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Niosome: A future of targeted drug delivery systems


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Over the past several years, treatment of infectious diseases and immunisation has undergone a revolutionary shift. With the advancement of biotechnology and genetic engineering, not only a large number of disease-specific biological have been developed, but also emphasis has been made to effectively deliver these biologicals. Niosomes are vesicles composed of non-ionic surfactants, which are biodegradable, relatively nontoxic, more stable and inexpensive, an alternative to liposomes. This article reviews the current deepening and widening of interest of niosomes in many scientific disciplines and, particularly its application in medicine. This article also presents an overview of the techniques of preparation of niosome, types of niosomes, characterisation and their applications.
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374 Journal of Advanced Pharmaceutical Technology & Research | Oct-Dec 2010 | Vol 1 | Issue 4
Niosome: A future of targeted drug delivery systems
The concept of targeted drug delivery is designed for
aempting to concentrate the drug in the tissues of interest
while reducing the relative concentration of the medication
in the remaining tissues. As a result, drug is localised on the
targeted site. Hence, surrounding tissues are not aected
by the drug. In addition, loss of drug does not happen due
to localisation of drug, leading to get maximum ecacy
of the medication. Dierent carriers have been used for
targeting of drug, such as immunoglobulin, serum proteins,
synthetic polymers, liposome, microspheres, erythrocytes
and niosomes.[1]
Niosomes are one of the best among these carriers. The
self-assembly of non-ionic surfactants into vesicles was
rst reported in the 70s by researchers in the cosmetic
industry. Niosomes (non-ionic surfactant vesicles) obtained
on hydration are microscopic lamellar structures formed
upon combining non-ionic surfactant of the alkyl or dialkyl
polyglycerol ether class with cholesterol.[2] The non-ionic
surfactants form a closed bilayer vesicle in aqueous media
based on its amphiphilic nature using some energy for
instance heat, physical agitation to form this structure.
In the bilayer structure, hydrophobic parts are oriented
away from the aqueous solvent, whereas the hydrophilic
heads remain in contact with the aqueous solvent. The
properties of the vesicles can be changed by varying
the composition of the vesicles, size, lamellarity, tapped
volume, surface charge and concentration. Various forces
act inside the vesicle, eg, van der Waals forces among
surfactant molecules, repulsive forces emerging from
the electrostatic interactions among charged groups of
surfactant molecules, entropic repulsive forces of the head
groups of surfactants, short-acting repulsive forces, etc.
These forces are responsible for maintaining the vesicular
structure of niosomes. But, the stability of niosomes are
affected by type of surfactant, nature of encapsulated
drug, storage temperature, detergents, use of membrane
spanning lipids, the interfacial polymerisation of surfactant
monomers in situ, inclusion of charged molecule. Due to
presence of hydrophilic, amphiphilic and lipophilic moieties
in the structure, these can accommodate drug molecules
with a wide range of solubility.[3] These may act as a depot,
releasing the drug in a controlled manner. The therapeutic
performance of the drug molecules can also be improved
by delayed clearance from the circulation, protecting the
drug from biological environment and restricting eects to
target cells.[4] Noisome made of alpha, omega-hexadecyl-
bis-(1-aza-18-crown-6) (Bola-surfactant)-Span 80-cholesterol
(2:3:1 molar ratio) is named as Bola-Surfactant containing
noisome.[5] The surfactants used in niosome preparation
should be biodegradable, biocompatible and non-
immunogenic. A dry product known as proniosomes may
Over the past several years, treatment of infectious diseases and immunisation has
undergone a revolutionary shift. With the advancement of biotechnology and genetic
engineering, not only a large number of disease-specific biological have been developed,
but also emphasis has been made to effectively deliver these biologicals. Niosomes
are vesicles composed of non-ionic surfactants, which are biodegradable, relatively
nontoxic, more stable and inexpensive, an alternative to liposomes. This article reviews
the current deepening and widening of interest of niosomes in many scientific disciplines
and, particularly its application in medicine. This article also presents an overview of
the techniques of preparation of niosome, types of niosomes, characterisation and
their applications.
Key words: Bilayer, drug entrapment, lamellar, niosomes, surfactants
Kazi Masud Karim, Asim Sattwa
Mandal, Nikhil Biswas, Arijit Guha,
Sugata Chatterjee, Mamata Behera,
Ketousetuo Kuotsu
Department of Pharmaceutical
Technology, Jadavpur University,
Kolkata – 700 032, West Bengal, India
J. Adv. Pharm. Tech. Res.
Address for correspondence
Dr. Ketousetuo Kuotsu, Department of Pharmaceutical
Technology, Jadavpur University, Kolkata - 700 032,
West Bengal, Kolkata, India. E-mail:
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Journal of Advanced Pharmaceutical Technology & Research | Oct-Dec 2010 | Vol 1 | Issue 4
Karim, et al.: Niosome – A future of targeted drug delivery systems
be hydrated immediately before use to yield aqueous
niosome dispersions. The problems of niosomes such as
aggregation, fusion and leaking, and provide additional
convenience in transportation, distribution, storage, and
Niosomes behave in vivo like liposomes, prolonging
the circulation of entrapped drug and altering its organ
distribution and metabolic stability.[7] As with liposomes,
the properties of niosomes depend on the composition
of the bilayer as well as method of their production. It is
reported that the intercalation of cholesterol in the bilayers
decreases the entrapment volume during formulation, and
thus entrapment eciency.[8]
However, differences in characteristics exist between
liposomes and niosomes, especially since niosomes
are prepared from uncharged single-chain surfactant
and cholesterol, whereas liposomes are prepared from
double-chain phospholipids (neutral or charged). The
concentration of cholesterol in liposomes is much more than
that in niosomes. As a result, drug entrapment eciency of
liposomes becomes lesser than niosomes. Besides, liposomes
are expensive, and its ingredients, such as phospholipids,
are chemically unstable because of their predisposition
to oxidative degradation; moreover, these require special
storage and handling and purity of natural phospholipids
is variable.
