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Abstract

A new medicine delivery method called niosomes involves encapsulating the drug in a vesicle. Niosomes get their name from the fact that the vesicle is made up of a bilayer of non-ionic surface-active substances. Niosomes and liposomes share a structural similarity in that they are both composed of a bilayer. Instead of phospholipids, like in the case of liposomes, the bilayers of niosomes are composed of non-ionic surface-active substances. When submerged in water, the majority of surface-active agents form micellar structures; nevertheless, certain surfactants can form niosome-like bilayer vesicles. Both hydrophilic and lipophilic medications can be captured by niosomes, which can also prolong the drug's circulation throughout the body. It is anticipated that encapsulating a drug in a vesicular system may increase its penetration into the target tissue, prolong its time in the systemic circulation, and possibly lessen toxicity if selective absorption is possible. Niosomes addressed the problems of drug instability, insolubility, low bioavailability, and rapid degradation. This study provides an overview of the niosome production process and its uses in the pharmaceutical industry. The advantages, disadvantages, preparation techniques, influencing factors, characterisations, formulation component, and applications of noisome are the main topics of this review study.

Keywords

Niosomes compositions, Preparation methods, Factors affecting, and Applications.

Introduction

Novel Drug Delivery Systems (NDDS), which are crucial to drug research and discovery and should ideally meet two conditions, have seen substantial modern advancements during the last three decades [1]. First, during the course of treatment, it should release the medication at a pace determined by the body's needs. Second, the active chemical entity ought to be transported to the site of action. Drug delivery systems employing nanosized vesicles, provide noticeable advantages and benefits over traditional and conventional dosage forms due to the absence of any drug's reservoir property. A targeted drug delivery system reduces the interaction of medication in non-targeted tissues by administering active compounds at site of action [2]. To put it simply, drug targeting is the process of directing a therapeutic agent straight to the desired location without causing the agent to interact with other nearby tissues. Because of their potential to transport medications, genetic material, vaccinations, and nutraceuticals, niosomes have been the subject of substantial scientific research in the pharmaceutical industry [3]. This is due to their versatility in changing surface properties, which permits regulated discharge, targeted delivery, and enhanced therapeutic efficacy. They are useful in many different sectors, including but not limited to dermatology, cancer treatment, and vaccination administration [4].

The Genesis Of Niosomes

In 1975, L'Oreal created and patented the first niosome formulations. Drug delivery for anticancer medications was the initial application of niosomes [5]. The discovered niosome formulations had the ability to modify methotrexate's pharmacokinetic profile, organ distribution, and metabolism in mice. Niosomes can entrap hydrophilic pharmaceuticals in aqueous compartments or lipophilic drugs by partitioning these molecules into a bilayer domain; their size, shape, and structure are all variable. It is also possible to formulate them as multilamellar, oligolamellar, or unilamellar vesicles. Additionally, niosomes are rather simple for routine and large-scale production, have good physical stability, and are reasonably priced. Presenting the basics of niosome creation and characterisation together with an explanation of their application in drug delivery with a focus on more recent research is the goal of this review. An overview of the growing interest in niosomes in the field of medication delivery will be given in this article.[6]

Niosomes

Medications can be integrated into niosomes because they are a unique drug delivery system that traps hydrophilic drugs in the core cavity and hydrophobic drugs in the non-polar region found within the bilayer [7]. Because of their ampiphillic character, niosomes get their name from the fact that the drug is enclosed in a vesicle made of non-ionic surfactant. Niosomes are extremely tiny and microscopic. Niosomes are divided into three categories: big unilamellar vesicles, tiny unilamellar vesicles, and multilamellar vesicles. Below is a description of the several kinds of niosomes:

1. Multilamellar Vesicles (MLVs): These are made up of many bilayers that surround the aqueous lipid compartment independently. These vesicles range in diameter from 0.5 to 10 ?m. These vesicles work very well as medication carriers for substances that are lipophilic.

2. Large Unilamellar Vesicles (LUV): These niosomes can entrap higher amounts of bioactive molecules with a very efficient utilisation of membrane lipids because of their high aqueous/lipid compartment ratio [8].

 3. Small Unilamellar Vesicles (SUV): The most common methods for creating these tiny unilamellar vesicles include sonication, French press extrusion, and homogenisation from multilamellar vesicles. Small unilamellar vesicles range in dimension from 0.025 to 0.05 ?cm. They are prone to aggregation and fusion and are thermodynamically unstable. They have a modest entrapped volume and a low proportion of aqueous solute entrapment [9].

The Positive Attributes Of Niosomes [10]

1. L'Oreal was the first to use niosomes in cosmetics because they provided the following benefits.

2. Compared to oil-based methods, the water-based vesicle suspension delivers higher patient compliance.

3. A wide range of pharmaceuticals can be employed since the niosome's structure provides space for hydrophilic, lipophilic, and amphiphilic drug moieties.

4. Depending on the need, the vesicle's properties, including size and lamellarity, can be changed.

5. The vesicles can serve as a depot to provide a controlled and gradual release of the medication.

Drawbacks Of Niosomes

In certain instances, non-ionic surfactants may interact with other elements in the system, causing the formulation to become non-homogeneous or resulting in the formation of precipitates.

Construction Of Niosomes

A vesicle-forming amphiphile, or non-ionic surfactant like Span 60, which is often stabilised by the addition of cholesterol and a little quantity of anionic surfactant, like dicetyl phosphate, which also aids in stabilising the vesicle, would make up a normal niosome vesicle.

       
            FIG-1.png
       

Typical structure of niosomes [11]

Formulation Aspects Of Niosomes [12]

1. Non-ionic surfactants

A significant part of niosome structure, non-ionic surfactants are better than anionic and cationic surfactants in terms of toxicity, stability, and compatibility. Non-ionic surfactants stimulate cell surfaces and are less haemolytic and hazardous. Additionally, they keep the solution's pH at a physiological level. A hydrophilic end and a lipophilic end are two separate areas that make up non-ionic surfactants, which are regarded as amphiphilic molecules. These two components are typically joined by amide, ester bonds, or ether. The creation of the vesicles' bilayer structure is determined by the surfactant's hydrophilic–lipophilic balance (HLB) [13]. An essential component in regulating vesicle entrapment is the HLB value. It is also well known that this dimensionless factor can be used as a time-efficient surfactant selection guide. The HBL range for non-ionic surfactants spans from 0 to 20. An HBL value between 14 and 17 is unsuitable for generating niosomes, while the optimal entrapment efficiency is achieved at an HBL value of 8.6. As the HBL decreases from 8.6 to 1.7, the encapsulation efficiency diminishes. Examples: 1. Spans (span 60, 40, 20, 85, 80) 2. Tweens (tween 20, 40, 60, 80). 3. Brijs (brij 30, 35, 52, 58, 72, 76)

2. Cholesterol

Steroids, such as cholesterol (CHOL), enhance the structure and characteristics of non-ionic vesicles, making them essential for niosome formation. Research indicates that cholesterol positively influences rigidity, permeability, leakage, and entrapment efficiency. Cholesterol is an amphiphilic compound, which means the hydroxyl (OH) group is oriented towards the aqueous phase while the hydrocarbon surfactant tail is directed towards the aliphatic chain. When the fundamental structure of cholesterol integrates into the niosome bilayer, it increases rigidity by restricting the movement of the hydrocarbon chains, which is beneficial under high-stress conditions [14]. The incorporation of cholesterol in niosome preparation also reduces permeability to harmful effects from plasma and serum components, resulting in lower leakage rates. The permeability of niosomes made with 5, 6-carboxy fluorescein (CF) decreases tenfold upon the incorporation of cholesterol into the formulation. A non-ionic hydrophilic surfactant like decyl polyglycolide can only create a stable, spherical vesicle when a large amount of CHOL is present [15]. Consequently, CHOL enhances the stability of the niosomal membrane. When the HLB value exceeds 10, it is necessary to increase the minimum concentration of cholesterol to accommodate the larger head groups of the surfactant. Niosomes containing a greater amount of CHOL display improved entrapment efficiency, whereas there was no significant increase observed in the Brij 52 (HLB 5.3) niosomes. In fact, once a specific cholesterol proportion is surpassed, the efficiency of trapping begins to decline [16].

