Niosomes
(Targeted
drug delivery systems)
Niosomes
• Medication
is encapsulated in a vesicle
• Composed
of a bilayer of non-ionic surface active agents
• They
are vesicles composed of non-ionic surfactants
• Biodegradable,
relatively nontoxic, more stable and
inexpensive
• Used
as an alternative to liposomes
Advantages of niosomes
• These
are very small in size -nanometric scale
• Structurally
similar to liposomes, but offer several advantages over them
• Niosomes
greatly increase transdermal drug delivery and
also in targeted drug delivery
• Hydrophilic,
lipophilic and amphiphilic drugs can be accommodated in the vesicular moieties
• Act
as a depot to release the drug slowly and offer
a controlled release
• Increase
the stability of the entrapped drug
• Handling
and storage of surfactants
do not require any special conditions
• Enhance
the skin penetration of drugs
Structure of niosomes
Ø Niosomes
are microscopic lamellar structures
Ø Formed
on the 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
depending on the method used to
prepare them
•
The hydrophilic ends are exposed on the outside
and inside of the vesicle, while the hydrophobic chains face each other within the bilayer
Methods of preparation
- Ether
injection method - Film
hydration method - Reverse
phase evaporation - The
“Bubble” method - Micro
fluidization - Sonication
1. Ether injection method
• In
this method a solution of niosomal ingredients in ether is slowly injected into an aqueous medium at
high temperature
• A
mixture of surfactant and cholesterol (150 μmol) is dissolved in ether (20 ml)
• Injected
into an aqueous phase (4 ml) using a 14- gauge
needle syringe at the rate of approximately 0.25ml/min
• The
aqueous phase is preheated to 600C during the injection of the ether solution
• This
causes evaporation of ether leading to the formation of single layered vesicles
• The
particle size of niosomes formed can range b/w 50μm and 1000μm
Advantage
• Niosomes
prepared by ether injection method have better
entrapment efficiency than those prepared by the film or sonication
Disadvantage
• Small
amount of residual ether frequently
remains in the final product and is
difficult to remove
2. Film hydration method
•
Vesicle-forming agents such as the surfactant
and cholesterol are dissolved in a volatile organic solvent such as diethyl ether, chloroform, or methanol in
a round bottom flask
•
The organic solvent is evaporated under reduced pressure using a rotary evaporator
•
A thin film of solid mixture remains deposited
on the walls of the flask
•
The dried surfactant layer is rehydrated with
the aqueous phase at normal temperature
with gentle agitation to yield
unilamellar niosomes or smaller niosomes using sonication, technique
3. Reverse phase evaporation
technique
•
In this method, cholesterol and surfactant (1:1
ratio) are dissolved in a mixture of
ether and chloroform
•
An aqueous phase containing the drug to be loaded
is added to this
•
Mixture is sonicated at 40C- 50C
until a clear gel is formed
•
Phosphate buffered saline (PBS) is added to it Sonicated
•
The temperature is raised to 400C and
the organic phase is removed under
reduced pressure
•
A viscous niosome suspension is obtained
•
Diluted with PBS and heated on a water bath at
600C for 10min to yield
niosomes
4. The Bubble method
•
This method allows the preparation of niosomes without the use of organic solvent
•
The niosomes are prepared in a bubbling unit,
which consists of a round bottom flask with three necks
•
The flask is positioned in a water temperature
•
In the first neck water – cooled reflux is
positioned
•
In the second neck thermometer is fixed
•
The third neck is used to bubble nitrogen gas
into the mixture
•
A dispersion of cholesterol and surfactant in a
buffer (pH 7.4) is taken in the flask
and maintained at 700C
•
The dispersion is then mixed with shear
homogenizer
•
Nitrogen gas is immediately bubbled into it at 700C
to yield niosomes
5. Sonication
•
The aqueous phase is added into the mixture of surfactant and cholesterol in a scintillation
vial
•
Homogenized using a sonic probe
•
The resultant vesicles are of small unilamellar (SUV)
type niosomes
•
The SUV type niosomes are larger than SUV
liposomes
6. Micro fluidization
•
This is a recent technique to prepare small MLVS
•
A
microfludizer is used to pump the fluid at a very high pressure (10,000 psi) through a 5 mm screen
•
It is then forced along defined micro channels,
which direct two streams of fluid to
collide together at right angles, there
by affecting a very efficient transfer of energy
•
The lipids/surfactants can be introduced fluidizer
•
The fluid collected can be recycled until vesicles
are obtained
Separation of
free/unentrapped drug
Dialysis
The aqueous niosomal dispersion is dialyzed in a dialysis
tubing against phosphate buffer or normal saline or glucose solution.
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.
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
Evaluation of niosomes
1. Entrappment efficiency
Entrapment efficiency = Amount entrapped / Total
amount added x 10
2. Vesicle Size
Laser Light Scattering method
3. Particle size analysis
Scanning Electron Microscopy (SEM)
4. Bilayer formation
Polarised Light Microscope
5. Number of lamellae
Nuclear Magnetic Resonance (NMR) spectroscopy
6.In vitro Release Study
7. In vivo Release Study
Scanning Electron Microscopy
Polarised Light Microscope
Applications
•
Anti-neoplastic treatment
•
Treatment of Leishmaniasis
•
Delivery of peptide drugs
•
Used in studying immune response
•
Niosomes as carriers for haemoglobin
•
Transdermal drug delivery systems
Summary
- Niosomes
are vesicular systems in which the medication is encapsulated in a vesicle
composed of a bilayer of non-ionic
surface active agents
2. The
methods of preparation include Ether injection method, Film hydration method,
Reverse phase evaporation, The “Bubble”
method, Micro fluidization, Sonication
3. Niosomes
can be characterized for Entrapment efficiency, Vesicle Size, Particle size, Bilayer
formation, Number of lamellae, In vitro
and In vivo release study