Niosomal drug delivery is potentially applicable to many
pharmacological agents for their action against various
diseases. It can also be used as vehicle for poorly absorbable
drugs to design the novel drug delivery system. It enhances
the bioavailability by crossing the anatomical barrier of
gastrointestinal tract via transcytosis of M cells of Peyer’s
patches in the intestinal lymphatic tissues.[9] The niosomal
vesicles are taken up by reticulo-endothelial system. Such
localised drug accumulation is used in treatment of diseases,
such as leishmaniasis, in which parasites invade cells of
liver and spleen.[10,11] Some non-reticulo-endothelial systems
like immunoglobulins also recognise lipid surface of this
delivery system.[2-8,10-12] Encapsulation of various anti-
neoplastic agents in this carrier vesicle has minimised drug-
induced toxic side eects while maintaining, or in some
instances, increasing the anti-tumour ecacy.[13] Doxorubicin,
the anthracycline antibiotic with broad-spectrum anti-
tumour activity, shows a dose-dependent irreversible
cardio-toxic eect.[14,15] Niosomal delivery of this drug to
mice bearing S-180 tumour increased their life span and
decreased the rate of proliferation of sarcoma. Intravenous
administration of methotrexate entrapped in niosomes to
S-180 tumour bearing mice resulted in total regression of
tumour and also higher plasma level and slower elimination.
It has good control over the release rate of drug, particularly
for treating brain malignant cancer.[16] Niosomes have been
used for studying the nature of the immune response
provoked by antigens.[17] Niosomes can be used as a carrier
for haemoglobin.[18,19] Vesicles are permeable to oxygen and
haemoglobin dissociation curve can be modied similarly
to non-encapsulated haemoglobin. Slow penetration of drug
through skin is the major drawback of transdermal route
of delivery.[20] Certain anti-inflammatory drugs like
urbiprofen and piroxicam and sex hormones like estradiol
and levonorgestrel are frequently administered through
niosome via transdermal route to improve the therapeutic
ecacy of these drugs. This vesicular system also provides
beer drug concentration at the site of action administered
by oral, parenteral and topical routes. Sustained release
action of niosomes can be applied to drugs with low
therapeutic index and low water solubility. Drug delivery
through niosomes is one of the approaches to achieve
localised drug action in regard to their size and low
penetrability through epithelium and connective tissue,
which keeps the drug localised at the site of administration.
Localised drug action enhances ecacy of potency of the
drug and, at the same time, reduces its systemic toxic eects,
eg, antimonials encapsulated within niosomes are taken up
by mononuclear cells, resulting in localisation of drug,
increase in potency, and hence decrease in dose as well as
toxicity.[13] The evolution of niosomal drug delivery
technology is still at the stage of infancy, but this type of
drug delivery system has shown promise in cancer
chemotherapy and anti-leishmanial therapy.
Based on the vesicle size, niosomes can be divided into
three groups. These are small unilamellar vesicles (SUV,
size=0.025-0.05 μm), multilamellar vesicles (MLV, size=>0.05
μm), and large unilamellar vesicles (LUV, size=>0.10 μm).
Methods of Preparation
Niosomes are prepared by dierent methods based on
the sizes of the vesicles and their distribution, number of
double layers, entrapment eciency of the aqueous phase
and permeability of vesicle membrane.
Preparation of small unilamellar vesicles
The aqueous phase containing drug is added to the mixture
of surfactant and cholesterol in a scintillation vial.[11] The
mixture is homogenised using a sonic probe at 60°C for 3
minutes. The vesicles are small and uniform in size.
Micro uidisation
Two uidised streams move forward through precisely
dened micro channel and interact at ultra-high velocities
within the interaction chamber.[21] Here, a common
gateway is arranged such that the energy supplied to the
system remains within the area of niosomes formation.
The result is a greater uniformity, smaller size and beer
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Karim, et al.: Niosome – A future of targeted drug delivery systems
Preparation of multilamellar vesicles
Hand shaking method (Thin lm hydration technique)
In the hand shaking method, surfactant and cholesterol
are dissolved in a volatile organic solvent such as diethyl
ether, chloroform or methanol in a rotary evaporator,
leaving a thin layer of solid mixture deposited on the wall
of the ask.[11] The dried layer is hydrated with aqueous
phase containing drug at normal temperature with gentle
Trans-membrane pH gradient (inside acidic) drug uptake process
(remote Loading)
Surfactant and cholesterol are dissolved in chloroform.[22]
The solvent is then evaporated under reduced pressure to
obtain a thin lm on the wall of the round-boom ask.
The lm is hydrated with 300 mM citric acid (pH 4.0) by
vortex mixing. The multilamellar vesicles are frozen and
thawed three times and later sonicated. To this niosomal
suspension, aqueous solution containing 10 mg/ml of drug
is added and vortexed. The pH of the sample is then raised
to 7.0-7.2 with 1M disodium phosphate. This mixture is
later heated at 60°C for 10 minutes to produce the desired
multilamellar vesicles.
Preparation of large unilamellar vesicles
Reverse phase evaporation technique (REV)
In this method, cholesterol and surfactant are dissolved in
a mixture of ether and chloroform.[23] An aqueous phase
containing drug is added to this and the resulting two
phases are sonicated at 4-5°C. The clear gel formed is further
sonicated aer the addition of a small amount of phosphate
buered saline. The organic phase is removed at 40°C under
low pressure. The resulting viscous niosome suspension
is diluted with phosphate-buered saline and heated in a
water bath at 60°C for 10 min to yield niosomes.