3. Hydration medium

The choice of hydration medium significantly influences the formation of niosomes, as it directly affects particle size. In niosome formulation, phosphate buffers with different pH levels are commonly used as hydration media. The pH of the hydration medium is determined by the solubility of the active ingredient being encapsulated [17].

Method Of Preparation Of Niosomes

1) Thin film hydration technique

The mixture of vesicle forming ingredients like surfactant and cholesterol are dissolved in a volatile organic solvent (diethyl ether or chloroform) in a round bottom flask. The organic solvent is removed at room temperature (400 C) using a rotary evaporator, leaving a thin layer of solid mixture deposited on the wall of round bottom flask. The dried surfactant film can be rehydrated with aqueous phase at (50°C-60°C) with gentle agitation. This process forms typical multilamellar niosomes. Hydrating the lipid above phase transition temperature of surfactant and vortexing during hydration helps to reduce the size of vesicles prepared by thin film hydration [18].

2) Ether injection method

This method provides a means of making niosomes by slowly introducing solution of surfactants dissolved in diethyl ether into warm water maintained at (60°C). Typically, the surfactant mixture is injected through a 14-gauge needle into an aqueous solution of the material to be encapsulated at (60°C). Vaporization of ether leads to formation of single layered vesicles. Depending on the conditions used, the diameters of the resulting vesicles range from 50 to 1000 nm. This method produces unilamellar vesicles showing highest entrapment efficiency [19].

3) Sonication

The purpose of Sonication is to reduce the vesicle size. Increase in sonication time results in concomitant reduction in vesicle diameter. Multilamellar vesicles. Formed by thin film hydration method are sonicated either with probe sonicator or bath type sonicator. Probe sonication leads to more rapid size reduction How ever, heat production, metal particle shedding from probe tip, and aerosol generation present problems. Temperature can be accurately regulated in bath type sonicator. Also, for larger volume samples bath type sonicator is consider to be suitable. The finished products, i.e. vesicles are unilamellar in shape. Great care must be taken while working with a temperature sensitive solute. Also, direct sonication of lipid mixture and aqueous phase can be carried out to obtain niosomes [20].

4) Micro-fluidization

Micro-fluidization is the recent technique used to prepare unilamellar vesicles of defined size distribution. This method is based on submerged jet principle in which two fluidized streams interact at ultra-high velocities (up to 1700ft/sec) in precisely defined micro channels within the interaction chamber. The impingement of thin liquid sheets along a common front is arranged such that the energy supplied to the system remains within the area of niosomes formation. The result is greater uniformity, smaller size and better reproducibility in device saleable to commercial production [21].

5.The pH gradient of the transmembrane (inside acidic) The process of drug uptake (remote loading): Chloroform dissolves cholesterol and surfactant. After that, the solvent is evaporated at lower pressure, leaving a thin layer on the flask's round bottom wall. Through vertex mixing, 300 mm citric acid (pH 4.00) is added to the solid to hydrate it. After being frozen and shared three times, the multilamellar vesicles are subsequently sonicated. To this suspension of niosomes. After adding 10 mg of medication per millilitre to an aqueous solution, vortexing is done. After that, 1M disodium phosphate is added to the sample to bring its PH up to 7.087.2. After that, this mixture is heated for ten minutes at 60°C to produce niosomes [22].

6. The "Bubble" Method:

It is a brand-new method that eliminates the need for organic solvents in the one-step production of liposomes and niosomes. The round bottomed flask with three necks that are submerged in a water bath to regulate the temperature makes up the bubbling unit. The first and second necks include a water-cooled reflux and thermometer, while the third neck supplies nitrogen. At 70°C, cholesterol and surfactant are combined in this buffer (pH 7.4), mixed for 15 seconds with a high shear homogeniser, and then 'bubbled' at 70°C with nitrogen gas [23]

Elements Impacting Niosome

Numerous factors influence the niosome's chemical and physical properties as well as how vesicles form. Characteristics of drugs the vesicular capabilities are affected by the drug's nature [24].

1. Drug properties

The drug's molecular weight, chemical structure, lipophilicity, hydrophilicity, and HLB value all affect niosome size. The drug's entrapment efficiency is likewise impacted by the HLB value. As vesicle size increases, so does drug trapping in niosomes. One Drug entrapment in the niosome causes an interaction between the solute charge and the surfactant head group, which results in repulsion and an increase in vesicle size. Thus, several drugs added to polyethylene glycol-coated vesicles lessen their tendency to enlarge [25].

2. Hydration temperature

The temperature at which the pro-niosome is hydrated affects the niosome's size and form. The polyhedral vesicle of C16G2: Solulan C24 (91:9) is based at 25°C, but at 45°C it transforms into a spherical vesicle, and when it cools, it forms a cluster of smaller spherical niosomes at 55–49°C [26].

3. Amount and type of surfactant

With increase in the HLB of surfactants like Span 85 (HLB 1.8) to Span 20 (HLB 8.6), the mean size of noisome enhances proportionally as surface free energy reduces with an increase in hydrophobicity of surfactant. The bilayers of the vesicles are either called liquid state or in gel state, depending on the temperature, the type of lipid or surfactant and the presence of other components such as cholesterol [27].

4. Methods of Preparation

The majority of the scientists examined several niosome preparation techniques, including ether injection, sonication, and hand shaking. Compared to the ether injection approach (50-1000 nm), the hand shaking method creates vesicles with a larger diameter (0.35-13 nm). The technique of reverse phase evaporation (REV) can be used to create small niosomes. The micro-fluidization technique produces vesicles that are smaller and more homogenous. By using a transmembrane pH gradient (within an acidic) drug uptake pathway, Parthasarthi et al. produced niosomes. Niosomes produced with this technique demonstrated improved drug retention and increased entrapment efficiency [28]

5. Resistance to Osmotic Stress

When a hypertonic salt solution is added to a noisome suspension, the niosomes' diameter decreases. The vesicles in a hypotonic salt solution first release slowly and somewhat swell, most likely as a result of the eluting fluid being inhibited. This is followed by a quicker release, which could be brought on by the vesicles' structure mechanically loosening under osmotic stress [29].

Characterization

1. Zeta Potential

Zetasizer and DLS tools can be used to measure the surface zeta potential of niosomes. The behaviour of niosomes is significantly influenced by their surface charge. Compared to uncharged vesicles, charged niosomes are often more durable against aggregation. et al Bayindir and Yuksel synthesised niosomes loaded with paclitaxel and examined their physicochemical characteristics, including their zeta potential. They discovered that negative zeta potential levels between -41.7% and -58.4% are high enough to stabilise niosomes electrostatically [30].

2. Stability

 By measuring the mean vesicle size, size distribution, and entrapment efficiency during several months of storage at various temperatures, one can assess the stability of niosomes. The niosomes are sampled periodically throughout storage, and UV spectroscopy or HPLC techniques are used to determine the proportion of medication that is preserved in the niosomes [31].

3. Entrapment efficiency

 The drug that remains entrapped in niosomes is identified by complete vesicle disruption using 50% n-propanol or 0.1% Triton X-100, and the resultant solution is analysed using the proper assay method for the drug [32]. The entrapment efficiency of the niosomal dispersion can be achieved by separating the unentrapped drug using dialysis centrifugation or gel filtration [33].

