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IJRPC 2012, 2(2) Nasir et al ISSN: 22312781

INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY

Available online at www.ijrpc.com Review Article

NIOSOMES: AN EXCELLENT TOOL FOR DRUG DELIVERY


Ali Nasir*, Harikumar SL and Kaur Amanpreet
1
Department of Pharmaceutics, Rayat and Bahra Institute of Pharmacy, Sahauran, Distt.
Mohali, Punjab, India.

ABSTRACT
Design and development of novel drug delivery system (NDDS) has two prerequisites. First, it
should deliver the drug in accordance with a predetermined rate and second it should release
therapeutically effective amount of drug at the site of action. Conventional dosage forms are
unable to meet these requisites. Niosomes are essentially non-ionic surfactant-based
multilamellar or unilamellar vesicles in which an aqueous solution of solute is entirely enclosed
by a membrane resulting from the organisation of surfactant macromolecules as bilayer.
Niosomes are formed on hydration of non-ionic surfactant film which eventually hydrates
imbibing or encapsulating the hydrating aqueous solution. The proposed review deals with
composition, methods of preparation, and applications of niosomes in the pharmaceutical field.
The main aim of development of niosomes is to control the release of drug in a sustained way,
modification of distribution profile of drug and for targeting the drug to the specific body site.

INTRODUCTION ADVANTAGES
Vesicular systems are a novel means of drug The application of vesicular (lipid vesicles and
delivery that can enhance bioavailability of non-ionic surfactant vesicles) systems for
encapsulated drug and provide therapeutic therapeutic purpose may offer several
activity in a controlled manner for a prolonged advantages: -
period of time. Niosomes are nonionic 1. High patient compliance in comparison
surfactant vesicles in aqueous media resulting with oily dosage forms as the vesicle
in closed bilayer structures that can be used suspension is a water–based vehicle.
as carriers of amphiphillic and lipophilic drugs 2. Accommodate drug molecules with a wide
1
.Niosomes are microscopic lamellar range of solubilities.
structures formed on admixture of non-ionic 3. The characteristics of the vesicle
surfactant of the alkyl or dialkyl polyglycerol formulation are variable and controllable.
ether class and cholesterol and the enclosed Altering vesicle composition, size,
interior usually contains a buffer solution at lamellarity, surface charge and
2
appropriate pH . In niosomes, the vesicles concentration can control the vesicle
forming amphiphile is a non-ionic surfactant characteristics.
stabilized by addition of cholesterol and small 4. The vesicles may act as a depot, releasing
amount of anionic surfactant such as dicetyl the drug in a controlled manner.
phosphate3. Non-ionic surfactants provide a 5. They are osmotically active and stable, as
few advantages over the phospholipids well as they increase the stability of
because they are more economical and are entrapped drug.
chemically more stable as they are not easily 6. Handling and storage of surfactants
hydrolysed or oxidised during storage. The requires no special conditions.
vesicular structure can be modified to provide 7. They improve oral bioavailability of poorly
sustained or controlled drug delivery thus absorbed drugs and enhance skin
enhancing efficacy of system for prolonged penetration of drugs.
periods 4. 8. They can be made to reach the site of
action by oral, parenteral as well as topical
routes.

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9. The surfactants are biodegradable, Solulan C24 poly-24-oxyethelene cholesteryl