Ether injection method
The ether injection method is essentially based on slow
injection of niosomal ingredients in ether through a
14-gauge needle at the rate of approximately 0.25 ml/min
into a preheated aqueous phase maintained at 60°C.[11,24] The
probable reason behind the formation of larger unilamellar
vesicles is that the slow vapourisation of solvent results in an
ether gradient extending towards the interface of aqueous-
nonaqueous interface. The former may be responsible for
the formation of the bilayer structure. The disadvantages of
this method are that a small amount of ether is frequently
present in the vesicles suspension and is dicult to remove.
Multiple membrane extrusion method
A mixture of surfactant, cholesterol, and diacetyl phosphate
in chloroform is made into thin lm by evaporation.[20]
The lm is hydrated with aqueous drug solution and the
resultant suspension extruded through polycarbonate
membranes, which are placed in a series for up to eight
passages. This is a good method for controlling niosome
Niosome preparation using polyoxyethylene alkyl ether
The size and number of bilayer of vesicles consisting
of polyoxyethylene alkyl ether and cholesterol can be
changed using an alternative method.[25] Temperature
rise above 60°C transforms small unilamellar vesicles
to large multilamellar vesicles (>1 μm), while vigorous
shaking at room temperature shows the opposite eect, ie,
transformation of multilamellar vesicles into unilamellar
ones. The transformation from unilamellar to multilamellar
vesicles at higher temperature might be the characteristic
for polyoxyethylene alkyl ether (ester) surfactant, since it is
known that polyethylene glycol (PEG) and water remix at
higher temperature due to breakdown of hydrogen bonds
between water and PEG moieties. Generally, free drug is
removed from the encapsulated drug by gel permeation
chromatography dialysis method or centrifugation method.
Often, density differences between niosomes and the
external phase are smaller than that of liposomes, which
make separation by centrifugation very dicult. Addition
of protamine to the vesicle suspension facilitates separation
during centrifugation.
Emulsion method
The oil in water (o/w) emulsion is prepared from an organic
solution of surfactant, cholesterol, and an aqueous solution
of the drug.[26,27] The organic solvent is then evaporated,
leaving niosomes dispersed in the aqueous phase.
Lipid injection method
This method does not require expensive organic phase.
Here, the mixture of lipids and surfactant is rst melted
and then injected into a highly agitated heated aqueous
phase containing dissolved drug. Here, the drug can be
dissolved in molten lipid and the mixture will be injected
into agitated, heated aqueous phase containing surfactant.
Niosome preparation using Micelle
Niosomes may also be formed from a mixed micellar
solution by the use of enzymes. A mixed micellar solution
of C16 G2, dicalcium hydrogen phosphate, polyoxyethylene
cholesteryl sebacetate diester (PCSD) converts to a niosome
dispersion when incubated with esterases. PCSD is cleaved
by the esterases to yield polyoxyethylene, sebacic acid and
cholesterol. Cholesterol in combination with C16 G2 and
DCP then yields C16 G2 niosomes.
Characterisation of niosomes
Shape of niosomal vesicles is assumed to be spherical, and
their mean diameter can be determined by using laser light
scaering method.[28] Also, diameter of these vesicles can be
determined by using electron microscopy, molecular sieve
chromatography, ultracentrifugation, photon correlation
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Karim, et al.: Niosome – A future of targeted drug delivery systems
microscopy and optical microscopy[29,30] and freeze fracture
electron microscopy. Freeze thawing of niosomes increases
the vesicle diameter, which might be aributed to a fusion
of vesicles during the cycle.
Bilayer formation
Assembly of non-ionic surfactants to form a bilayer vesicle
is characterised by an X-cross formation under light
polarisation microscopy.[31]
Number of lamellae
This is determined by using nuclear magnetic resonance
(NMR) spectroscopy, small angle X-ray scattering and
electron microscopy.[29]
Membrane rigidity
Membrane rigidity can be measured by means of mobility
of uorescence probe as a function of temperature.[31]
Entrapment eciency
Aer preparing niosomal dispersion, unentrapped drug is
separated and the drug remained entrapped in niosomes
is determined by complete vesicle disruption using 50%
n-propanol or 0.1% Triton X-100 and analysing the resultant
solution by appropriate assay method for the drug.[32] It can
be represented as:
Entrapment eciency (EF) = (Amount entrapped / total
amount) × 100
In vitro Release Study
A method of in vitro release rate study was reported with
the help of dialysis tubing.[33] A dialysis sac was washed
and soaked in distilled water. The vesicle suspension was
pipeed into a bag made up of the tubing and sealed. The
bag containing the vesicles was then placed in 200 ml buer
solution in a 250 ml beaker with constant shaking at 25°C
or 37°C. At various time intervals, the buer was analysed
for the drug content by an appropriate assay method. In
another method, isoniazid-encapsulated niosomes were
separated by gel ltration on Sephadex G- 50 powder kept
in double distilled water for 48 h for swelling.[34] At rst, 1
ml of prepared niosome suspension was placed on the top
of the column and elution was carried out using normal
saline. Niosomes encapsulated isoniazid elutes out rst
as a slightly dense, white opalescent suspension followed
by free drug. Separated niosomes were lled in a dialysis
tube to which a sigma dialysis sac was aached to one end.
The dialysis tube was suspended in phosphate buer of
pH (7.4), stirred with a magnetic stirrer, and samples were
withdrawn at specic time intervals and analysed using
high-performance liquid chromatography (HPLC) method.
In vivo Release Study
Albino rats were used for this study. These rats were
subdivided with groups. Niosomal suspension used for
in vivo study was injected intravenously (through tail vein)
using appropriate disposal syringe.
Factors Affecting Physico-Chemical Properties of
Various factors that aect the physico-chemical properties
of niosomes are discussed further.
