niosomes: a novel drug delivery systemniosomes: a novel drug delivery system *jessy shaji1 and...

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Jessy et al. World Journal of Pharmaceutical Research

NIOSOMES: A NOVEL DRUG DELIVERY SYSTEM

*Jessy Shaji1 and Akshay Shah

1

1Department of Pharmaceutics, Prin. K M Kundnani College of Pharmacy 23, Jote Joy Bldg,

Rambhau Salgaonkar marg, Cuffe Parade, Colaba, Mumbai 400005, India.

ABSTRACT

Vesicular systems are novel means of delivering drug in a controlled

manner to enhance bioavailability and to get therapeutic effect over a

long period of time. Niosomes are one such hydrated vesicular system

containing non ionic surfactants along with cholesterol or other lipids

delivering drug to targeted site which are non toxic, requiring less

production cost, stable over a longer period of time in different

conditions, hence overcomes drawbacks of liposomes. Present review

describes history, all factors affecting niosome formulations,

manufacturing conditions, characterization, stability, administration

routes and also their comparison with liposome. This review also gives

relevant information regarding various applications of niosomes in

gene delivery, vaccine delivery, anticancer drug delivery, etc.

KEYWORDS: Niosomes, Encapsulation, Surfactants, Vesicles.

INTRODUCTION

Vesicular systems are novel means of delivering drug in a controlled

manner to enhance bioavailability and to get therapeutic effect over a longer period of time.

Vesicular systems are lamellar structures made up of amphiphilic molecules surrounded by

an aqueous compartment.[1–4]

Vesicular systems are useful for the delivery of both

hydrophilic and hydrophobic drugs which are encapsulated into the interior hydrophilic

compartment and outer lipid layer respectively. Vesicular systems are classified according to

their principle components used in preparation as shown in Table 1.

Liposome can encapsulate various types of drugs in controlled or sustained manner to

targeted site and are more advantageous over other drug delivery systems, but their high

World Journal of Pharmaceutical Research SJIF Impact Factor 5.990

Volume 4, Issue 6, 853-876. Review Article ISSN 2277– 7105

Article Received on

29 March 2015,

Revised on 22 April 2015,

Accepted on 13 May 2015

*Correspondence for

Author

Dr. Jessy Shaji

Department of

Pharmaceutics, Prin. K M

Kundnani College of

Pharmacy23, Jote Joy

Bldg, Rambhau

Salgaonkar marg, Cuffe

Parade, Colaba, Mumbai

400005, India.

http://www.wjpr.net/


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formulation cost and limited shelf life are key factors leading to the need of developing such

vesicular systems which can overcome drawbacks of liposome. Niosomes are such bilayer

system containing nonionic surfactants and cholesterol. They have longer shelf life, stability

and ability to deliver drug at target site in a controlled or sustained manner which enhances

bioavailability.[5–11]

Nonionic surfactants are used due to their ability to enhance solubility, and are used to

increase bioavailability of poorly water soluble drugs. Nonionic surfactant increases both

permeability and fluidity of biological membrane so drugs like podophylotoxin, etoposide,

and methotrexate show enhanced bioavailability by transdermal route via niosomes.[12]

Table 1: Different vesicular systems and their principal components.

Sr.no Vesicular systems Principal components

1 Liposomes Phospholipids (natural or synthetic)

2 Niosomes Nonionic surfactants+lipids

3 Ethosomes Phospholipids+ethanol

4 Transferosomes Phospholipids+single chain surfactants

5 Bilosomes Phospholipids+nonionoic surfactant+bile salts

HISTORY OF NIOSOMES

Niosomes were first introduced as a feature of cosmetic industry. Nonionic surfactants are

preferred due their less irritation power which decreases in the order of

cationic>anionic>ampholytic>non-ionic surfactants. Nonionic surfactants are comprised of

polar and non-polar segments as depicted in Fig. 1, possessing high interfacial activity which

upon hydration form bilayer in and hence entrap both hydrophilic and hydrophobic drugs.

The first report of non-ionic surfactant vesicles came from the cosmetic applications devised

by L'Oreal.[13]

ADVANTAGES OF NIOSOMES

1. Entrap solute in a manner analogous to liposomes.

2. Osmotically active & stable , increase the stability of entrapped drug .

3.Handling & storage of surfactants require no special conditions.

4.Accommodate drug molecules with a wide range of solubility.