biocompatible and non-immunogenic. ether has been reported to form spherical,
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tubular or polyhedral niosomal vesicles .
NIOSOME FORMATION Another class of non-ionic surfactants is
Theoretically, niosomal formation requires the polyoxyethylene alkyl ethers (CnEOm , Brij TM)
presence of a particular amphiphile and which have ability to form bilayer vesicles
aqueous solvent. The association of when mixed with cholesterol. The different
amphiphile monomers into vesicles on grades of Brij used for vesicle formation are
hydration is the result of a high interfacial Brij 30, 35, 52, 58, 72, 76, 92, and 97.
tension between water and hydrocarbon Numerous studies have been reported in
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portion (or any other hydrophobic group) of the literature using these surfactants .
amphiphile, causing them to associate. New surfactants like bola surfactants have
Simultaneously, the steric hydrophilic and ionic been synthesized with the aim of preparing
repulsion between the head groups ensure innovative niosomal systems. Bola forms
that these groups are in contact with water. amphiphiles are composed of two identical
These two opposite forces lead to a AZA- Crown ether units, as polar heads, linked
supramolecular assembly. The essential to a long alkyl chain and represent a new class
components in the preparation of niosomes of non-ionic surfactants, which are able to
are membrane additives such as cholesterol assemble in colloidal structures if associated
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and non-ionic surfactants. with cholesterol .
Another category of surfactants Wasag®7
Cholesterol (70% stearate sucrose ester, 30% palmitate
®
Cholesterol is a waxy steroid metabolite found sucrose ester) and Wasag 15 (70% stearate
in the cell membranes. Cholesterol is added sucrose ester, 30% palmitate sucrose ester)
usually to the non-ionic surfactants to give have been investigated for entrapment of
rigidity and orientational order to the niosomal ovalbumin niosomes. These sucrose ester
5
bilayer . Cholesterol and its derivatives are the surfactants are easily biodegradable and
most common additives found in niosomal posses very low toxicity. Moreover they are
systems. Cholesterol enables the formation of able to form gel state bilayer at 37oC12.
vesicles, reduces aggregation and provides
greater stability. Cholesterol is also known to Other additives
abolish gel to liquid phase transition of Charge inducers are one of the membrane
niosomal systems resulting in niosomes that additives which are often included in niosomes
6
are less leaky . because they increase surface charge density
and prevent vesicles flocculation, aggregation
Non-ionic surfactants and fusion. Negatively and positively charged
Non-ionic surfactants act as main component molecules are used for induction of charge in
in niosomal formulations. Generally, they niosomes as reported by number of scientists.
possess hydrophilic head group and a Dicetyl phosphate (DCP) and stearyl amine
hydrophobic tail. The hydrophobic moiety may (SA) which induces negative or positive
consist of 1/2/3 alkyl chains or per fluro group charge is examples of such membrane
or in certain cases a single stearyl group. The additives.
alkyl group chain length is from C12- C18.
Perfluro alkyl group surfactants have chain METHODS OF PREPARATION
length having C10. Crown ether amphiphile The general method of preparation of
bears a steroidal group. niosomes involves evaporation to produce a
Sorbitan fatty acid esters are most commonly lipid film followed by hydration with the
used surfactants found in literature. Most hydration medium. However, there are
commonly used Spans are Span 20, 40, 60, variants of this method that are described here
65, 80, and 85. All Span types have the same in detail.
head group and different alkyl chain length. It
was reported that increasing alkyl chain length Lipid film hydration (Hand shaking method)
leads to high entrapment efficiency of drug7. In this method, surfactants/lipids are casted as
A number of researchers investigated Tweens layers of film from their organic solution using
as non-ionic surfactants in niosomes flask rotary evaporator under reduced
formation. Most commonly reported Tweens in pressure (or by hand shaking) and then casted
niosomal preparations are Tween 20, Tween films are dispersed in an aqueous medium.
40, and Tween 60.Tweens are polysorbates Upon hydration, the lipids swell and peel off
derived from PEGylated sorbitan esterified from the wall of the round bottom flask at
8
with fatty acids . temperature slightly above the phase transition

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temperature of surfactants used, for specified Trans membrane pH gradient (inside