Choice of surfactants and main additives
A surfactant used for preparation of niosomes must have a
hydrophilic head and a hydrophobic tail. The hydrophobic
tail may consist of one or two alkyl or peruoroalkyl groups
or, in some cases, a single steroidal group.[35] The ether-type
surfactants with single-chain alkyl tail is more toxic than
corresponding dialkyl ether chain. The ester-type surfactants
are chemically less stable than ether-type surfactants and
the former is less toxic than the laer due to ester-linked
surfactant degraded by esterases to triglycerides and fay
acid in vivo.[36] The surfactants with alkyl chain length from
C12 to C18 are suitable for preparation of noisome. Span
series surfactants having HLB number between 4 and 8 can
form vesicles.[37] Dierent types of non-ionic surfactants
with examples are given in Table 1.[38]
The stable niosomes can be prepared with addition of
different additives along with surfactants and drugs.
The niosomes formed have a number of morphologies
and their permeability and stability properties can be
altered by manipulating membrane characteristics by
dierent additives. In case of polyhedral niosomes formed
from C16G2, the shape of these polyhedral niosomes
remains unaected by adding low amount of solulan C24
(cholesteryl poly-24-oxyethylene ether), which prevents
aggregation due to development of steric hindrance. In
contrast, addition of C16G2:cholesterol:solulan (49:49:2)
results in formation of spherical niosomes.[39] The mean
size of niosomes is inuenced by membrane composition.
Addition of cholesterol molecule to niosomal system makes
the membrane rigid and reduces leakage of drug from the
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 system.
Table 1: Different types of non-ionic surfactants
Type of non-ionic
Fatty alcohol Cetyl alcohol, stearyl alcohol, cetostearyl
alcohol, oleyl alcohol
Ethers Brij, Decyl glucoside, Lauryl glucoside,
Octyl glucoside, Triton X-100,
Esters Glyceryl laurate, Polysorbates, Spans
Block copolymers Poloxamers
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378 Journal of Advanced Pharmaceutical Technology & Research | Oct-Dec 2010 | Vol 1 | Issue 4
Karim, et al.: Niosome – A future of targeted drug delivery systems
Temperature change in the niosomal system affects
assembly of surfactants into vesicles and also induces vesicle
shape transformation.[35,39] A polyhedral vesicle formed by
C16G2:solulan C24 (91:9) at 25°C, on heating, transforms
into spherical vesicle at 48°C, but on cooling from 55°C, the
vesicle produces a cluster of smaller spherical niosomes at
49°C before changing into polyhedral structures at 35°C. In
contrast, the vesicle formed by C16G2:cholesterol:solulan
C24 (49:49:2) shows no shape transformation on heating
or cooling.[27] Along with the above-mentioned factors,
the volume of hydration medium and time of hydration
of niosomes are also critical factors. Improper selection of
these factors may result in the formation of fragile niosomes
or creation of drug leakage problems.
Nature of encapsulated drug
The physico-chemical properties of encapsulated drug
inuence charge and rigidity of the niosome bilayer. The
drug interacts with surfactant head groups and develops
the charge that creates mutual repulsion between surfactant
bilayers, and hence increases vesicle size.[29] The aggregation
of vesicles is prevented due to the charge development on
bilayer. The eect of the nature of drug on formation vesicle
is given in Table 2.
Factors affecting vesicles size, entrapment efficiency, and
release characteristics
Entrapment of drug in niosomes increases vesicle size,
probably by interaction of solute with surfactant head
groups, increasing the charge and mutual repulsion of
the surfactant bilayers, thereby increasing vesicle size. In
polyoxyethylene glycol (PEG)-coated vesicles, some drug
is entrapped in the long PEG chains, thus reducing the
tendency to increase the size. The hydrophilic lipophilic
balance of the drug aects the degree of entrapment.
Amount and type of surfactant
The mean size of niosomes increases proportionally with
increase in the hydrophilic-lipophilic balance (HLB) of
surfactants such as Span 85 (HLB 1.8) to Span 20 (HLB 8.6)
because the surface free energy decreases with an increase
in hydrophobicity of surfactants.[41] The bilayers of the
vesicles are either in the so-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. In the gel state, alkyl chains are present in a well
ordered structure, and in the liquid state, the structure of the
bilayers is more disordered. The surfactants and lipids are
characterised by the gel-liquid phase transition temperature
(TC). Phase transition temperature (TC) of surfactants also
aects entrapment eciency, ie, Span 60 having higher TC
provides beer entrapment.
Cholesterol content and charge
Inclusion of cholesterol in niosomes increases its
hydrodynamic diameter and entrapment efficiency. In
general, the action of cholesterol is twofold. On one hand,
cholesterol increases the chain order of liquid state bilayers,
and, on the other, it decreases the chain order of gel state
bilayers. At a high cholesterol concentration, the gel state
is transformed to a liquid-ordered phase. An increase in
cholesterol content of the bilayers resulted in a decrease in
the release rate of encapsulated material, and therefore an
increase in the rigidity of the resulting bilayers. The presence
of charge tends to increase the interlamellar distance
between successive bilayers in multilamellar vesicle
structure and leads to greater overall entrapped volume.[41]
Methods of Preparation
Hand shaking method forms vesicles with greater diameter
(0.35-13 nm) compared to the ether injection method
(50-1,000 nm). Small-sized niosomes can be produced by
Reverse Phase Evaporation (REV) method. Microuidisation
method gives greater uniformity and small-sized vesicles.
Resistance to osmotic stress
Addition of a hypertonic salt solution to a suspension of
niosomes brings about reduction in diameter. In hypotonic
salt solution, there is initial slow release with slight swelling
of vesicles, probably due to inhibition of eluting uid from
vesicles, followed by faster release, which may be due to
mechanical loosening of vesicles structure under osmotic
Table 3 lists drugs that have been used in animal study
through dierent routes.
Recent advancements in the eld of scientic research have
resulted in the endorsement of small molecules such as
proteins and vaccines as a major class of therapeutic agents.
