—the influence of different liquid vehicles on the mydriatic response of tropicamide in humans and in rabbits. International Journal of Pharmaceutics. 1984 Jan 1; 20(1-2):187-202. DOI: https://doi.org/10.1016/0378-5173(84)90229-1

34.   Baranowski P, Karolewicz B, Gajda M, Pluta J. Ophthalmic drug dosage forms: characterisation and research methods. The Scientific World Journal. 2014; 2014(1):861904. DOI: 10.1155/2014/861904

35.   Sahoo SK, Dilnawaz F, Krishnakumar S. Nanotechnology in ocular drug delivery. Drug Discovery Today. 2008 Feb 1; 13(3- 4):144-51. DOI: https://doi.org/10.1016/j.drudis.2007.10.021

 

 

 

 

Received on 04.01.2025      Revised on 03.05.2025

Accepted on 29.07.2025      Published on 10.04.2026

Available online from April 13, 2026

Asian J. Res. Pharm. Sci. 2026; 16(2):117-125.

DOI: 10.52711/2231-5659.2026.00019

©Asian Pharma Press All Right Reserved

 

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.