3. 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, and microscopic in size that lies in the
nanometric scale. Although structurally similar to liposomes,
they offer several advantages over them.
Niosomes have recently been shown to greatly increase
transdermal drug delivery and also in targeted drug delivery.
4. Used for a variety of drugs : accommodate hydrophilic,
lipophilic as well as amphiphilic moieties.
Act as a depot to release the drug slowly and offer a controlled
release .
Osmotically active and stable.
Increase the stability of the entrapped drug.
Handling and storage of surfactants do not require any special
conditions
Enhance the skin penetration of drugs
5. Niosomes are microscopic lamellar structures, which are
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 areexposed 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 space
enclosed in the vesicle, while hydrophobic drugs are
embedded within the bilayer itself.
9. In both basic unit of assembly is Amphiphiles, but they
phospholipids in liposomes and nonionic surfactants in
niosomes.
Both can entrap hydrophilic and lipophilic drugs.
Both have same physical properties but differ in their chemical
composition.
Niosomes has higher chemical stability than liposomes.
Niosomes made of uncharged single chain
surfactant molecules
Liposomes made of neutral or charged double
chain phospholipids.
10. Function
Increase the bioavailability
Decrease the clearence
Used for targeted drug delivery
Properties depends on both composition of bilayer and
method of preparation
11. o Ester bonds of phospholipids are easily hydrolyzed, this can
lead to phosphoryl migration at low PH.
o Peroxidation of unsaturated phospholipids.
o As liposomes have purified phospholipids they are to be
stored and handled at inert(N2) atmospheres where as
Niosomes are are made of non ionic surfactants and are easy
to handle and store.
o Phospholipid raw materials are naturally occurring substances
and as such require extensive purification thus making them
costly
12. 1.Bola-Surfactant containing Niosomes:
Niosomes made of alpha,omega-hexadecyl-bis-(1-aza-18-
crown-6) (Bola-surfactant)-Span 80-cholesterol (2:3:1 molar
ratio) are named as Bola-Surfactant containing Niosomes.
2. Proniosomes:
A dry product which may be hydrated immediately before
use to yield aqueous Niosome dispersions. These
‘proniosomes’ minimize problems of Niosome physical
stability such as aggregation, fusion and leaking, and provide
additional convenience in transportation, distribution,
storage, and dosing.
15. Nature of non-ionic surfactant
Type of surfactant influences encapsulation efficiency, toxicity,
and stability of niosomes
SURFACTANT
Hydrophobic tail Hydrophilic head
Linked via ether , amide
or ester bonds
Consist of one or two alkyl or
perfluroroalkyl groups or in some
cases a single steriodal group.
16. • The alkyl group chain length is usually from C12-C18
• Uchegbu et al reported that Span surfactants with HLB values
between 4 and 8 were found to be compatible with vesicle
formation
• The water soluble detergent polysorbate 20 (HLB value 16.7)
also forms niosomes with cholesterol
• Polyglycerol monoalkyl ethers and polyoxylate analogues are
the most widely used single-chain surfactants
17. Membrane additives
Cholesterol, a natural steriod, is the most commonly used
membrane additive
Usually incorporated in 1:1 molar ratio
Prevent vesicle aggregation by the inclusion of molecules that
stabilize the system against the formation of aggregates by
repulsive steric or electrostatic effects
Leads to the transition from the gel state to liquid phase in
niosomes systems
As the result, niosomes become less leaky
Cholesterol
Dicetyl phosphate provides negative charge to vesicles
It is used to prevent aggregation of hexadecyl diglycerol
ether (C16G2) niosomes
Stearic acid is used in the preparation of cationic
niosomes
Dicetyl phosphate and
Stearic acid
18. Surfactant and lipid levels
• 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
Hydration temperature
• The hydrating temperatures used to make niosomes should
usually be above the gel to liquid phase transition
temperature of the system
20. Ether injection method
• Slow injection of an ether solution of niosomal ingredients
into an aqueous medium at high temperature
• A mixture of surfactant and cholesterol (150 μmol) is
dissolved in ether (20 ml) and injected into an aqueous phase
(4 ml) using a 14- gauge needle syringe
• Temperature of the system is maintained at 60oC during the
process
• Niosomes in the form of large unilamellar vesicles (LUV) are
formed
21. Film method
• The mixture of surfactant and cholesterol is dissolved in an
organic solvent (e.g. diethyl ether, chloroform, etc.) in a
round-bottomed flask
• The organic solvent is removed by low pressure/vacuum at
room temperature
• The resultant dry surfactant film is hydrated by agitation at
50-60oC
• Multilamellar vesicles (MLV) are formed
22. 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
• It is possible to obtain SUV niosomes by sonication of MLV
type vesicles
23. Reverse phase evaporation
• Surface-active agents are dissolved in chlorofom, and 0.25
volume of phosphate saline buffer (PBS) is emulsified to get
w/o emulsion
• The mixture is sonicated and subsequently chloroform is
evaporated under reduced pressure
• The surfactant first forms a gel and then hydrates to form
niosomal vesicles
• The vesicles formed are unilamellar and 0.5 μ in diameter
24. The “Bubble” method
It is novel technique for the one step preparation of liposomes
and niosomes without the use of organic solvents
The bubbling unit consists of round-bottomed flask with three
necks positioned in water bath to control the temperature
Water-cooled reflux and thermometer are positioned in the
first and second neck and nitrogen supply through the third
neck
Cholesterol and surfactant are dispersed together in the
buffer (pH 7.4) at 70°C, the dispersion mixed for 15 secs with
high shear homogenizer and immediately afterwards
“bubbled” at 70°C using nitrogen gas
25. 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 pm screen
It is then forced along defined micro channels, which direct
two streams of fluid to collide together at right angles,
thereby affecting a very efficient transfer of energy
The lipids/surfactants can be introduced into the fluidizer
The fluid collected can be recycled until spherical vesicles are
obtained
Uniform and small sized vesicles are obtained
29. Entrapment efficiency
Depend on the method of preparation
Niosomes prepared by ether injection method have better
entrapment efficiency than those prepared by the film or
sonication
Addition of cholesterol to non-ionic surfactants with single- or
dialkyl-chain significantly alters the entrapment efficiency
Surfactants of glycerol type lead to reduction in entrapment
capacity as the amount of cholesterol increases
Niosomes in the form of liquid crystals possess better
entrapment efficiency than gel type vesicles
30. Entrapment efficiency (EF) = (Amount entrapped total
amount) x100
Niosomes, similar to liposomes, assume spherical shape and
so their diameter can be determined using light microscopy,
photon correlation microscopy and freeze fracture electron
microscopy.