These, however, pose numerous drug-associated challenges
such as poor bioavailability, suitable route of drug delivery,
physical and chemical instability and potentially serious
side eects. Opinions of the usefulness of niosomes in the
Table 2: Effect of the nature of drug on the
formation of niosomes
Nature of
the drug
from the
Stability Other
Decreased Increased Improved trans-
dermal delivery
Increased Decreased –
Decreased Increased
encapsulation, altered
Macromolecule Decreased Increased
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Journal of Advanced Pharmaceutical Technology & Research | Oct-Dec 2010 | Vol 1 | Issue 4
Karim, et al.: Niosome – A future of targeted drug delivery systems
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14. Cummings J, Stuart JF, Calman KC. Determination of adriamycin,
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16. Alcantar N, Dearborn K, VanAuker M, Toomey R, Hood E.
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bovine serum albumin. Immunology 1992;75:570-5.
18. Moser P, Marchand-Arvier M, Labrude P, Handjani -Vila RM,
Vignerson C. Hemoglobin niosomes. I. Preparation, functional
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20. Jayaraman SC, Ramachandran C, Weiner N. Topical delivery of
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study. J Pharm Sci 1996;85:1082-4.
21. Khandare JN, Madhavi G, Tamhankar BM. Niosomes novel drug
delivery system. East Pharmacist 1994;37:61-4.
22. Mayer LD, Bally MB, Hope MJ, Cullis PR. Uptake of antineoplastic
agents into large unilamellar vesicles in response to a membrane
potential. Biochem Biophys Acta 1985;816:294-302.
23. Naresh RA, Chandrashekhar G, Pillai GK, Udupa N. Antiinam-
matory activity of Niosome encapsulated diclofenac sodium with
Tween-85 in Arthitic rats. Ind J Pharmacol 1994;26:46-8.
24. Rogerson A, Cummings J, Willmo N, Florence AT. The distribu-
tion of doxorubicin in mice following administration in niosomes.
J Pharm Pharmacol 1988;40:337-42.
25. Pardakhty A, Varshosaz J, Rouholamini A. In vitro study of polyoxy-
ethylene alkyl ether niosomes for delivery of insulin. Int J Pharm
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of colchicines by a noisome system. Int J Pharm 2002;244:73-80.
27. Uchegbu IF, Vyas SP. Non-ionic surfactant based vesicles (nio-
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30. Azmin MN, Florence AT, Handjani-Vila RM, Stuart JF, Vanlerberghe
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ous non-ionic surfactants mixed with cholesterol. Colloids Surf B
Table 3: Drugs used in niosomal delivery
Routes of drug
Examples of Drugs
Intravenous route Doxorubicin, methotrexate, sodium
stibogluconate, iopromide, vincristine,
diclofenac sodium, flurbiprofen,
centchroman, indomethacin, colchicine,
rifampicin, tretinoin, transferrin and
glucose ligands, zidovudine, insulin,
cisplatin, amarogentin, daunorubicin,
amphotericin B, 5-fluorouracil,
camptothecin, adriamycin, cytarabine
Peroral route DNA vaccines, proteins, peptides, ergot
alkaloids, ciprofloxacin, norfloxacin,
Transdermal route Flurbiprofen, piroxicam, estradiol,
levonorgestrol, nimesulide, dithranol,
ketoconazole, enoxacin, ketorolac
Ocular route Timolol maleate, cyclopentolate
Nasal route Sumatriptan, influenza viral vaccine
Inhalation All-trans retinoic acids
delivery of proteins and biologicals can be unsubstantiated
with a wide scope in encapsulating toxic drugs such as
anti-AIDS drugs, anti-cancer drugs, and anti-viral drugs.
It provides a promising carrier system in comparison with
ionic drug carriers, which are relatively toxic and unsuitable.
However, the technology utilised in niosomes is still in its
infancy. Hence, researches are going on to develop a suitable
technology for large production because it is a promising
targeted drug delivery system.
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mice. J Pharm Pharmacol 1985;37:237-42.
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32. Balasubramaniam A, Kumar VA, Pillai KS. Formulation and in-vivo
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33. Yoshioka T, Stermberg B, Florence AT. Preparation and properties
of vesicles (niosomes) of sobitan monoesters (Span 20, 40, 60, and
80) and a sorbitan triester (Span 85). Int J Pharm 1994;105:1-6.
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characterization and tissue disposition of niosomes containing
isoniazid. Rasayan J Chem 2008;1:224-7.
35. Uchegbu FI, Vyas PS. Non-ionic surfactant based vesicles (nio-
somes) in drug delivery. Int J Pharm 1998;172:33-70.
36. Hunter CA, Dolan TF, Coombs GH, Baillie AJ. Vesicular system
(niosomes and liposomes) for delivery of sodium stibogluconate
in experimental murine visceral leishmaniasis. J Pharm Pharmacol
37. Yoshioka T, Florence AT. Vesicle (niosome)-in-water-in-oil (v/w/o)
emulsion an in-vitro study. Int J Pharm 1994;108:117-23.
38. Cooper and Gunn. Emulsions and cream. In: Carter SJ, editor.
Dispensing for Pharmaceutical Students. 12th edition. New York:
CBS Publishers and Distributors; 2000. P. 128.
39. Arunothayanun P, Bernard MS, Craig DQ, Uchegbu IF, Florence
AT. The eect of processing variables on the physical characteristics
of nonionic surfactant vesicles (niosomes) formed from hexadecyl
diglycerol ether. Int J Pharm 2000;201:7-14.
40. Rogerson A. Adriamycin-loaded niosomes–drug entrapment,
stability and release. J Microencap 1987;4:321-8.
41. Yoshioka T, Stermberg B, Florence AT. Preparation and properties
of vesicles (niosomes) of sobitan monoesters (Span 20, 40, 60, and
80) and a sorbitan triester (Span 85). Int J Pharm 1994;105:1-6.
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Source of Support: Nil, Conict of Interest: Nil.
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... According to the research, NS may extend the circulation of occluded medicines [7,8] and diagnostic markers [9]. NS are microscopic lamellar structures that form with the combination of cholesterol and a NIC surfactant of either the alkyl or dialkylpolyglycerol ether class [10]. The amphiphilic nature of NIC surfactants causes them to form a confined bilayer vesicle when used in aquatic circumstances. ...