5.Exhibit flexibility in their structural characteristics (composition fluidity & size) & can be

designed according to the desired situation.

6.Improve oral bioavailability of poorly absorbed drugs & can also enchance skin penetration

of drugs.



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7. Can be made to reach the site of action by oral, parenteral as well as topical routes.

8. Niosomal surfactants are biodegradable, biocompatible & non – immunogenic & non toxic

9. Niosomes improve the therapeutic performance of the drug molecules by delayed

clearance from the circulation, protecting the drug form biological environment & restricting

the effects to target cells.

10.They can prolong the circulation of the entrapped drugs.

DISADVANTAGES OF NIOSOMES

In rare cases, non ionic surfactants interacts with other components of the system rendering

the formulation homogenous or form precipitates.

STRUCTURE OF NIOSOMES

Niosomes are a novel drug delivery system, in which the medication is encapsulated in a

vesicle composed of a bilayer of non-ionic surface active agents. These are very small in size

and lies in the nanometric scale. Niosomes are microscopic lamellar structures, which are

formed on admixture of non-ionic surfactant of the alkyl or dialkyl polyglycerol ether class

and cholesterol with subsequent hydration in aqueous media. Niosomes may be unilamellar

or multilamellar. The hydrophilic ends are exposed on the outside and inside of the vesicle,

while the hydrophobic chains face each other within the bilayer. Hence, the vesicle holds

hydrophilic drugs within the spaces enclosed in the vesicle, while hydrophobic drugs are

embedded within the bilayer itself. Fig. 1

Fig 1. Niosome structure.



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DEFORMABLE NIOSOMES:

Fig 2. Mechanism of skin permeation of deformable niosome adapted from reference

(Kumar G.P. & Rao, P.R., (2012). Ultra deformable niosomes for improved transdermal drug

delivery: The future scenario Asian Journal of Pharmaceutical Sciences, Vol. 7, No. 2, pp.

96-109.)

Elastic niosomes are prepared from nonionic surfactants, ethanol and water. They show

superior activity to conventional niosomes due to their capability to increase penetration

efficiency of a compound through intact skin by passing through pores in the stratum

corneum, which are smaller than the vesicles (figure). The flexibility of their structure allows

them to pass through pores that are less than one-tenth the size of these vesicles (Cevc, 1996;

Cevc et al., 1996).

TYPES OF NIOSOMES

The various types of niosomes are described below;

i) Multi lamellar vesicles (MLV),

ii) Large unilamellar vesicles (LUV),

iii) Small unilamellar vesicles (SUV).

The niosomes are classified as a function of the number of bilayer (e.g. MLV, SUV) or as a

function of size. (e.g.LUV, SUV) or as a function of the method of preparation (e.g.REV,

DRV).

i) Multi lamellar vesicles (MLV)

It consists of a number of bilayer surrounding the aqueous lipid compartment separately. The

approximate size of these vesicles is 0.5-10 μm diameter. Multilamellar vesicles are the most



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widely used niosomes. It is simple to make and are mechanically stable upon storage for long

periods. These vesicles are highly suited as drug carrier for lipophilic compounds.

ii) Large unilamellar vesicles (LUV)

Niosomes of this type have a high aqueous/lipid compartment ratio, so that larger volumes of

bio-active materials can be entrapped with economical use of membrane lipids.

iii) Small unilamellar vesicles (SUV)

These small unilamellar vesicles are mostly prepared from multilamellar vesicles by

sonication method, French press extrusion electrostatic stabilization is the inclusion of dicetyl

phosphate in 5(6)-carboxyfluorescein (CF) loaded Span 60 based niosomes.

METHOD OF PREPARATION

CHOLESTEROL + NON IONIC SURFACTANT

DISSOLVE IN ORGANIC SOLVENT

SOLUTION IN ORGANIC SOLVENT

DRYING

THIN FILM

DISPERSION (HYDRATION)

NOISOME DISPERSION

Fig 3. Shows flowchart of method of preparation of niosomes

A. Ether injection method

In this method, the lipids and drug are dissolved in diethyl ether and injected slowly into an

aqueous phase, which is heated above the boiling point of the organic solvent. This produces

large unilamellar vesicles, which are further subjected to size reduction. (Bhaskaran and

Lakshmi prepared salbutamol niosomes by ether injection with an entrapment efficiency of

67.7% ).[52]



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B. Hand shaking method (Thin film hydration technique)

The mixture of vesicles forming ingredients like surfactant and cholesterol are dissolved in a

volatile organic solvent (diethyl ether, chloroform or methanol) in a round bottom flask. The

organic solvent is removed at room temperature (20°C) using rotary evaporator leaving a thin

layer of solid mixture deposited on the wall of the flask. The dried surfactant film can be

rehydrated with aqueous phase at 0-60°C with gentle agitation. This process forms typical

multilamellar niosomes.