4. Sem

Microscopy with scanning electrons one crucial feature of niosomes is their particle size. Scanning Electron Microscopy (SEM) was used to examine the size distribution of niosomes as well as their surface morphology, including their roundness, smoothness, and aggregate formation. The double-sided tape that was attached to aluminium stubs was sprayed with niosomes [34].

5. In-vitro release

Dialysis tubing is a commonly used technique to investigate in-vitro release. After being cleaned, distilled water is used to immerse a dialysis bag. The drug-loaded niosomal suspension is moved into this bag after 30 minutes [35]. The vesicle-containing bag is submerged in buffer solution at either 25°C or 37°C while being continuously shaken. Samples were taken out of the outer buffer (release medium) at predetermined intervals and put back in with an equivalent volume of brand-new buffer. An appropriate assay method is used to determine the drug content of the samples [36].

Applications

1) Niosomes as a drug carrier and targeting

Additionally, iobitridol, a symptomatic operator used in X-ray imaging, has been transported by niosomes. Topical niosomes can act as an entry enhancer, a neighbourhood station for the continuous delivery of dermally dynamic mixes, a solubilisation grid, or a rate restricting layer blockage for the modification of foundational drug absorption [37]. The potential of niosomes to target medications is among their most advantageous features. Drugs can be targeted to the Reticuloendothelial system using niosomes. Niosome vesicles are preferentially absorbed by Reticulo-Endothelial System (RES).  Circulating blood factors known as opsonins regulate the uptake of niosomes. The niosome is marked for clearing by these opsonin [38]. Drugs with this localization are used to treat tumours in animals that have a history of spreading to the liver and spleen. This medication localisation can also be used to treat liver parasite infections. Additionally, they can be used to target medications to organs other than the RES. Since immunoglobulins bind easily to the lipid surface of niosomes, a carrier system (like antibodies) can be linked to niosomes to direct them to specific region [39].

Oral drug delivery

Most medications are best administered orally; however, most recently developed and currently marketed medications that are administered orally frequently have bioavailability issues for a variety of reasons, including low solubility and dissolution rate, unpredictable absorption, inter- and intra-subject variability, and lack of dose proportionality [40]. A number of techniques, such as complexation, drug derivatisation, solid state manipulation, surfactant addition, surface area enhancement through micronization or nanonization, spray drying, and microencapsulation, have been used to enhance the dissolving behavior of insoluble medications [41]. SVs from Span 40, Span 60, and CHOL have recently been suggested as viable oral delivery methods for the efficient administration of ganciclovir. Rats used in an in-vivo study showed that oral delivery of the medication increased its bioavailability five times more than tablet administration. A common firstline treatment for type II diabetes is metformin, an oral hypoglycemic that must be taken at extremely high doses two to three times per day [42]. In addition, it has a number of adverse effects, including lactic acidosis, stomach discomfort, chest pain, and allergic responses. Niosomal formulations including Span 60, Span40, and CHOL in an equimolar ratio were suggested as a way to reduce the frequency of doses and side effects associated with metformin. In order to overcome valsartan proniosomes' low absolute bioavailability (25%) brought on by their poor aqueous solubility, gastrointestinal side effects, and the fact that two thirds of the dose is eliminated by renal and biliary transport, oral administration of the drug was also investigated [43]. Jukanti et al. described the creation and properties of proniosomal powders based on maltodextrin loaded with valsartan. Ex-vivo tests on the rat gut to evaluate valsartan permeation from proniosomes revealed a notable increase in penetration throughout the rat gut, indicating the possibility of proniosome carriers for better oral valsartan delivery [44].

  1. Ocular drug delivery

Because of tear formation, corneal epithelial impermeability, nonproductive absorption, and short residence duration, it is challenging to obtain high bioavailability of drugs from ocular dosage forms such as ophthalmic solution, suspension, and ointment. In order to attain a high level of medication bioavailability, niosomal vesicular systems have been suggested [45]. In contrast to a basic sodium stibogluconate solution, Carter et al. showed that serial treatment with sodium stibogluconate loaded niosomes was effective against parasites in the liver, spleen, and bone marrow. When compared to the drug solution, niosomal formulations made with different surfactants (Tween20, Tween60, Tween80, or Brij 35) demonstrated a slower in-vitro release of gentamicin or enhanced absorption of cyclopentolate by preferentially altering the permeability properties of the scleral and conjunctival membranes [46]. Oval gigantic niosomes based on Span60 have recently been shown to be nearly non-irritating and to be able to regulate the penetration of naltrexone hydrochloride while also increasing its corneal permeability [47]. The study assessed the spreading, rheological characteristics, and capacity to stop NTX autoxidation in aqueous solutions of NSVs and discomes for ocular delivery of NTX. Compared to the aqueous solution, the produced niosome formulation had a noticeably higher viscosity [48]. The primary variables influencing the viscosity of the niosomal dispersions were the size, composition, and lipid content of NSVs. When compared to free NTX solutions, the produced formulations were able to significantly protect the encapsulated NTX from the photo-induced oxidation, whereas exposure to artificial daylight illumination can cause severe oxidation-induced degradation of NTX. The niosomes under investigation demonstrated a possible ocular delivery system for NTX [49].

Dermal and transdermal drug delivery

The benefit of this strategy is that it allows for the localisation of high drug concentrations at the site of action, minimising systemic absorption and so lowering systemic adverse effects. Conversely, transdermal medication delivery employs the skin as an alternate pathway for the medicine to enter the bloodstream [50].  The following are some benefits of this drug delivery method over traditional oral and parental routes: no gastrointestinal degradation (pH, enzymatic activity, drug interaction with food, beverages, and other oral drugs); avoidance of first pass hepatic metabolism (avoiding the deactivation by digestive and liver enzymes), which increases drug bioavailability and efficacy; and substitution of oral administration when such a route is inappropriate [52]. It was recently suggested that ibuprofen be applied topically using pH-sensitive NSVs made with Tween 20 or Span 60 combined with CHOL and cholesteryl hemisuccinate (CHEMS), a derivative of cholesterol that is a pH-sensitive molecule [53]. The drug's in-vitro skin penetration was significantly increased only by niosomes containing Span 60 and CHEMS. Gallidermin, terbinafine, curcumin, vinpocetine, ellagic acid, and ammonium glycyrrhizinate were among the other medications incorporated into niosomes for topical delivery [54].

  1. Pulmonary drug delivery

The therapeutic benefit of pulmonary administration may outweigh that of oral or parenteral administration in cases of inflammatory disorders, infections, or respiratory tract malignancy [55]. Additionally, lipophilic drugs, like corticosteroids, can be significantly hindered in their ability to reach their receptors, which are located within the cytoplasm of bronchial epithelial cells, in illnesses marked by hypersecretion of bronchial mucus. In order to get around this issue, surfactant vesicles were suggested [56]. Several research teams assessed the effects of niosomal administration of beclomethasone dipropionate (BDP) in asthma and chronic obstructive pulmonary disease. Using an Omron MicroAir (passively vibrating mesh) nebuliser, an Aeroneb Pro (actively vibrating mesh) nebuliser, and a Pari LC print (air-jet) nebulizer, the Span 60 niosomes which were isolated from the equivalent proniosomes were characterized and their aerosol delivery examined [57]. All evaluated devices produced aerosols with high drug yield and fine particle fraction (FPF). The Aeroneb Pro vibrating-mesh nebulizer's medication production and FPF were comparable to those of the Pari LC sprint, a typical airjet nebuliser. The usefulness of niosomes as liposome substitutes for pulmonary administration requires further in-vivo research [58].