... It is a common practice to administer specific anti-inflammatory drugs, such as flurbiprofen and piroxicam, plant extracts, and sex hormones, such as estradiol and levonorgestrel, through an NS via the transdermal route in order to improve their therapeutic efficacy [10,19,20]. The use of NS makes it possible to develop more comprehensive drug delivery strategies. ...
... It is possible to stabilise the vesicles using negative charge inducers such as dicetyl phosphate and dihexadecyl phosphate, while positive charge inducers such as stearylamine and cetylpyridinium chloride also aid in this process. Hydrophobic surfactants in NS prefer to face outwardly (toward the aqueous phase) in order to create closed bilayer structures, while NIC surfactants in NS prefer to face inward (more towards the aqueous phase) (toward each other) [10]. As a result, NS have hydrophilic inner and outer borders, with a lipophilic area in the middle of them. ...
Nanomedicine is a rapidly expanding field because of its benefits over conventional drug delivery technology, as it offers site-specific and target-oriented delivery of therapeutic agents. Nanoparticles and Nanocarriers Based Pharmaceutical Preparations presents a structured summary of recent advances and discoveries in nanomedicine and nanocarrier-based drug delivery. The book covers several key topics in a very simple and easy to understand language. Readers will be familiarized with many types of nanocarriers that have been developed over the past decade, the pharmaceutical formulations composed of organic and inorganic materials as well as their clinical benefits. Chapters are written with the help of authoritative sources of knowledge with the goal of building a foundational understanding of novel drug delivery systems. Since the subject matter is interdisciplinary, it will be of interest to students, teachers and researchers in a broad range of fields, including pharmaceutical sciences, nanotechnology, biomedical engineering and material sciences.
... They release the drug independent of pH, resulting in enhanced ocular bioavailability. Though, similar to liposomes, they are biodegradable, biocompatible, nontoxic, nonimmunogenic, and have good chemical stability, the efficacy of the niosomes as carriers for protein delivery to ocular tissues is still under investigation [223]. Discosomes, another modified version of niosomes, are an excellent strategy for ocular delivery. ...
... Discosomes, another modified version of niosomes, are an excellent strategy for ocular delivery. They are prepared using nonionic surfactants, with a size range of 12-16 nm, and prevent systemic drainage and, thus, improve the ocular residence time; however, they are nonbiodegradable and nonbiocompatible in nature [223]. Persistent protein expression after transfection of pDNA containing niosomes intravitreally for at least one month after injection was found to provide protection against enzymatic digestion and broad surface transfection in inner layer of retina with no cytotoxicity [224]. ...
Full-text available
Therapeutic proteins, including monoclonal antibodies, single chain variable fragment (ScFv), crystallizable fragment (Fc), and fragment antigen binding (Fab), have accounted for one-third of all drugs on the world market. In particular, these medicines have been widely used in ocular therapies in the treatment of various diseases, such as age-related macular degeneration, corneal neovascularization, diabetic retinopathy, and retinal vein occlusion. However, the formulation of these biomacromolecules is challenging due to their high molecular weight, complex structure, instability, short half-life, enzymatic degradation, and immunogenicity, which leads to the failure of therapies. Various efforts have been made to overcome the ocular barriers, providing effective delivery of therapeutic proteins, such as altering the protein structure or including it in new delivery systems. These strategies are not only cost-effective and beneficial to patients but have also been shown to allow for fewer drug side effects. In this review, we discuss several factors that affect the design of formulations and the delivery of therapeutic proteins to ocular tissues, such as the use of injectable micro/nanocarriers, hydrogels, implants, iontophoresis, cell-based therapy, and combination techniques. In addition, other approaches are briefly discussed, related to the structural modification of these proteins, improving their bioavailability in the posterior segments of the eye without affecting their stability. Future research should be conducted toward the development of more effective, stable, noninvasive, and cost-effective formulations for the ocular delivery of therapeutic proteins. In addition, more insights into preclinical to clinical translation are needed.
... Regarding niosomes, these are a form of LS composed of nonionic surfactants that generate vesicles with high stability, less toxicity, and more flexibility.Their production is also relatively simpler and less expensive.This kind of molecule can develop modifications into the SC barrier by combining with the lipids.They can also increase the SC smoothness by recovering missing lipids and reducing transepidermal water loss. These properties depend on several factors, such as physicochemical properties of the drug, the vesicle, and the lipids used to produce the niosomes (Kazi et al., 2010;Lasoń et al., 2016;Miastkowska and Sliwa, 2020). ...
... These carriers, named niosomes, consist of a single-chain surfactant coupled with cholesterol to form vesicles. Although they possess less cholesterol than liposomes [23], niosomes may be easily modified in relation to their cholesterol fraction, the type of surfactant, and the "critical packing parameter". The latter is a mathematical representation of surfactant aggregation determined by three parameters: lipid volume, optimal surface area, and critical chain length [24,25]. ...
Full-text available
Cardiotoxic therapies, whether chemotherapeutic or antibiotic, represent a burden for patients who may need to interrupt life-saving treatment because of serious complications. Cardiotoxicity is a broad term, spanning from forms of heart failure induction, particularly left ventricular systolic dysfunction, to induction of arrhythmias. Nanotechnologies emerged decades ago. They offer the possibility to modify the profiles of potentially toxic drugs and to abolish off-target side effects thanks to more favorable pharmacokinetics and dynamics. This relatively modern science encompasses nanocarriers (e.g., liposomes, niosomes, and dendrimers) and other delivery systems applicable to real-life clinical settings. We here review selected applications of nanotechnology to the fields of pharmacology and cardio-oncology. Heart tissue-sparing co-administration of nanocarriers bound to chemotherapeutics (such as anthracyclines and platinum agents) are discussed based on recent studies. Nanotechnology applications supporting the administration of potentially cardiotoxic oncological target therapies, antibiotics (especially macrolides and fluoroquinolones), or neuroactive agents are also summarized. The future of nanotechnologies includes studies to improve therapeutic safety and to encompass a broader range of pharmacological agents. The field merits investments and research, as testified by its exponential growth.