Fig 4 : Hand Shaking Method Of Niosomes Preparations

C. Sonication

A typical method of production of the vesicles is by sonication of solution as described by

Cable. In this method an aliquot of drug solution in buffer is added to the

surfactant/cholesterol mixture in a 10-ml glass vial. The mixture is probe sonicated at 60°C

for 3 minutes using a sonicator with a titanium probe to yield niosomes.

A) Bath sonicator B) Probe sonicator

Fig 5 : Sonication technique



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D. Micro fluidization

Micro fluidization is the process where a solution of surfactants and drug is pumped under

pressure from a reservoir through an interaction chamber packed in ice at a rate of 100

ml/min. From the interaction chamber, the solution is passed through a cooling loop to

remove the heat produced during micro fluidization and returned to the reservoir for

recirculation or allowed to exit the system. The process is repeated until a vesicle of the

desired size is produced.[54]

E. Trans membrane pH gradient method

Equal proportions of surfactant and cholesterol are dissolved in chloroform and evaporated

under reduced pressure to produce a thin lipid film on the wall of a round bottomed flask. The

film is hydrated with a solution of an acidic compound, generally citric acid by vortex

mixing. The resulting product is subjected to freeze thaw cycles after which an aqueous

solution of drug is added and the mixture vortexed. The pH of the sample is then raised to 7–

7.2 using disodium hydrogen phosphate solution.[53]

F. Reverse Phase Evaporation Technique (REV)

The surfactants are dissolved in a mixture of ether and chloroform to which an aqueous phase

containing the drug is added. The resulting two-phase system is then homogenized and the

organic phase evaporated under reduced pressure to form niosomes dispersed in the aqueous

Phase.[53]

Fig 6: Reverse Phase Evaporation Technique



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G. Formation of niosomes from proniosomes

Fig 7: Niosome formulations from proniosomes

Another method of producing niosomes is to coat a water soluble carrier such as sorbitol with

surfactant. The result of the coating process is a dry formulation in which each water-soluble

particle is covered with a thin film of dry surfactant. This preparation is termed

“Proniosomes”. The niosomes are recognized by the addition of aqueous phase at T > Tm and

brief agitation as shown in figure 7.

T = Temperature

Tm = mean phase transition temperature.

Blazek-Walsh A.I. et al. have reported the formulation of niosomes from maltodextrin based

proniosomes. This provides rapid reconstitution of niosomes with minimal residual carrier.

Slurry of maltodextrin and surfactant was dried to form a free flowing powder, which could

be rehydrated by addition of warm water.[60]

Post-Preparation Processes

The main post-preparation processes in the manufacture of niosomes are downsizing and

separation of unentrapped material. After preparation, size reduction of niosomes is achieved

using one of the methods given below:

1. Probe sonication results in the production of niosomes in the 100–140 nm size range.

2. Extrusion through filters of defined pore sizes.

3. Combination of sonication and filtration has also been used to obtain niosomes in the

200nm size range (e.g. doxorubicin niosomes).

4. Microfluidization yields niosomes in nano range



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5. High-pressure homogenisation also yields vesicles below 100nm in diameter.

As in most cases 100% of the bioactive agent cannot be encapsulated in the niosomal

vesicles, the unentrapped bioactive agent should be separated from the entrapped ones

This provides an advantage since this drug delivery system gives an initial burst to initiate

therapy followed by a sustained maintenance dose.

Most commonly used methods for separating unentrapped material from niosomes are

as follows.

• Dialysis;

• Gel filtration (e.g. Sephadex G50);

• Centrifugation (e.g. 7000 rpm for 30 min for the niosomes prepared by handshaking

and ether injection methods);

• Ultracentrifugation (150000 rpm for 1.5 h).