  1. Parenteral delivery

One of the best ways to distribute the active ingredients in pharmaceuticals is by parenteral administration. Frequent injections are necessary to maintain a therapeutic effective concentration of a medicine, which eventually results in low patient compliance [59]. Significant advancements were made in the field of vesicular formulation technologies for parenteral drug delivery, which were typically able to provide a predictable, targeted, and sustained drug release to get around the issues with traditional parenteral delivery systems, particularly for medications with low bioavailability and a narrow therapeutic index [60]. For the treatment of melanoma, niosomes hold significant promise in therapeutic nanoformulations. To overcome multidrug resistance in a human lung cancer cell line resistant to PTX, new nanohybrid systems of lipid loading paclitaxel and non-ionic surfactant were created. Span 40 and CHOL were used to create cisplatin-loaded niosomes (CP-NMs), which were lyophilised and subsequently described. Rabbits with VX2 sarcoma were used to investigate their antitumor activity [61]. When compared to rabbits treated in the same manner with the drug solution, the rabbits locally injected with CP-NMs showed significantly better results in terms of tumour growth inhibition, significantly lower mortality, improved body weight variation, and inhibition of tumour metastases to the liver and inguinal lymph nodes. The promising anticancer outcomes suggested that CP-NMs may be created as a low-toxicity, potent anticancer preparation [62].

Peptide Drug Delivery

Peptide Drug Delivery The problem of avoiding the enzymes that would break down the peptide has long plagued oral peptide medication administration [63]. Research is being done on the effective use of niosomes to shield the peptides from gastrointestinal peptide degradation. A vasopressin derivative entrapped in niosomes was administered orally as part of an in-vitro investigation, which revealed that the drug's entrapment greatly improved the peptide's stability [64].

Insulin

At in-vitro, insulin-entrapped niosomes made of cholesterol and Brij92 at a molar ratio of 7:3 demonstrated a high level of stability against the proteolytic activity of trypsin, pepsin, and ?-chymotrypsin [65]. These findings suggest that niosomes may be created as oral dosage forms with sustained release for the administration of proteins and peptides.

oligonucleotide         

The oligonucleotide to increase the stability and cellular distribution of oligonucleotides (OND), cationic niosomes modified with polyethylene glycol (PEG) were employed. As gene carriers, PEGylated cationic niosomes, which are made up of DC-Chol, PEG2000-DSPE, and the non-ionic surfactant Span, have certain benefits [66]. A neutral zeta potential was observed in PEGylated cationic niosome and OND complexes with a particle size of roughly 300 nm. PEG modification inhibited particle aggregation in serum and dramatically reduced serum protein binding. Serum nuclease resistance was elevated in the loaded nuclear acid medication [67]. PEGylated cationic niosomes are prospective drug delivery vehicles for increased OND potency in-vivo since they demonstrated a better efficiency of OND cellular absorption in serum when compared to cationic niosomes [68].

Delivery of Vaccines

Formulations based on non-ionic surfactant vesicles (niosomes), which are only immunogenic once a week, make up an intriguing class of vaccine carrier systems. Niosomes are becoming more and more popular for topical vaccination and as a means of delivering vaccines orally [69]. The effects of different ratios of cholesterol, surfactant, and dicetyl phosphate on niosome morphology, particle size, entrapment effectiveness, and in-vitro antigen release were examined. When the immune-stimulating activity was examined, topical niosomes were shown to produce similar amounts of endogenous cytokines and serum antibody titers as topical liposomes and intramuscular recombinant HBsAg [70].

3) Natural product delivery

To encapsulate curcumin, various proniosomal gel bases were made with Span 60, Span 80, Tween 20, and CHOL. The studied formulation exhibited less anti-inflammatory and anti-arthritic properties than the commercially available indomethacin products, but it was neither poisonous nor irritating [71]. Despite being a strong antioxidant phytochemical, ellagic acid (EA) has little uses because of its poor biopharmaceutical characteristics (low permeability and low solubility). Span 60 and Tween 60 mixes were used to create EA-loaded niosomes for transdermal administration. According to research on skin distribution, EA-loaded niosomes were more effective than EA solutions at delivering EA through the human epidermis and dermis [72]. When compared to the parent extract, niosome formulations containing Gymnema sylvestre extract demonstrated a significant decrease in blood glucose levels and an increase in antihyperglycemic action [73]. A silymarin niosomal preparation was suggested based on the low bioavailability of silymarin and the benefits of niosomes. In albino rats, this preparation significantly reduced serum alkaline phosphatase and transaminase levels when compared to silymarin suspension. Niosomes may be viewed as prospective carriers by various routes of administration in pharmaceutics, cosmetics, and food applications as a result of the growing number of studies on natural products [74].

4) Bioavailability Enhancement

Promoting Bioavailability Drugs like acyclovir, which are entrapped in niosomes made using the fil hydration process, exhibit increased bioavailability when niosomes are used to boost their bioavailability. Following encapsulation in niosomes, a notable increase in griseofulvin bioavailability has been observed. Niosomal preparations of medications, including doxorubicin, cefixime, levofloxacin, and fluconazole, have also been demonstrated in other studies to improve their bioavailability [75]. A study by Vadlamudi et al. (2014) also demonstrated that glibenclamide's pharmacokinetic profile and bioavailability were enhanced by niosomes [76].

5) Imaging Diagnostics

Imaging Diagnostics These days, niosomes are employed in diagnostic imaging. These days, gadobentane niosomes are being employed in diagnostic imaging. Iopromide radiopaque niosomes' effects in vivo have also been the subject of another investigation [77]. When given intravenously, iopromide niosomes were found to concentrate on the kidney. It has been demonstrated that iobitridol, another diagnostic drug used for X-ray imaging, works well when contained in niosomes. Diagnostic imaging agents can be contained within niosomes, guaranteeing stability and regulated imaging payload discharge. It may be possible to increase imaging contrast and imaging length using this regulated discharge [78].

6)   Niosomes versus liposomes

Liposomal versus niosomes Given the vast potential of vesicular systems for drug delivery and targeting, there is growing interest in comparing the potential advantages of niosome entrapment to liposomes, in addition to more general factors like lower costs and greater resistance to oxidative degradation [79]. The majority of published findings focus on vesicles' capacity to improve percutaneous penetration, hence boosting medication efficacy following topical delivery. When compared to liposomes, formulations containing niosomes showed superior stability, sustained release properties, and skin penetration capability [80]. However, investigations comparing the topical delivery of anticancer drugs to cancer cells using liposomes and niosomes produced conflicting findings. Niosomal CPO, as opposed to liposomal and pure CPO, showed a cytotoxic effect at significantly lower concentrations selectively on cancer cells (KB-oral cancer, PC3-prostate cancer, Siha-cervical cancer, and Vero-kidney epithelial cell lines) when ciclopirox olamine (CPO) was encapsulated in liposomes and niosomes, enhancing CPO's anticancer potential [??2;]. However, when liposomes and niosomes were compared for topical delivery of 5-fluorouracil (5-FU) to skin cancer cells (HaCaT), it was discovered that liposomes were more harmful to the cell line than niosomes [??2;].

Additional Uses

Long-Term Release Drugs with low therapeutic index and limited water solubility can benefit from the sustained release action of niosomes because niosomal encapsulation can keep them in circulation [??3;]. Localized effect of drugs given that niosomes are small and have a poor penetration rate into connective tissue and epithelium, they are one method of delivering drugs that results in localized drug action [??].