... 8−11 Being comparatively more versatile and stable, niosome vesicles have attracted attention as noncytotoxic replacements of the liposomes in similar applications. 12,13 The incorporation of small-molecule FRET pairs inside the niosomal membrane to study the microheterogeneity has been illustrated by several groups. 14−16 In most of the cases, the characteristics of the niosomal bilayer have been monitored by observing the FRET efficiency of the donor−acceptor dyes. ...
... By increasing the amount of cholesterol, the lipophilicity and stability of the two layers' increases, and the permeability decreases, so the drug can be more effectively trapped in the two layers of the vesicle 34 . But the large increase in the amount of cholesterol causes competition between the drug and cholesterol to be placed in the space between the two layers of niosomes, and the drug remains in the structure without encapsulation 35 . Cholesterol is one of the common materials used for the synthesis of stable niosomal formulations 36 . ...
Full-text available
Targeted drug delivery and increasing the biological activity of drugs is one of the recent challenges of pharmaceutical researchers. Niosomes are one of the new targeted drug delivery systems that enhances the biological properties of drugs. In this study, for the first time, the green synthesis of selenium nanoparticles (SeNPs), and its loading into niosome was carried out to increase the anti-bacterial and anti-cancer activity of SeNPs. Different formulations of noisome-loaded SeNPs were prepared, and the physical and chemical characteristics of the prepared niosomes were investigated. The antibacterial and anti-biofilm effects of synthesized niosomes loaded SeNPs and free SeNPs against standard pathogenic bacterial strains were studied, and also its anticancer activity was investigated against breast cancer cell lines. The expression level of apoptotic genes in breast cancer cell lines treated with niosome-loaded SeNPs and free SeNPs was measured. Also, to evaluate the biocompatibility of the synthesized niosomes, their cytotoxicity effects against the human foreskin fibroblasts normal cell line (HFF) were studied using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. The results illustrated that the optimal formulation had an average size of 177.9 nm, a spherical shape, and an encapsulation efficiency of 37.58%. Also, the results revealed that the release rate of SeNPs from niosome-loaded SeNPs and free SeNPs was 61.26% and 100%, respectively, in 72 h. Also, our findings demonstrated that the niosome-loaded SeNPs have significant antibacterial, anti-biofilm, and anticancer effects compared to the free SeNPs. In addition, niosome-loaded SeNPs can upregulate the expression level of Bax, cas3, and cas9 apoptosis genes while the expression of the Bcl2 gene is down-regulated in all studied cell lines, significantly. Also, the results of the MTT test indicated that the free niosome has no significant cytotoxic effects against the HFF cell line which represents the biocompatibility of the synthesized niosomes. In general, based on the results of this study, it can be concluded that niosomes-loaded SeNPs have significant anti-microbial, anti-biofilm, and anti-cancer effects, which can be used as a suitable drug delivery system.
... They found higher accumulation of drug in emul-gel formulation through skin retention studies by in vitro and in vivo experiments and concluded this formulation can be potential for topical delivery of CAP in anti psoriatic therapy. [121] A topical formulation of psoralene ethosomes were prepared to improve entrapment, skin permeation and deposition efficiency which was further evaluated real time drug release in vivo in rat model by microdialysis. During in vitro and in vivo studies, the group observed 6.56 times greater skin deposition of psoralen by ethosomes as well as area under curve and peak concentration Controlled drug release. ...
Full-text available
Nowadays, promising era for stepping towards the rapid development of the novel nanomedicine using nanotechnology to address various difficulties facing our human systems by treating and diagnosing. But before the great promise of nanotechnology for biological or biomedical applications can be completely realized, a number of issues need to be effectively resolved. This chapter will provide you with a summary of contemporary research results that explain the use and applications of various nanotechnologies and modified nanomaterials, which have created a possibility in the positive shift toward diagnosis and therapy. In addition to that, this chapter covers a wide range of nanoparticles as well as their applications in the field of biomedicine. In this chapter, the fundamental ideas behind the design of nanoparticle delivery systems, the interactions and movement of nanoparticles inside biological systems, and lastly, the potential applications of nanoparticles in industry and clinical practice are discussed in great detail. The primary focus of this discussion is on the biomedical application of inorganic (metal and metal oxide) and organic (carbon nanotubes and liposomes) nanoparticles and surfaces with nanopatterns in diagnostics, biosensing, and bioimaging devices, as well as drug delivery systems, theranostic systems, and bone-replacing implants.KeywordsNanoparticlesBiomedical applicationDrug deliveryTissue engineeringScaffolds
Vesicles (liposomes and niosomes) are bilayer membranous capsules composed of amphiphilic molecules having aqueous phase in their interior and can encapsulate drug ingredients to act as drug delivery systems, a bio-membrane model, and so on. Vesicles also find their applications in cosmetics and foods industries since they can not only entrap water-soluble substances in their core, but also solubilize oily substances in the bilayer membrane. Almost half a century has passed since the discovery of vesicles by Bangham, and research on their basic properties and applications has been gaining momentum once again. In this article, the preparation and properties of vesicles (liposomes, niosomes) with excellent dispersion stability, especially formed in mixtures of amphiphilic molecules, are reported. Furthermore, the preparation of nano-sized silica hollow particles using vesicles as a structure-directing agent and their application to anti-reflection film are also described. graphical abstract Fullsize Image
The current study intended to develop a new treatment of schizophrenia having a sustained release activity. Quetiapine fumarate (QF)-loaded polymer/lipid hybrid nanoparticulate systems of polycaprolactone (PCL) and Geleol™ were fabricated using polyvinyl alcohol (3% w/v). The proposed hybrid systems were formed conducting the emulsion/solvent evaporation procedure followed by evaluating their size, entrapment efficiency and in-vitro QF release. An optimum formulation (HF-G3; composed of PCL: Geleol™ in ratio 1:1 w/w) demonstrated small particle size (313 ± 8.59 nm) and high entrapment efficiency-values (99.68 ± 0.10%) and thus was selected for further studies. A sustained release profile was attained from the studied formulation where about 95% QF was released at 28 days. This study aims to assess the neuroprotective influence of the intramuscularly injected formulation (HF-G3) against cuprizone (CPZ)-induced schizophrenia in Swiss mice. Mice had CPZ (0.2%) in their diet for 21 days to induce schizophrenia. Mice were allocated into 4 groups: normal control, CPZ-fed, QF-treated and HF-G3/treated (10 mg/kg; twice per week) for 3 weeks. The behavioral alterations, the amounts of pro-inflammatory cytokines TNF-α and IL-1β besides the levels of glial fibrillary acidic protein (GFAP) and gamma-aminobutyric acid (GABA) were evaluated between the four groups. Results revealed the success of the optimum formulation in ameliorating the CPZ-induced behavioral disorders as well as in reducing the levels of cytokines, GABA and GFAP.