FACTORS AFFECTING THE FORMATION OF NIOSOMES

1. Type of Surfactants

The type of surfactants influences encapsulation efficiency, toxicity, and stability of

niosomes. The first niosomes were formulated using cholesterol and single-chain surfactants

such as alkyl oxyethylenes. The alkyl group chain length is usually from C12–C18. The

hydrophyle- lipophyle balance (HLB) is a good indicator of the vesicle forming ability of any

surfactant .It is reported that the sorbitan monostearate (Span) surfactants with HLB values

between 4 and 8 were found to be compatible with vesicle formation.Polyglycerol monoalkyl

ethers and polyoxylate analogues are the most widely used single-chain surfactants.However,

it must be noted that they possess less encapsulation efficiency in the presence of cholesterol.

Etheric surfactants have also been used to form niosomes. These types of surfactants are

composed of single-chain, monoalkyl or dialkyl chains. The latest ones are similar to

phospholipids and possess higher encapsulation efficiency. Ester type amphyphilic

surfactants are also used for niosome formulation. They are degraded by estherases,

triglycerides and fatty acids. Although these types of surfactants are less stable than ether

types, they possess less toxicity. Furthermore, glucosides of myrstyl, cetyl and stearyl

alcohols form niosomes.[14-33]



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Table 2 :HLB value of surfactant and their impact on niosome formation.

HLB value Impact on formulation

14–16 Does not produce niosomes

8.6 Increase entrapment efficiency of niosomes

1.7 to 8.6 Decreases entrapment efficiency

>6 Needs to add cholesterol in the formation of bilayer vesicle

Lower value Needs to add cholesterol to increase stability

Fig 8: The effect of the surfactant on the properties of niosome dispersion

2. Surfactant/Lipid and Surfactant/Water Ratios

Other important parameters are the level of surfactant/lipid and the surfactant/water ratio. The

surfactant/lipid ratio is generally 10–30 mM (1–2.5% w/w). If the level of surfactant/lipid is

too high, increasing the surfactant/lipid level increases the total amount of drug encapsulated.

Change in the surfactant/water ratio during the hydration process may affect the system’s

microstructure and thus, the system’s properties.[50]

3. Cholesterol

Steroids are important components of cell membranes and their presence in membranes

brings about significant changes with regard to bilayer stability, fluidity and

permeability.[46][48][49]

Cholesterol, a natural steroid, is the most commonly used membrane

additive and can be incorporated into bilayers structure. Cholesterol by itself, however, does

not form bilayer vesicles. It is usually included in a 1:1 molar ratio in most formulations to

prevent vesicle aggregation by the inclusion of molecules that stabilize the system against the

formation of aggregates by repulsive steric or electrostatic effects. It leads to transition from

the gel state to liquid phase in niosome systems. As a result, niosomes become less leaky.



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Fig 9: Structural interaction of Span 60 and cholesterol.[49]

4. Other Additives

As is the case with liposomes, charged phospholipids such as dicethylphosphate (DCP) and

stearyl amine (SA) have been used to produce charge in niosome formulations. The former

molecule provides negative charge to vesicles whereas the later one is used in the preparation

of positively charged (cationic) niosomes.

5. Nature of the Drug

One of the overlooked factors is the influence of the nature of the encapsulated drug on

vesicle formation (Table 3). The encapsulation of the amphipathic drug doxorubicin has been

shown to alter the electrophoretic mobility of hexadecyl diglycerol ether (C16G2) niosomes

in a pH dependent manner, indicating that the amphipathic drug is incorporated in the vesicle

membrane.[51]



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Fig 10: The effect of the nature of the encapsulated drug on the properties of the

niosome dispersion.

6) Temperature of Hydration

Hydration temperature influences the shape and size of the niosome. For ideal condition it

should be above the gel to liquid phase transition temperature of the system .Temperature

change of niosomal system affects assembly of surfactants into vesicles and also induces

vesicle shape transformation.[43]

7) Critical packing parameter (CPP)

On the basis of the CPP of a surfactant, the type of vesicle which it will form can be predicted

as shown in fig 11. The method of calculating CPP from the volume of the hydrophobic

group, area of the hydrophilic head group and length of the lipophilic alkyl chain of the

surfactant is shown in fig 11.

If CPP≤0.05 micelles may form, if CPP=0.5–1.0 spherical vesicles may form and if CPP≥1.0

inverted micelles formation will occur.[43]



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Fig 11: Critical packing parameter (CPP) of an amphiphile, where v is the hydrophobic

group volume, lc the critical hydrophobic group length and a0 the area of the

hydrophilic head group

CHARACTERIZATION OF NIOSOMES

1. Size, shape and charge

The characterization methods of niosomes size, shape and charge are as shown in Table 3.