Freeze thawing (keeping vesicles suspension at –20°C for 24
hrs and then heating to ambient temperature) of niosomes
increases the vesicle diameter, which might be attributed to
fusion of vesicles during the cycle.
31. In-vitro release :
A method of in-vitro release rate study includes the use of
dialysis tubing. A dialysis sac is washed and soaked in distilled
water. The vesicle suspension is pipetted into a bag made up
of the tubing and sealed. The bag containing the vesicles is
placed in 200 ml of buffer solution in a 250 ml beaker with
constant shaking at 25°C or 37°C. At various time intervals, the
buffer is analyzed for the drug content by an appropriate
assay methodof vesicles during the cycle.
32. Vesicles are stabilised based upon formation of following forces:
van der Waals forces among surfactant molecules
Electrostatic repulsive forces are formed among vesicles upon
addition of charged surfactants to the double layer, enhancing
the stability of the system
33. Niosomes in the form of liquid crystal and gel can remain stable
at both room temperature and 4oC for 2 months
Recommended temperature of storage 4oC
Ideally niosomes should be stored dry for reconstitution
The factors which affect the stability of niosomes:
Type of surfactant
Nature of encapsulated drug
Storage temperature
Detergents
Use of membrane spanning lipids
Inclusion of charged molecule
35. Transdermal Applications
Slow penetration of drug through skin is the major drawback of
transdermal route of delivery. An increase in the penetration rate has
been achieved by transdermal delivery of drug incorporated in niosomes.
has studied the topical delivery of erythromycin from various
formulations including niosomes or hairless mouse.
parenteral Applications
Niosomes in sub-micron size are used for parenteral administration
Niosomal vesicles upto 10 μm are administered via i.p. or i.m.
36. Radiopharmaceuticals
First application of niosomes as radiopharmaceuticals demonstrated by
Erdogan et al. in 1996.
• Delivery of peptide drugs
Oral delivery of 9-desglycinamide, 8-arginine vasopressin entrapped in
niosomes increase stability of peptide significantly.
37. Ophthalmic Drug Delivery
Saettone et al. (1996) reported on the biological evaluation of a
niosomal Cyclopentolate delivery system for opthalmic delivery
Polysorbate 20 and cholesterol were used for niosomes formulation
Optimum pH for peak permation values was pH 5.5, permeatiom
decreased at pH 7.4
But in vivo data showed no such dependent on pH
Niosomes> 10 μm are suitable for drug administration to eye
38. Combination of PEG and glucose conjugates on the surface of niosomes
significantly improved tumor targeting of an encapsulated paramagnetic
agent 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.
A research article was published that Acyclovir entrapped niosomes were
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
39. The concept of incorporating the drug into liposomes or
niosomes for a better targeting of the drug at appropriate tissue
destination is widely accepted by researchers and
academicians.
Niosomes represent a promising drug delivery module.
Niosomes are thoughts to be better candidates drug delivery
as compared to liposomes due to various factors like cost,
stability etc .
Various type of drug deliveries can be possible using niosomes
like targeting, ophthalmic, topical, parenteral, etc.
Niosomes can also serve better aid in diagnostic imaging and
vaccine adjuvant in pharmaceutical industry.
40. 1. Malhotra M and Jain NK. Niosomes as Drug Carriers. Indian
Drugs 31 (3), 1994, 81-86.
2. Handjani-Vila RM., Ribier A, Rondot B and Vanlerberghie G.
Dispersions of lamellar phases of non-ionic lipids in cosmetic
products. International Journal of Cosmetic Science 1 (5),
1979, 303-314.
3. Baillie AJ, Florence AT, Hume LR, Rogerson A, and Muirhead GT
,The preparation and properties of niosomes-non-ionic
surfactant vesicles. J. Pharm Pharmacol. 37(12), 1985, 863–
868.