CONCLUSION

It has been demonstrated that niosomes can be helpful in regulated drug delivery systems for oral, parenteral, transdermal, and ocular routes. They can be used to encapsulate anti-inflammatory, anti-cancer, and anti-infective substances. More recently, they have been employed as adjuvants in vaccines. Niosomes could be used as diagnostic imaging agents and allow for the targeting of specific regions of mammalian beings. In terms of stability, toxicity, and cost-effectiveness, niosomes are better systems than other carriers. Since maintaining the biological potential of the formulations requires maintaining encapsulation efficiency, the issue of drug loading still needs to be addressed, even though several novel solutions have been devised to address it. One of the most crucial factors influencing the vesicle formation, toxicity, and stability is the type of surfactant used; therefore, surfactants with a higher phase transition should be chosen since they produce more acceptable permeability and toxicity profiles. For niosomal uses, transdermal, peroral, parenteral, and ocular routes are appropriate. Niosome applications as radiodiagnostic agents and vaccines have recently been investigated and shown to be promising. Given that niosomes can encapsulate both hydrophobic and hydrophilic medications, care should be taken when choosing a medication to be administered via niosomes.

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  3. Uchegbu IF, Florence AT. Non-ionic surfactant vesicles (niosomes): physical and pharmaceutical chemistry. Adv Colloid Interface Sci., 1995; 58: 1–55.
  4. Bouwstra JA, Van HD, Hofland HE. Preparation and characterization of non ionic surfactant vesicles. Colloids Surf A Physicochem Eng Asp., 1997; 80: 123-4.
  5. Rangasamy M, Ayyasamy B, Raju S, Develly SG, Shaik S. Formulation and in-vitro evaluation of noisome encapsulated acyclovir. J Pharm Res., 2008; 1: 163-6.
  6. Ijeoma F., Uchegbu., Suresh P., Vyas., Non-ionic surfactant based vesicles (niosomes) in drug delivery. Int. J. Pharm., 1998; 172: 33–70.
  7. Malhotra M., Jain N.K., Niosomes as Drug Carriers. Indian Drugs, 1994; 31(3): 81-866.
  8. Alsarra A., Bosela A,, Ahmed S.M,, Mahrous G.M., Proniosomes as a drug carrier for transdermal delivery of ketorolac. Eur. J. Pharm. and Biopharm,2004; 2(1): 1-6.
  9. Hu C., Rhodes D.G., Proniosomes: a novel drug carrier preparation. Int. J. Pharm. 1999, 185: 23-35.
  10. Blazek-Walsh A.I., and Rhodes D.G., Pharm. Res. SEM imaging predictsquality of niosomes from maltodextrin-based proniosomes, 2001, 18: 656-661.
  11. Akul Mehta, PharmaXChange_info - Articles – Niosomes
  12. Ruckmani K, Jayakar B and Ghosal SK, Drug Development andIndustrial Pharmacy, 26, 2000, pp. 217-222.
  13. Baillie AJ, Coombs GH and Dolan TF, Non-ionic surfactant vesicles, niosomes, as delivery system for the anti-leishmanial drug, sodium stribogluconate, J. Pharm. Pharmacol., 38, 1986, pp. 502-505
  14. Conacher M, Alexanderand J, Brewer JM, Conacher M, and Alexander J, Niosomes as Immunological Adjuvants. In “Synthetic Surfactant Vesicles” (Ed. I.F. Uchegbu) International Publishers Distributors Ltd. Singapore, 2000, pp. 185-205.
  15. Azmin MN, Florence AT, Handjani-Vila RM, Stuart JB, Vanlerberghe, G and Whittaker JS, J. Pharm. Pharmacol., 37, 1985, pp, 237.
  16. Gadhiya P, Shukla S, Modi D, Bharadia P, A Review- Niosomes in Targeted Drug Delivery, International Journal for Pharmaceutical Research Scholars, 2, 2012, pp. 60.
  17. Pawar SD, Pawar RG, Kodag PP, Waghmare AS, Niosome: An Unique Drug Delivery System, International Journal of Biology, Pharmacy and Allied Sciences,3, 2012, pp. 412.
  18. Namdeo, A., Jain, N.K., Niosomal delivery of 5-fluorouracil. J.Microencapsul, 1999; 16 (6): 731 –740.
  19. Bhaskaran S., Panigrahi L., Formulation and Evaluation of Niosomes using Different Nonionic Surfactant. Ind J Pharm Sci., 2002, 63: 1-6.
  20. Balasubramanian A., Formulation and In-Vivo Evaluation of Niosome Encapsulated Daunorubicin Hydrochloride. Drug Dev and Ind.Pharm, 2002, 3(2): 1181-84.
  21. Mayer L.D., Bally M.B., Hope M.J., Cullis P.R., Biochem Biophys. Acta, 1985, 816: 294-302.
  22. Raja Naresh R.A., Chandrashekhar G., Pillai G.K., Udupa N.,Antiinflammatory activity of Niosome encapsulated diclofenac sodium with Tween-85 in Arthitic rats. Ind.J. Pharmacol., 1994, 26: 46-48.
  23. Pal R, Pandey P, Waheed S, Thakur SK, Sharma V, Chanana A, Singh Rp. Transdermal Drug Delivery System (Tdds) As A Novel Tool For Drug Delivery.
  24. Dhiman J. Novel Drug Delivery System: Brief Review. Journal of  Drug Delivery and Therapeutics. 2023 Nov 15;13(11):188-96.
  25. Bhowmik D, Kumar KS. Recent Trends in Dermal and Transdermal  Drug Delivery Systems: Current and Future Prospects. The Pharma Innovation. 2013 Aug 1;2(6, Part A):1.
  26. Singh K, Walia MK, Agarwal G, Harikumar SL. Osmotic pump drug delivery system: a noval approach. Journal of Drug Delivery and Therapeutics. 2013 Sep 14;3(5):156-62.
  27. Pal R, Pandey P, Nogai L. The Advanced Approach in The Development of Targeted Drug Delivery (TDD) With Their BioMedical Applications: A Descriptive Review. International Neurourology Journal. 2023 Oct 7;27(4):40-58
  28. Debnath A, Kumar A. Structural and Functional significance of Niosome and Proniosome in Drug Delivery System. International Journal of Pharmacy and Engineering. 2015; 3: 621-637.
  29. Jindal K. Niosomes as a Potntial Carrier System: A Review. IJPCBS. 2015; 5:947-959.
  30. Kaur H, Dhiman S, Arora S. Niosomes: A novel drug delivery system. Int. J.Pharm. Sci. Rev. Res. 2012; 15: 113-120.
  31. Navya M. Niosomes As novel vesicular drug delivery system- A review. Asian Journal of Research in Biological and Pharmaceutical Sciences. 2014; 2: 62-68.
  32. Verma N. Niosomes and Its Application -A Review. IJRPLS. 2014; 2: 182 184.
  33. Sharma S. Span-60 Niosomal Oral Suspension of Flucanazole: Formulation and in-vitro evaluation. Asian journal of pharmaceutical research and health care. 2009; 1: 142-156.
  34. Sahin NO. Niosomes as carrier systems, in: Mozafari MR (ed.), Nanomaterials and nanosystems for Biomedical Applications, Springer, Dordrecht, The Netherlands. 2007, pp 67-82.
  35. Kreuter J. Influence of the surfactant properties on nanoparticle-mediated transport of drugs to the brain. J. Nanosci. Nanotech. 2004; 4: 484-488.
  36. Kreuter J, Shamenkov D, Petrov V, Ramge P, Cychutek K, Koch-Brandt C, Alyautdin R. Apolipoprotein-mediated transport of nanoparticle-bound drugs across the blood-brain barrier, J. Drug Target. 2002; 10: 317-325.
  37. Begley DJ. Delivery of therapeutic agents to the central nervous system: the problems and possibilities. Pharmacol. Therap. 2004; 104: 29-45.