Table 3

2. Bilayer Formation

Assembly of non-ionic surfactants to form a bilayer vesicle is characterized by an X cross

formation under light polarization microscopy.



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3. Number of Lamellae

This is determined by using nuclear magnetic resonance (NMR) spectroscopy, small angle X-

ray scattering and electron microscopy.

4. Membrane Rigidity

Membrane rigidity can be measured by means of mobility of fluorescence probe as a

function of temperature.

5. Entrapment Efficiency

After preparing niosomal dispersion, unentrapped drug is separated by dialysis,

centrifugation, or gel filtration as described above and the drug remained entrapped in

niosomes is determined by complete vesicle disruption using 50% n-propanol or 0.1% Triton

X-100 and analyzing the resultant solution by appropriate drug assay method.

Entrapment efficiency = (Amount entrapped / total amount) x 100.[62]

6. Niosomal drug loading and encapsulation efficiency

To determine drug loading and encapsulation efficiency, the niosomal aqueous suspension

was ultracentrifuged, supernatant was removed and sediment was washed twice with distilled

water in order to remove the adsorbed drug.

The niosomal recovery was calculated as:

Amount of niosomes recovered

Niosome recovery (%) = -----------------------------------------------X 100

Amount of polymer + Drug + Excipient

The entrapment efficiency (EE) was then calculated using formula:

Amount of drug in niosomes

Entrapment efficiency (%)= --------------------------------------------X 100

Amount of Drug used

The drug loading was calculated as:

Amount of drug in niosomes

Drug loading (%) = -----------------------------------------------X 100

Amount of niosomes recovered

Separation of Unentrapped Drug

The removal of unentrapped solute from the vesicles can be accomplished by various

techniques, which include.



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1. Dialysis

The aqueous niosomal dispersion is dialyzed in dialysis tubing against phosphate buffer or

normal saline or glucose solution.

2. Gel Filtration

The unentrapped drug is removed by gel filtration of niosomal dispersion through a

Sephadex-G-50 column and elution with phosphate buffered saline or normal saline.

3. Centrifugation

The niosomal suspension is centrifuged and the supernatant is separated. The pellet is washed

and then resuspended to obtain a niosomal suspension free from unentrapped drug.

STABILITY OF NIOSOMES

Vesicles are stabilized based upon formation of 4 different forces.

1. Van der Waals forces among surfactant molecules.

2. Repulsive forces emerging from the electrostatic interactions among charged groups of

surfactant molecules.

3. Entropic repulsive forces of the head groups of surfactants.

4. Short-acting repulsive forces.

Electrostatic repulsive forces are formed among vesicles upon addition of charged surfactants

to the double layer, enhancing the stability of the system. Biological stability of the niosomes

prepared with alkyl glycosides was investigated. They reported that niosomes were not stable

enough in plasma. This may be due to single–chain alkyl surfactants. SUVs were found to be

more stable. Niosomes in the form of liquid crystal and gel can remain stable at both room

temperature and at 4°C for 2 months. No significant difference has been observed between

the stability of these two types of niosomes with respect to leakage. Even though no

correlation between storage temperature and stability has been found, it is recommended that

niosomes be stored at 4°C. Ideally these systems should be stored dry for reconstitution by

nursing staff or by the patient and when rehydrated should exhibit dispersion characteristics

that are similar to the original dispersion. Simulation studies conducted to investigate

physical stability of these niosomes during transportation to the end-user revealed that

mechanical forces didn’t have any influence on physical stability.

It is assumed that the reason behind the stability of niosomes may be due to the prevention of

aggregation caused by steric interactions, among large polar head groups of surfactants.



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The factors which affect the stability of niosomes are as following.

• type of surfactant;

• nature of encapsulated drug;

• storage temperature;

• detergents;

• use of membrane spanning lipids;

• the interfacial polymerization of surfactant monomers in situ;

• inclusion of a charged molecule.

Applications of niosomes

The application of niosomal technology is wide and can be used to treat a number of diseases.

Niosomes as Drug Carriers

Niosomes have also been used as carriers for iobitridol, a diagnostic agent used for Xray

imaging. Topical niosomes may serve as solubilization matrix, as a local depot for sustained

release of dermally active compounds, as penetration enhancers, or as rate-limiting

membrane barrier for the modulation of systemic absorption of drugs.