period of time (time of hydration) with constant acidic) Drug Uptake Process (Remote
mild shaking. The mechanical energy required Loading)
for the swelling of the lipids and dispersion of In remote loading process surfactants and
casted lipid film is imparted by manual cholesterol are dissolved in chloroform. The
agitation (hand shaking) or by exposing the solvent is then evaporated under reduced
film to a stream of water saturated nitrogen for pressure to get a thin film on the wall of the
15 minutes followed by swelling in aqueous round bottom flask. The film is hydrated with
medium without shaking (non shaken 300 mM citric acid (pH 4.0) by vortex mixing.
vesicles). Hand shaking method produces The multilamellar vesicles are frozen and
multi lamellar vesicles (MLVs) while vesicles thawed 3 times and later sonicated. To this
produced by non shaking method are large niosomal suspension, aqueous solution
unilamellar vesicles LUVs13. containing 10 mg/ml of drug is added and
vortexed. The pH of the sample is then raised
Reverse phase evaporation to 7.0-7.2 with 1M disodium phosphate. This
The novel key in this method is the removal of mixture is later heated at 60°C for 10 minutes
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solvent from an emulsion by evaporation. The to produce niosomes .
surfactant and cholesterol are dissolved in
ether or chloroform or in a mixture of Multiple membrane extrusion method In
chloroform and ether chloroform with or membrane extrusion method, the size of
without drug. The resulting two-phase system niosomes is reduced by passing them through
is then homogenized using homogenizer. The membrane filter. This method can be used for
organic phase is removed under reduced production of multi lamellar vesicles as well as
pressure to form niosomes dispersed in large unilamellar vesicles. It is found as a good
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aqueous phase. In some cases, resulting method for controlling niosomal size .
suspensions must be further hydrated or
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homogenized to yield niosomes . Ethanol injection method
This method has been reported as one of the
The Bubble method It is novel technique for alternatives used for the preparation of small
one step preparation of liposomes and unilamellar vesicles (SUVs) without sonication.
niosomes without the use of organic solvents. In this method, an ethanol solution of
The bubbling unit consists of round-bottomed surfactant is injected rapidly through a fine
flask with three necks positioned in water bath needle into excess of saline or other aqueous
to control the temperature. Water-cooled reflux medium. Vaporization of ethanol leads to the
and thermometer is positioned in the first and formation of vesicles. Enoxacin was entrapped
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second neck and nitrogen is supplied through in niosomes using this particular method .
the third neck. Researchers dispersed
cholesterol and surfactants together in buffer Ether injection method
(pH 7.4) at 70°C, the dispersion is mixed for This method was reported in 1976 by Deamer
15 seconds with high shear homogenizer and and Bangham. It is similar to ethanol injection
immediately afterwards “bubbled” at 70°C method; however it differs with ethanol
15
using nitrogen gas . injection method in many ways. It involves
injection of immiscible organic solution
Microfludisation containing surfactant or surfactant-cholesterol
This is a recent technique to prepare small or surfactant cholesterol-diacetyl phosphate or
multi lamellar vesicles. A microfludizer is used surfactant cholesterol- drug solution mixture
to pump the fluid at a very high pressure very slowly into an aqueous phase through a
(10,000 psi) through a 5 pm screen. narrow needle at vaporization temperature of
Thereafter; it is forced along defined micro organic solvent. Vaporization of ether leads to
channels, which direct two streams of fluid to the formation of single layered vesicles
collide together at right angles, thereby (SLVs). It has a little risk of causing oxidative
affecting a very efficient transfer of energy. degradation provided ether is free from
The lipids can be introduced into the fluidizer. peroxides. The disadvantage of this method is
The fluid collected can be recycled through the that a small amount of ether is often present in
pump until vesicles of spherical dimensions the vesicles suspension and is difficult to
20
are obtained. This method resulted in remove very often .
niosomes with greater uniformity and small
16
size which shows better reproducibility . Formation of niosomes from proniosomes
Another method of producing niosomes is to
coat a water-soluble carrier such as sorbitol