  38. Rousselle C, Clair P, Lefacounnier J, Kaczorek M, Schermann JM, Temsaman JM. New advances in the transport of doxorubicin through the blood-brain barrier by a peptide vector-mediated strategy. Mol. Pharmacol. 2000; 57: 679-686.
  39. Suzuki K and Sokan K. The Application of Liposomes to Cosmetics. Cosmetic and Toiletries, 105,1990, 65-78.
  40. Brewer JM and Alexander JA. The adjuvant activity of non-ionic surfactant vesicles (niosomes) on the BALB/c humoral response to bovine serum albumin. Immunology. 75 (4), 1992, 570-575.
  41. Moser P. et al, Niosomes d’hémoglobine. I. Preparation, proprietes physicochimiques oxyphoriques,stabilite. Pharma. Acta.Helv, , 64 (7), 1989, 192-202.
  42. Jayaraman C.S., Ramachandran C. and Weiner N. Topical delivery of erythromycin from various formulations: an in vivo hairless mouse study. J. Pharm. Sci. 85 (10), 1996, 1082-1084.
  43. Moghassemi S, Hadjizadeh A. Nano-niosomes as nanoscale drug  delivery systems: an illustrated review. J Controlled Release. 2014;185:22–36. https://doi.org/10.1016/j.jconrel.2014.04.015
  44. Mahmoud K, Mohamed M, Amr I, Dina L. An overview on Niosomes: a drug nanocarrier. Drug Des Int Prop Int J. 2018;1(5):143–151. https://doi.org/10.32474/DDIPIJ.2018.01.000125
  45. Yamaguchi S, Kimura Z, Misono T, et al. Preparation and properties of nonionic vesicles prepared with polyglycerol fatty acid esters using the supercritical carbon dioxide reverse phase evaporation method. J Oleo Sci. 2016:65(3)201–206. https://doi.org/10.5650/jos.ess15217
  46. Yeo PL, Lim CL, Chye SM, Ling AK, Koh RY. Niosomes: a review of their structure, properties, methods of preparation, and medical applications. Asian Biomed. 2017;11(4):301–314.https://doi.org/10.1515/abm-2018-0002
  47. Ojeda E, Agirre M, Villate-Beitia I, et al. Elaboration and physicochemical characterization of niosome-based nioplexes for gene delivery purposes. In: Candiani G, ed. Non-Viral Gene Delivery Vectors. New York, NY: Humana Press; 2016:63–75.
  48. Bhavani G, Lakshmi P. Recent advances of non-ionic surfactant-based nano-vesicles (niosomes and proniosomes): a brief review of these in enhancing transdermal delivery of drug. Future J Pharm Sci. 2020;6(1):1–18.
  49. Khan R, Irchhaiya R. Niosomes: a potential tool for novel drug delivery.J Pharm Investig. 2016;46(3):195–204. https://doi.org/10.1007/s40005-016-0249-9
  50. Ag Seleci D, Seleci M, Walter J-G, Stahl F, Scheper T. Niosomes as nanoparticular drug carriers: fundamentals and recent applications. J Nanomater. 2016;2016:e7372306. https://doi.org/10.1155/2016/7372306
  51. Kamboj S, Saini V, Bala S. Formulation and characterization of drug loaded nonionic surfactant vesicles (niosomes) for oral bioavailability enhancement. Sci World J. 2014;2014:e959741. https://doi.org/10.1155/2014/959741
  52. Seyfoddin A, Sherwin T, V Patel D, et al. Ex vivo and in vivo evaluation of chitosan coated nanostructured lipid carriers for ocular delivery of acyclovir. Curr Drug Deliv. 2016;13(6):923–934.
  53. Manosroi A, et al. Characterization of vesicles prepared with various non-ionic surfactants mixed with cholesterol. Colloids Surf B. 2003;30(1–2):129–38.
  54. Duncan R, Florence A, Uchegbu I, Cociacinch F, 1997. Drug Polymer conjugates encapsulated within niosomes. International Patent Application PCT: GB97:00072.
  55. Gianasi E, Cociancich F, Uchegbu IF, Florence AT, Duncan R. Pharmaceutical and biological characterization of a doxorubicin-polymer conjugate (PK1) entrapped in sorbitan monostearate Span 60 niosomes. Int J Pharm 1997;148:139-48.
  56. Bhaskaran S, Lakshmi PK. Comparative evaluation of niosome formulations prepared by different techniques. Acta Pharm Sci 2009;51:27-32.
  57. Martin JF. Pharmaceutical manufacturing of liposomes. In: Tyle P, editor. Specialized drug delivery systems manufacturing and production technology. New York:Marcel Dekker; 1990. p. 267-314.
  58. Ahuja N, Saini V, Bishnoi VK, Garg A, Hisoria M, Sharma J. Formulation and evaluation of lansoprazole niosome. Rasayan J Chem 2008;1:561-3 [62].
  59. Gyanendra S, Harinath D, Shailendra KS, Shubhini AS. Niosomal delivery of isoniazide development and characterization. Trop J Pharm Res 2011;10:203-10.
  60. Michael W, Gerhard W, Heinrich H, Klaus D. Liposome preparation by single-pass process. US patent 20100316696 A1; 2010.
  61. Karim KM, Mandal AS, Biswas N, Guha A, Chatterjee S, Behera M. Niosome: a future of targeted drug delivery systems. J Adv Pharm Technol Res 2010;1:374-80
  62. Frank LS, Huang L. Large scale production of DC Chol cationic liposomes by micro fluidization. Int J Pharm 1996;144:131-9.
  63. Sathali AH, Rajalakshmi G. Evaluation of transdermal targeted niosomal drug delivery of terbinafine hydrochloride. Int J Pharm Technol Res 2010;2:2081-9.
  64. Blazek-Walsh AI, Rhodes DG. SEM imaging predicts quality of niosomes from maltodextrin-based proniosomes. Pharm Res 2001;18:656-61.
  65. Farkas E, Schubert R, Zelko R. Effect of beta sitosterol on the characteristics of vesicular gels containing chlorhexidine. Int J Pharm 2004;278:63-70.
  66. Marianecci C, Rinaldi F, Mastriota M, Pieretti S, Trapasso E, Paolino D, et al. J Control Release 2012;164:17. 67. Lakshmi PK, Devi GS, Bhaskaran S, Sacchidanand S. Indian J Dermatol Venereol Leprol 2007;73:157.
  67. Marianecci C, Carafa M, Di Marzio L, Rinaldi F, Di Meo C, Matricardi P, et al. J Pharm Pharm Sci 2011;14:336. 69. Kaur P, Aggarwal D, Singh H, Kakkar S. Graefes Arch Clin Exp Ophthalmol 2010;248:1467
  68. Alsaadi M, Italia JL, Mullen AB, Ravi Kumar MNV, Candlish AA, Williams RAM, et al. J Control Release 2012;160:685. 71.  El-Ridy MS, Abdelbary A, Nasr EA, Khalil RM, Mostafa DM, El-Batal AI, et al. Drug Dev Ind Pharm 2011;37:1110.
  69. Xu Y, Li Q. Tacrolimus ophthalmic preparation for corneal transplantation and production method thereof by; 2013 [CN 103142468 A 20130612].
  70. Alhaique F, Carafa M, Fresta M, Marianecci C, Paolino D. Niosomes, freeze-dried powder thereof and their use in treatment of respiratory disorders by; 2013[IT 1397274 B1 20130104].
  71. Ghulam Nabi Qazi, Farhan Jalees Ahmad, Mohd Samim, Deborah Cooper, Marnickavasagar V, Rajendran M. Collagen nanostructures; 2013 [WO 2013015674A1 20130131].
  72. Deng Y, Yang Q, Zhang X. Metformin-containing niosome-like drug delivery system and its application by; 2012 [CN 102755292 A 20121031]. 76. Anderson DE. Thermostable lyophilized immunogenic compositions of an inactivated viral antigen with a non-ionic surfactant vesicle for treating viral infections; 2013 [WO 2013104995 A2 20130718].
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Reference