Drug Targetting

One of the most useful aspects of niosomes is their ability to target drugs. Niosomes can be

used to target drugs to the reticuloendothelial system. The reticuloendothelial system (RES)

preferentially takes up niosomal vesicles. The uptake of niosomes is controlled by circulating

serum factors called opsonins. These opsonins mark the niosome for clearance. Such

localization of drugs is utilized to treat tumors in animals known to metastasize to the liver

and spleen. This localization of drugs can also be used for treating parasitic infections of the

liver. Niosomes can also be utilized for targeting drugs to organs other than the RES. A

carrier system can be attached to niosomes to target them to specific organs.[63] [73]

Anti-neoplastic Treatment

Most antineoplastic drugs cause severe side effects. Niosomes can alter the metabolism;

prolong circulation and half life of the drug, thus decreasing the side effects of the drugs.

Niosomes decrease rate of proliferation of tumor with higher plasma levels accompanied by

slower elimination. Tumoricidal activity of niosomally formulated methotrexate is higher as

compared to plain drug solution.[75] [76] [77]



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Leishmaniasis

Leishmaniasis is a disease in which a parasite of the genus Leishmania invades the cells of

the liver and spleen. Use of niosomes in tests conducted showed that it was possible to

administer higher levels of the drug without triggering the side effects, and thus allowed

greater efficacy in treatment.[74]

Delivery of Peptide Drugs

Oral peptide drug delivery has long been faced with a challenge of bypassing the enzymes

which would breakdown the peptide. Use of niosomes to successfully protect the peptides

from gastrointestinal peptide breakdown is being investigated. In an In vitro study conducted

by oral delivery of a vasopressin derivative entrapped in niosomes, significantly increased

stability of the peptide was shown.[78] [79]

Studying Immune Response

Due to their immunological selectivity, low toxicity and greater stability; niosomes are being

used to study the nature of the immune response provoked by antigens. Nonionic surfactant

vesicles have clearly demonstrated their ability to function as adjuvant following parenteral

administration with a number of different antigens and peptides.

Niosomes as Carriers for Haemoglobin

Niosomes can be used as carriers for haemoglobin within the blood. The niosomal vesicle is

permeable to oxygen and hence can act as a carrier for haemoglobin in anaemic patients.

Other Applications

a) Sustained Release

Sustained release action of niosomes can be applied to drugs with low therapeutic index and

low water solubility since those could be maintained in the circulation via niosomal

encapsulation.

b) Localized Drug Action

Drug delivery through niosomes is one of the approaches to achieve localized drug action,

since their size and low penetrability through epithelium and connective tissue keeps the drug

localized at the site of administration.



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Recent advances in niosomes

Combination of PEG and glucose conjugates on the surface of niosomes significantly

improved tumor targeting of an encapsulated paramagnetic agents assessed with MR imaging

in a human carcinoma xenograft model. Phase I and phase II studies were conducted for

Niosomal methotrexate gel in the treatment of localized psoriasis. These studies suggest that

niosomal methotrexate gel is more efficacious than placebo and marketed methotrexate gel

respectively. Acyclovir entrapped niosomes prepared by Hand shaking and Ether injection

methods increases the oral bioavailability. Lancome has come out with a variety of anti-

ageing products which are based on niosome formulations.

CONCLUSIONS

Niosomes have been proven to be useful in controlled drug delivery systems for transdermal,

parenteral, oral, and ophthalmic routes. They can be used to encapsulate anti-infective agents,

anti-cancer agents, anti-inflammatory agents and fairly recently as vaccine adjuvants.

Niosomes may enable targeting certain areas of the mammalian organisms and may be

exploited as diagnostic imaging agents. Niosomes are superior systems when compared to

other carriers with respect to stability, toxicity and cost-effectiveness. The problem of drug

loading remain to be addressed and although some new approaches have been developed to

overcome this problem, it is still necessary to increase encapsulation efficiencies as it is

important to maintain the biological potential of the formulations.

As the type of surfactant is one of the most important parameter affecting the formation of

the vesicles, as well as their toxicity and stability, the surfactants with the higher phase

transition should be selected as they yield more desirable permeability and toxicity profiles.

Transdermal, peroral, parenteral and ophthalmic routes are suitable for niosomal

applications. Recently, the use of niosomes as vaccines and radiodiagnostic agents have been

studied and found to be promising areas of application. Selection of a suitable drug to be

delivered via niosomes should be made taking into consideration that niosomes are capable of

encapsulating both hydrophobic and hydrophilic drugs.

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