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with non-ionic surfactants. The result of the and prolong the existence of the drug in the
coating process is a dry formulation in which systemic circulation. Niosomes were prepared
each water-soluble particle is covered with a from Span40, Span60, and Cholesterol using
thin film of dry surfactant. This preparation is reverse evaporation method. The in vitro
termed as “proniosomes”. The niosomes are release study signifies sustained release
recognized by the addition of aqueous phase profile of niosomal dispersions. Release profile
at (T > Tm) and brief agitation simultaneously. of prepared formulations has shown that more
T=Temperature. than 85.2±0.015% drug was released in 24 h
21
Tm = mean phase transition temperature . with zero-order release kinetics. The results
obtained also revealed that the types of
Sonication Method surfactant and Cholesterol content ratio
The size range of niosomes has a major effect altered the entrapment efficiency, size, and
on their in-vitro in-vivo fate. Hence, size drug release rate from niosomes23. Niosomal
reduction of niosomes is essential after formulation could be promising delivery
hydration stage. Niosomes prepared by system for gliclazide with improved
reverse phase evaporation and hand-shaking bioavailability and prolonged drug release
method are usually in micron size range (1.15 profile. Gliclazide-loaded niosomes were
and 2.75mm). By using sonication technique, formulated and evaluated for their in-vitro as
size of niosomes formed by hand shaking can well as in-vivo characteristics in an attempt to
be reduced to 100-140 nm. In this method, improve the oral bioavailability of the drug. The
average size of vesicles can be reduced by in-vitro release studies of drug from niosomes
providing high energy by sonication. This is exhibited a prolonged drug release as
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done by exposure of multi lamellar vesicles to observed over a period of 24 hrs .
ultrasonic irradiation. Sonication method is
most widely used for producing small vesicles. Transdermal Delivery
There are two types of sonication based on Slow penetration of drug through skin is the
the use of either probe or bath ultrasonic major drawback of transdermal route of
disintegrators. The probe is employed for delivery. An increase in the penetration rate
dispersions, which require high energy in small has been achieved by transdermal delivery of
volume while bath is more suitable for large drug incorporated in niosomes. Niosomes of
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volume . terbinafine hydrochloride was formulated by
thin film hydration method using different ratios
APPROACHES OF NIOSOMES of non-ionic surfactants (Tween 20, 40, 60,
The administration of niosomes by various and 80) and cholesterol with constant drug
routes has been reported and it is clear that concentration. Niosomal preparations were
the route is important in designing a vesicular tested for in-vitro antifungal activity using the
formulation. strain Aspergillus niger and compared with
pure drug solution (as standard). All the
Oral Route Delivery niosomal formulations showed gradual
Niosomes can be proposed as a potential oral increase in zone of inhibition due to the
delivery system for the effective delivery of controlled release of medicament. The studies
drugs. The delivery of biopharmaceuticals to revealed that gel containing total niosomes
the systemic circulation through oral possess maximum zone of inhibition values
administration is hindered by numerous (12mm) initially followed by sustained release
barriers, including pH gradients, proteolytic (12mm-16mm) compared to gel containing
enzymes and low epithelial permeability. The drug entrapped niosomes, gel containing pure
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oral delivery of recombinant human insulin drug and marketed preparation . Proniosomal
using niosomal formulations was gels of flurbiprofen were developed using
demonstrated by a study involving different spans with and without cholesterol.
polyoxyethylene alkyl ethers based niosomes. Niosomes were formed by hydrating
Entrapment of insulin in bilayer structure of proniosomes. Results indicated that the
niosomes protected it against proteolytic entrapment efficiency followed the trend Sp 60
activity of α-chymotrypsin, trypsin and pepsin (C18)>Sp 40 (C16)>Sp 20 (C12)>Sp 80 (C18).
in vitro. Significantly higher protection activity Cholesterol increased or decreased the
was seen in Brij 92/cholesterol (7:3 molar entrapment efficiency depending on either the
ratios) in which only 26.3±3.98% of entrapped type of the surfactant used or its concentration
insulin was released during 24 h in simulated within the formulae. Increasing total lipid or
10
intestinal fluid (SIF) . Encapsulation of drug concentration also increased the
Ganciclovir in lipophilic vesicular structure may entrapment efficiency of flurbiprofen into
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be expected to enhance the oral absorption niosomes . Benzoyl peroxide was entrapped

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30
into niosomes by thin film hydration technique, preserved with Span 40 niosomes .
and various process parameters were Niosomes of cisplatin were prepared using
optimized by partial factorial design. The Span 60 and cholesterol and investigated for
optimized niosomal formulation was antimetastatic activity in experimental
incorporated into HPMC K15 gel and metastatic model of B16F10 melanoma.
extensively characterized for percentage drug Treatment with niosomal cisplatin (1 mg/kg)
entrapment (PDE) and in vitro release and combination of the same with theophylline
performance. The present study demonstrated (15 mg/kg) showed significant reduction in the
prolongation of drug release, increased drug number of lung nodules as compared to
retention into skin, and improved permeation untreated control as well as free cisplatin (1
across the skin after encapsulation of benzoyl mg/kg). The treatment with activated
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peroxide into niosomal topical gel . macrophages (activated by using Muramyl
Entrapment of drug Erythromycin into dipeptide) significantly reduced the secondary
niosomes showed prolongation of drug growth of tumor in lung. Niosomal cisplatin
release, enhanced drug retention into skin and showed a significant protection against weight
improved permeation across the skin after loss and bone marrow toxicity as compared to
28 31
encapsulation . free cisplatin .