  1. Sankar V, Ruckmani K, Jailan S, Ganesan KS, Sharavanan S. Niosome drug delivery system: advances and medical applications an overview. Pharmacol Online.,2009;926-32.
  2. Uchegbu IF, Vyas SP. Non-ionic surfactant based vesicles (niosomes) in drug delivery. Int J Pharm., 1998; 172: 33-70.
  3. Uchegbu IF, Florence AT. Non-ionic surfactant vesicles (niosomes): physical and pharmaceutical chemistry. Adv Colloid Interface Sci., 1995; 58: 1–55.
  4. Bouwstra JA, Van HD, Hofland HE. Preparation and characterization of non ionic surfactant vesicles. Colloids Surf A Physicochem Eng Asp., 1997; 80: 123-4.
  5. Rangasamy M, Ayyasamy B, Raju S, Develly SG, Shaik S. Formulation and in-vitro evaluation of noisome encapsulated acyclovir. J Pharm Res., 2008; 1: 163-6.
  6. Ijeoma F., Uchegbu., Suresh P., Vyas., Non-ionic surfactant based vesicles (niosomes) in drug delivery. Int. J. Pharm., 1998; 172: 33–70.
  7. Malhotra M., Jain N.K., Niosomes as Drug Carriers. Indian Drugs, 1994; 31(3): 81-866.
  8. Alsarra A., Bosela A,, Ahmed S.M,, Mahrous G.M., Proniosomes as a drug carrier for transdermal delivery of ketorolac. Eur. J. Pharm. and Biopharm,2004; 2(1): 1-6.
  9. Hu C., Rhodes D.G., Proniosomes: a novel drug carrier preparation. Int. J. Pharm. 1999, 185: 23-35.
  10. Blazek-Walsh A.I., and Rhodes D.G., Pharm. Res. SEM imaging predictsquality of niosomes from maltodextrin-based proniosomes, 2001, 18: 656-661.
  11. Akul Mehta, PharmaXChange_info - Articles – Niosomes
  12. Ruckmani K, Jayakar B and Ghosal SK, Drug Development andIndustrial Pharmacy, 26, 2000, pp. 217-222.
  13. Baillie AJ, Coombs GH and Dolan TF, Non-ionic surfactant vesicles, niosomes, as delivery system for the anti-leishmanial drug, sodium stribogluconate, J. Pharm. Pharmacol., 38, 1986, pp. 502-505
  14. Conacher M, Alexanderand J, Brewer JM, Conacher M, and Alexander J, Niosomes as Immunological Adjuvants. In “Synthetic Surfactant Vesicles” (Ed. I.F. Uchegbu) International Publishers Distributors Ltd. Singapore, 2000, pp. 185-205.
  15. Azmin MN, Florence AT, Handjani-Vila RM, Stuart JB, Vanlerberghe, G and Whittaker JS, J. Pharm. Pharmacol., 37, 1985, pp, 237.
  16. Gadhiya P, Shukla S, Modi D, Bharadia P, A Review- Niosomes in Targeted Drug Delivery, International Journal for Pharmaceutical Research Scholars, 2, 2012, pp. 60.
  17. Pawar SD, Pawar RG, Kodag PP, Waghmare AS, Niosome: An Unique Drug Delivery System, International Journal of Biology, Pharmacy and Allied Sciences,3, 2012, pp. 412.
  18. Namdeo, A., Jain, N.K., Niosomal delivery of 5-fluorouracil. J.Microencapsul, 1999; 16 (6): 731 –740.
  19. Bhaskaran S., Panigrahi L., Formulation and Evaluation of Niosomes using Different Nonionic Surfactant. Ind J Pharm Sci., 2002, 63: 1-6.
  20. Balasubramanian A., Formulation and In-Vivo Evaluation of Niosome Encapsulated Daunorubicin Hydrochloride. Drug Dev and Ind.Pharm, 2002, 3(2): 1181-84.
  21. Mayer L.D., Bally M.B., Hope M.J., Cullis P.R., Biochem Biophys. Acta, 1985, 816: 294-302.
  22. Raja Naresh R.A., Chandrashekhar G., Pillai G.K., Udupa N.,Antiinflammatory activity of Niosome encapsulated diclofenac sodium with Tween-85 in Arthitic rats. Ind.J. Pharmacol., 1994, 26: 46-48.
  23. Pal R, Pandey P, Waheed S, Thakur SK, Sharma V, Chanana A, Singh Rp. Transdermal Drug Delivery System (Tdds) As A Novel Tool For Drug Delivery.
  24. Dhiman J. Novel Drug Delivery System: Brief Review. Journal of  Drug Delivery and Therapeutics. 2023 Nov 15;13(11):188-96.
  25. Bhowmik D, Kumar KS. Recent Trends in Dermal and Transdermal  Drug Delivery Systems: Current and Future Prospects. The Pharma Innovation. 2013 Aug 1;2(6, Part A):1.
  26. Singh K, Walia MK, Agarwal G, Harikumar SL. Osmotic pump drug delivery system: a noval approach. Journal of Drug Delivery and Therapeutics. 2013 Sep 14;3(5):156-62.
  27. Pal R, Pandey P, Nogai L. The Advanced Approach in The Development of Targeted Drug Delivery (TDD) With Their BioMedical Applications: A Descriptive Review. International Neurourology Journal. 2023 Oct 7;27(4):40-58
  28. Debnath A, Kumar A. Structural and Functional significance of Niosome and Proniosome in Drug Delivery System. International Journal of Pharmacy and Engineering. 2015; 3: 621-637.
  29. Jindal K. Niosomes as a Potntial Carrier System: A Review. IJPCBS. 2015; 5:947-959.
  30. Kaur H, Dhiman S, Arora S. Niosomes: A novel drug delivery system. Int. J.Pharm. Sci. Rev. Res. 2012; 15: 113-120.
  31. Navya M. Niosomes As novel vesicular drug delivery system- A review. Asian Journal of Research in Biological and Pharmaceutical Sciences. 2014; 2: 62-68.
  32. Verma N. Niosomes and Its Application -A Review. IJRPLS. 2014; 2: 182 184.
  33. Sharma S. Span-60 Niosomal Oral Suspension of Flucanazole: Formulation and in-vitro evaluation. Asian journal of pharmaceutical research and health care. 2009; 1: 142-156.
  34. Sahin NO. Niosomes as carrier systems, in: Mozafari MR (ed.), Nanomaterials and nanosystems for Biomedical Applications, Springer, Dordrecht, The Netherlands. 2007, pp 67-82.
  35. Kreuter J. Influence of the surfactant properties on nanoparticle-mediated transport of drugs to the brain. J. Nanosci. Nanotech. 2004; 4: 484-488.
  36. Kreuter J, Shamenkov D, Petrov V, Ramge P, Cychutek K, Koch-Brandt C, Alyautdin R. Apolipoprotein-mediated transport of nanoparticle-bound drugs across the blood-brain barrier, J. Drug Target. 2002; 10: 317-325.
  37. Begley DJ. Delivery of therapeutic agents to the central nervous system: the problems and possibilities. Pharmacol. Therap. 2004; 104: 29-45.
  38. Rousselle C, Clair P, Lefacounnier J, Kaczorek M, Schermann JM, Temsaman JM. New advances in the transport of doxorubicin through the blood-brain barrier by a peptide vector-mediated strategy. Mol. Pharmacol. 2000; 57: 679-686.
  39. Suzuki K and Sokan K. The Application of Liposomes to Cosmetics. Cosmetic and Toiletries, 105,1990, 65-78.
  40. Brewer JM and Alexander JA. The adjuvant activity of non-ionic surfactant vesicles (niosomes) on the BALB/c humoral response to bovine serum albumin. Immunology. 75 (4), 1992, 570-575.