Full-text available
Non-ionic surfactant vesicles (or niosomes) are now widely studied as alternates to liposomes. An increasing number of non-ionic surfactant has been found to form vesicles, capable of entrapping hydrophilic and hydrophobic molecules. Isoniazid encapsulated as formulation using ethanol injection method. A different ratio of cholesterol was used. The formulated systems were characterized for in vitro by size distribution analysis, drug entrapment efficiency and drug release profiles. In vivo drug disposition was evaluated in normal, healthy albino rats for niosomal formulation. The size range 2. 28 ±0. 008(Plain Span 60), 2. 311±0. 009 (Span60: Cholesterol, 40:50), 2. 15±0. 002 (span60: Cholesterol 50:50). The entrapment release 74. 12% (Plain Span 60), 80. 23%(Span60: Cholesterol, 40:50), 76. 26% (span60: Cholesterol, 50:50). In vitro release pattern indicated that about total drug content were released within 48 h. The drug disposition by niosomal drug delivery proved that the drug accumulated in visceral organs (lung, kidney, liver, spleen) was lower than free drug. This proved that niosomal drug delivery system has lesser toxicity than free drug. From the present investigation, it can be concluded that the prepared niosomal drug delivery system of antitubercular agent such as isoniazid has exceptional potential for development into a low dose performed with effective treatment for tuberculosis.
Synthetic analogues of liposomes prepared from non-ionic surfactants, known as niosomes, have been used as vesicular drug carriers. Diclofenac sodium has been entrapped in niosomes comprising Tween 85 and Tween 85- poloxamer F 108 mixture. Anti-inflammatory efficacy of these niosomes were compared with that of free diclofenac sodium in adjuvant induced arthritic rats. It was found that the niosomal diclofenac sodium formulations prepared by employing a 1:1 combination of Tween 85 and poloxamer F 108 elicits a better and consistent anti-inflammatory activity for more than 72 hours after administration of a single dose.
The concept of carriers to deliver drugs to target organs and modify drug disposition has been widely discussed. The majority of such reports have concerned the use of phospholipid vesicles or liposomes, which exhibit certain disadvantages, such as chemical instability, high cost and variable purity of lipids used, which militates against their adoption as drug delivery vehicle. Alternatives to phospholipids are thus of interest from the technical viewpoint and could also allow a wider study of the influence of chemical composition on the biological fate of vesicles.
Withaferin A was entrapped in niosomes. The release of the drug from the niosome was slower compared to plain withaferin A dispersed in phosphate buffered saline. The mean survival time (MST) of the animals treated with withaferin A entrapped in the niosome was enhanced compared to the plain drugs.
Vesicles prepared from self-assembly of hydrated non-ionic surfactants molecules are called niosomes. These types of vesicles were first reported in the cosmetic industries. Niosomes exhibit more chemical stability than liposomes (a phospholipids vesicle) as non-ionic surfactants are more stable than phospholipids. Non-ionic surfactants used in formation of niosomes are polyglyceryl alkyl ether, glucosyl dialkyl ether, crown ether, polyoxyethylenealkyl ether, ester-linked surfactants, and steroid-linked surfactants and a spans, and tweens series. Niosomes preparation is affected by processes variables, nature of surfactants, and presence of membrane additives and nature of drug to be encapsulated. This review article presents an overview of theoretical concept of factors affecting niosome formation, techniques of noisome preparation, characterization of niosome, applications, limitations and market status of such delivery system.
The self assembly of non-ionic surfactants into vesicles was first reported in the seventies by researchers in the cosmetic industry. Since then a number of groups world wide have studied non-ionic surfactant vesicles (niosomes) with a view to evaluating their potential as drug carriers. This article presents a summary of the achievements in the field to date. Niosomes may be formed form a diverse array of amphiphiles bearing sugar, polyoxyethylene, polyglycerol, crown ether and amino acid hydrophilic head groups and these amphiphiles typically possess one to two hydrophobic alkyl, perfluoroalkyl or steroidal groups. The self assembly of surfactants into niosomes is governed not only by the nature of the surfactant but by the presence of membrane additives, the nature of the drug encapsulated and the actual method of preparation. Methods of niosome preparation and the number of different morphologies that have been identified are detailed. The influence of formulation factors on niosome stability is also examined as are methods to optimise drug loading. In vivo these systems have been evaluated as immunological adjuvants, anti-cancer/anti-infective drug targeting agents and carriers of anti-inflammatory drugs. Niosomes have also been used in diagnostic imaging. Efforts to achieve transdermal and ophthalmic drug delivery with some formulations are also discussed.