Leishmaniasis Delivery of peptide drugs


Niosomes can be used for targeting of drug in The ability of non-ionic surfactant vesicles to
the treatment of diseases in which the enhance antibody production against bovine
infecting organism resides in the organ of serum albumin (BSA) was compared with
reticulo-endothelial system. Leishmaniasis is Freund’s complete adjuvant (FCA), in the
such a disease in which parasite invades cells BALB/c mouse. The adjuvant activity of
of liver and spleen. The commonly prescribed niosomes was wholly dependent on the BSA
drugs are antimonials, which are related to entrapped within vesicles although mixing free
arsenic, and at high concentration they BSA with vesicles was not effective. Analysis
damage the heart, liver and kidney. Liver and of anti BSA IgG subclasses induced by
serum concentrations of antimony in the niosomes and FCA showed that niosomes
mouse have been determined after were generally better stimulators of IgG2a
administration of sodium stibogluconate in the than was FCA, but poorer stimulators of
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free, liposomal and niosomal form. High liver IgG1 . In another study, the structure
and low serum values were attained by the behaviors of hemoglobin (Hb) and the
use of both vesicular formulations. Niosomal interactions of the niosome with Hb are
sodium stibogluconate was shown to be more studied in PEG 6000/Tween 80/Span 80/H2O
active than free drug against experimental niosomal system. The obtained results
murine visceral leishmaniasis, an effect showed that Hb can be adsorbed and
apparently dependent on maintaining high outspread on the surface of the niosome
drug levels in the infected reticuloendothelial membrane. The behaviors of Hb are partially
29
system . stabilized and protected in Hb/niosome
system. This study can be helpful to
Neoplasia understand deeply the structure and functions
Numerous attempts have been made to of biological membrane in life system, and the
33
enhance the selectivity of antinioplastic agents relation of protein properties with vesicles .
by linking them to a cancer moiety. Novel PEGylated niosomes showed a promising
vesicular systems, niosomes containing drug delivery systems for improved
anticancer drugs if suitably designed will be oligonucleotides potency. Polyethylene glycol
expected to accumulate within tumors. (PEG) modified cationic niosomes were used
Niosomal formulations of paclitaxel (PCT), an to improve the stability and cellular delivery of
antineoplastic agent, were preared using oligonucleotides (OND). PEG-modification
different surfactants by film hydration method. significantly decreased the binding of serum
PCT was successfully entrapped in all of the protein and prevented particle aggregation in
formulations. The slow release observed from serum. The loaded nuclear acid drug exhibited
these formulations might be beneficial for increased resistance to serum nuclease.
reducing the toxic side effects of PCT. The Compared with cationic niosomes, the
efficiency of niosomes to protect PCT against PEGylated niosomes showed a higher
34
gastrointestinal enzymes (trypsin, efficiency of OND cellular uptake in serum .
chymotrypsin, and pepsin) was also evaluated
for PCT oral delivery. Among all formulations,
gastrointestinal stability of PCT was well

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Hormone delivery immunization. Non-ionic surfactant vesicles of