  41. Moser P. et al, Niosomes d’hémoglobine. I. Preparation, proprietes physicochimiques oxyphoriques,stabilite. Pharma. Acta.Helv, , 64 (7), 1989, 192-202.
  42. Jayaraman C.S., Ramachandran C. and Weiner N. Topical delivery of erythromycin from various formulations: an in vivo hairless mouse study. J. Pharm. Sci. 85 (10), 1996, 1082-1084.
  43. Moghassemi S, Hadjizadeh A. Nano-niosomes as nanoscale drug  delivery systems: an illustrated review. J Controlled Release. 2014;185:22–36. https://doi.org/10.1016/j.jconrel.2014.04.015
  44. Mahmoud K, Mohamed M, Amr I, Dina L. An overview on Niosomes: a drug nanocarrier. Drug Des Int Prop Int J. 2018;1(5):143–151. https://doi.org/10.32474/DDIPIJ.2018.01.000125
  45. Yamaguchi S, Kimura Z, Misono T, et al. Preparation and properties of nonionic vesicles prepared with polyglycerol fatty acid esters using the supercritical carbon dioxide reverse phase evaporation method. J Oleo Sci. 2016:65(3)201–206. https://doi.org/10.5650/jos.ess15217
  46. Yeo PL, Lim CL, Chye SM, Ling AK, Koh RY. Niosomes: a review of their structure, properties, methods of preparation, and medical applications. Asian Biomed. 2017;11(4):301–314.https://doi.org/10.1515/abm-2018-0002
  47. Ojeda E, Agirre M, Villate-Beitia I, et al. Elaboration and physicochemical characterization of niosome-based nioplexes for gene delivery purposes. In: Candiani G, ed. Non-Viral Gene Delivery Vectors. New York, NY: Humana Press; 2016:63–75.
  48. Bhavani G, Lakshmi P. Recent advances of non-ionic surfactant-based nano-vesicles (niosomes and proniosomes): a brief review of these in enhancing transdermal delivery of drug. Future J Pharm Sci. 2020;6(1):1–18.
  49. Khan R, Irchhaiya R. Niosomes: a potential tool for novel drug delivery.J Pharm Investig. 2016;46(3):195–204. https://doi.org/10.1007/s40005-016-0249-9
  50. Ag Seleci D, Seleci M, Walter J-G, Stahl F, Scheper T. Niosomes as nanoparticular drug carriers: fundamentals and recent applications. J Nanomater. 2016;2016:e7372306. https://doi.org/10.1155/2016/7372306
  51. Kamboj S, Saini V, Bala S. Formulation and characterization of drug loaded nonionic surfactant vesicles (niosomes) for oral bioavailability enhancement. Sci World J. 2014;2014:e959741. https://doi.org/10.1155/2014/959741
  52. Seyfoddin A, Sherwin T, V Patel D, et al. Ex vivo and in vivo evaluation of chitosan coated nanostructured lipid carriers for ocular delivery of acyclovir. Curr Drug Deliv. 2016;13(6):923–934.
  53. Manosroi A, et al. Characterization of vesicles prepared with various non-ionic surfactants mixed with cholesterol. Colloids Surf B. 2003;30(1–2):129–38.
  54. Duncan R, Florence A, Uchegbu I, Cociacinch F, 1997. Drug Polymer conjugates encapsulated within niosomes. International Patent Application PCT: GB97:00072.
  55. Gianasi E, Cociancich F, Uchegbu IF, Florence AT, Duncan R. Pharmaceutical and biological characterization of a doxorubicin-polymer conjugate (PK1) entrapped in sorbitan monostearate Span 60 niosomes. Int J Pharm 1997;148:139-48.
  56. Bhaskaran S, Lakshmi PK. Comparative evaluation of niosome formulations prepared by different techniques. Acta Pharm Sci 2009;51:27-32.
  57. Martin JF. Pharmaceutical manufacturing of liposomes. In: Tyle P, editor. Specialized drug delivery systems manufacturing and production technology. New York:Marcel Dekker; 1990. p. 267-314.
  58. Ahuja N, Saini V, Bishnoi VK, Garg A, Hisoria M, Sharma J. Formulation and evaluation of lansoprazole niosome. Rasayan J Chem 2008;1:561-3 [62].
  59. Gyanendra S, Harinath D, Shailendra KS, Shubhini AS. Niosomal delivery of isoniazide development and characterization. Trop J Pharm Res 2011;10:203-10.
  60. Michael W, Gerhard W, Heinrich H, Klaus D. Liposome preparation by single-pass process. US patent 20100316696 A1; 2010.
  61. Karim KM, Mandal AS, Biswas N, Guha A, Chatterjee S, Behera M. Niosome: a future of targeted drug delivery systems. J Adv Pharm Technol Res 2010;1:374-80
  62. Frank LS, Huang L. Large scale production of DC Chol cationic liposomes by micro fluidization. Int J Pharm 1996;144:131-9.
  63. Sathali AH, Rajalakshmi G. Evaluation of transdermal targeted niosomal drug delivery of terbinafine hydrochloride. Int J Pharm Technol Res 2010;2:2081-9.
  64. Blazek-Walsh AI, Rhodes DG. SEM imaging predicts quality of niosomes from maltodextrin-based proniosomes. Pharm Res 2001;18:656-61.
  65. Farkas E, Schubert R, Zelko R. Effect of beta sitosterol on the characteristics of vesicular gels containing chlorhexidine. Int J Pharm 2004;278:63-70.
  66. Marianecci C, Rinaldi F, Mastriota M, Pieretti S, Trapasso E, Paolino D, et al. J Control Release 2012;164:17. 67. Lakshmi PK, Devi GS, Bhaskaran S, Sacchidanand S. Indian J Dermatol Venereol Leprol 2007;73:157.
  67. Marianecci C, Carafa M, Di Marzio L, Rinaldi F, Di Meo C, Matricardi P, et al. J Pharm Pharm Sci 2011;14:336. 69. Kaur P, Aggarwal D, Singh H, Kakkar S. Graefes Arch Clin Exp Ophthalmol 2010;248:1467
  68. Alsaadi M, Italia JL, Mullen AB, Ravi Kumar MNV, Candlish AA, Williams RAM, et al. J Control Release 2012;160:685. 71.  El-Ridy MS, Abdelbary A, Nasr EA, Khalil RM, Mostafa DM, El-Batal AI, et al. Drug Dev Ind Pharm 2011;37:1110.
  69. Xu Y, Li Q. Tacrolimus ophthalmic preparation for corneal transplantation and production method thereof by; 2013 [CN 103142468 A 20130612].
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Shivram jadhav
Corresponding author

Department of Pharmaceutics, Yashwantrao Bhonsale College of Pharmacy, Sawantwadi, Maharashtra India

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Tushar Rukari
Co-author

Department of Pharmaceutics, Yashwantrao Bhonsale College of Pharmacy, Sawantwadi, Maharashtra India

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Dr. Vijay Jagtap
Co-author

Department of Pharmaceutics, Yashwantrao Bhonsale College of Pharmacy, Sawantwadi, Maharashtra India

Shivram Jadhav*, Tushar Rukari, Dr. Vijay Jagtap, Niosomes- The Swiss Army Knife of Drug Delivery System: A Comprehensive Review, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 1, 1489-1503. https://doi.org/10.5281/zenodo.14688777

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