The in-vitro permeation of estradiol from influenza antigen for nasal mucosal delivery
vesicular formulations through human stratum were studied. The study described the
corneum was studied. The vesicles were encapsulation of viral influenza vaccine
composed of non-ionic n-alkyl polyoxyethylene antigen in non-ionic surfactant vesicles using
ether surfactants (CnEOm). Two mechanisms dehydration-rehydration technique. Influence
are proposed to play an important role in of the varying proportion of surfactant,
vesicle–skin interactions, i.e., the penetration cholesterol, and dicetyl phosphate on the
enhancing effect of surfactant molecules and morphology, particle size, entrapment
the effect of the vesicular structures caused by efficiency, and in-vitro antigen release from
their adsorption at the stratum corneum– niosomes was investigated. The stability of the
35
suspension interface . antigen was studied using sodium dodecyl
sulphate (SDS)-polyacrylamide gel
Cosmetic delivery electrophoresis and immunoblotting.
The first report of non-ionic surfactant vesicles Researchers also studied the effect of
came from the cosmetic applications devised cholesterol concentration and the method of
by L’Oreal. Niosomes were developed and lyophilization on antigen loading and in-vitro
39
patented by L’Oréal in the 1970s and 80s. The release of antigen from surfactant vesicles .
first product ‘Niosome’ was introduced in 1987 Niosomes for topical DNA delivery of Hepatitis
by Lancôme. The advantages of using B surface antigen (HBsAg) were prepared by
niosomes in cosmetic and skin care reverse phase evaporation method using Span
applications include their ability to increase the 85 and cholesterol. The immune stimulating
stability of entrapped drugs, improved activity was investigated and it was observed
bioavailability of poorly absorbed ingredients that topical niosomes elicited a comparable
36
and enhanced skin penetration . serum antibody titer and endogenous
cytokines levels as compared to intramuscular
40
Diagnostic markers recombinant HBsAg and topical liposomes .
Encapsulation of radio opaque agent,
iopromide into niosomes using cholesterol and Advances in niosomal delivery
stearylamine which were found to concentrate Glucose-targeted niosomes to deliver
in the kidneys on intravenous vasoactive intestinal peptide (VIP) to the brain
125
administrationwas studied. The positive was investigated. VIP/ I-VIP-loaded glucose-
charge on the niosomal surface was found to bearing niosomes were intravenously injected
be responsible for kidney targeting. C16G3 to mice. Brain uptake was determined by
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niosomes resulted in highest kidney iopromide measuring the radioactivity of I-labeled VIP
concentration owing to less fluid bilayer than using γ-counting, after intravenous
the C16C12G7. Although, the niosomal administration of VIP in solution or
formulation enhanced the opacity of this encapsulated in glucose-bearing niosomes or
contrast agent, but clinically relevant in control niosomes. Brain distribution of intact
enhancement of opacity was not achieved in VIP after injection of glucose-bearing
this study due to poor encapsulation efficiency niosomes, indicated that radioactivity was
37
of the agent . preferentially located in the posterior and the
A diagnostic agent, iobitridol used for X-ray anterior parts of the brain, whereas it was
imaging was encapsulated in niosomes by homogeneously distributed in the whole brain
film-hydration method. The niosomal vesicles after the administration of control vesicles41.
were prepared using appropriate mixtures of Polyoxyethylene monostearyl ether niosomes
D-alpha tocopheryl polyethylene glycol 1000 using super critical carbon dioxide were
succinate, polyoxyethylene glycol 4000 prepared and characterized. The niosomes
stearate, sorbitan monostearate, cholesterol were formed in super critical carbon dioxide
and dicetylphosphate and further fluids without any organic solvent like ethanol
characterized for the physico-chemical and that is essential for their preparation by
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morphological properties . conventional methods. Higher entrapment
efficiency was achieved near phase transition
Vaccine delivery temperature. When CO2 was introduced into
An interesting group of vaccine carrier the cell kept at a constant volume, the
systems are formulations based on non-ionic entrapment efficiency of niosomes showed a
surfactant vesicles (niosomes) which maximum value on the C18EO6 solubility
themselves are only weekly immunogenic. boundary line in CO2, while it increased with
Niosomes are gaining wide attention as increase in preparation pressure at varying cell
peroral vaccine delivery system and for topical

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volume and a constant CO2 amount as C18EO6 aceclofenac. Dig J Nanomater Bios.
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completely dissolved in supercritical CO2 . 2010; 5(1): 249-254.
9. Uchegbu IF, McCarthy D, Schatzlein
CONCLUSION A, Florence AT. Phase transitions in
The concept of incorporating the drug into aqueous dispersions of the hexadecyl
liposomes or niosomes for a better targeting of diglycerol ether (C16G2) non-ionic
the drug at appropriate tissue destination is surfactant, cholesterol and cholesteryl
widely accepted by researchers and poly-24-oxyethylene ether: vesicles,
academicians. Niosomes represent a tubules, discomes and micelles. STP
promising drug delivery module. They Pharma Sci. 1996; 6: 33–43.
presents a structure similar to liposome and 10. Pardakhty A, Varshosaz J,
hence they can represent alternative vesicular Rouholamini A. In vitro study of
systems with respect to liposomes, due to the polyoxyethylene alkyl ether niosomes
niosome ability to encapsulate different type of for delivery of insulin. Int J Pharm.
drugs within their multienvironmental structure. 2007; 328: 130–141.
The usefulness of niosomes in the delivery of 11. Muzzalupo R, Ranieri GA, La Mesa C.
proteins and biologicals can be Translational diffusion and other
unsubstantiated with a wide scope in physicochemical properties of a
encapsulating toxic drugs such as anti-cancer bolaform surfactant in solution.
drugs and anti-viral drugs. Niosomes are Langmuir. 1996; 12: 3157–3161.
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ophthalmic, topical, parentral, etc. 13. Azmin MN, Florence AT, Handjani-
Vila RM, Stuart JFB, Vanlerberghe G,
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