3. NIOSOMES-NOVEL DRUG DELIVERY
SYSTEMS
The concept of targeted drug delivery is designed for
attempting to concentrate the drug in the tissues of target
while reducing the relative concentration of the drug in the
remaining tissues. As a result, drug is localised on the
targeted site. Hence, surrounding tissues are not affected by
the drug. In addition, loss of drug does not happen due to
localisation of drug, leading to get maximum efficacy of the
medication.
Different carriers have been used for targeting of drug, such
as immunoglobulin, serum proteins, synthetic polymers,
liposomes, microspheres, erythrocytes and niosomes.
4. Introduction
Niosomes are one of the best among these
carriers. A Niosome is a non-ionic surfactant-
based Vesicle. Niosomes are formed mostly by
non-ionic surfactant and cholesterol
incorporation as an excipient. Other
excipients can also be used.
Niosomes have more penetrating capability
than the previous preparations of emulsions.
They are structurally similar to liposomes in
having a bilayer, however, the materials used
to prepare niosomes make them more stable.
It can entrap both hydrophilic and lipophilic
drugs, either in an aqueous layer or organic
layer.
5. Definition
Niosomes are a novel drug delivery system, in which
the medication is encapsulated in a vesicle. The vesicle is
composed of a bilayer of non-ionic surface active agents and hence
the name niosomes.
The niosomes are very small, and microscopic in
size. Their size lies in nanometric scale.
(Or)
Niosomes are synthetic microscopic vesicles consists of an
aqueous core enclosed in a bilayer consisting of cholesterol and
one or more non ionic surfactants.
6. Advantages of Niosomes
Niosomes are osmotically active, chemically stable and have long
storage time compared to liposomes
They are biodegradable and non-immunogenic
They can improve the therapeutic performance of the drug
molecules by protecting the drug from biological environment,
resulting in better availability and controlled drug delivery by
restricting the drug effects to target cells in targeted carriers and
delaying clearance from the circulation in sustained drug delivery
7. Advantages Continution :
They can entrap lipophilic drugs into vesicular bilayer
membranes and hydrophilic drugs in aqueous compartments
They have high compatibility with biological systems and low
toxicity because of their non-ionic nature
Access to raw materials is convenient
Their surface formation and modification is very easy because
of the functional groups on their hydrophilic heads
9. Compositions Of Niosomes:
• The two major components used for the preparation of niosomes are,
• 1. Cholesterol 2. Nonionic surfactants
1. Cholesterol
• Cholesterol is used to provide rigidity and proper shape, conformation to
the niosomes preparations.
2. Nonionic surfactants
• The role surfactants play a major role in the formation of niosomes.
• The following non-ionic surfactants are generally used for the preparation
of niosomes. E.g. Spans (span 60, 40, 20, 85, 80) Tweens (tween 20, 40, 60,
80).
• The non ionic surfactants possess a hydrophilic head and a hydrophobic
tail.
10. Methods Of Preparation
Niosomes Can Be Prepared By Various Methods, Including:
1. Ether Injection Method (EIM)
2. Hand Shaking Method (HSM)
3. Reverse Phase Evaporation Method (REV)
4. Trans Membrane Ph Gradient
5. The "Bubble" Method
6. Micro fluidization Method
7. Formation Of Niosomes From Pro-niosomes ( Proniosome Technology)
(PT)
8. Thin-film Hydration Method (TFH)
9. Heating Method (HM)
10. Freeze And Thaw Method (FAT)
11. Dehydration Rehydration Method (DRM)
11. 1.Ether Injection Method
This method provides a
means of making niosomes by slowly
introducing a solution of surfactant
dissolved in diethyl ether into warm water
maintained at 60°C. The surfactant
mixture in ether is injected through 14-
gauge needle into an aqueous solution of
material. Vaporization of ether leads to
formation of single layered vesicles.
Depending upon the conditions used the
diameter of the vesicle range from 50 to
1000 nm.
Preparation steps
1. Surfactant is dissolved in diethyl ether
2. Then injected in warm water maintained
at 60oC through a 14 gauze needle
3. Ether is vaporized to form single layered
niosomes.
12. 2.Sonication Method
In this method an aliquot of drug
solution in buffer is added to the
surfactant/cholesterol mixture in a 10-ml
glass vial. The mixture is probe sonicated
at 60°C for 3 minutes using a sonicator
with a titanium probe to yield niosomes.
Preparation steps
1. Drug in buffer +
surfactant/cholesterol in 10 ml
2. Above mixture is sonicated for 3
mints at 60oC using titanium probe
yielding niosomes.
13. 3.Hand Shaking Method
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, a thin layer of solid
mixture deposited on the wall of the flask. The dried layer is hydrated
with aqueous phase containing drug at normal temperature with
gentle agitation.
14. Preparationsteps:
1. Surfactant + cholesterol + solvent
2. Remove organic solvent at Room temperature
3. Thin layer formed on the Walls of flask
4. Film can be rehydrated to form multilamellar Niosomes.
4.Micro fluidization Method
Micro fluidization is a recent technique used to prepare
unilamellar vesicles of defined size distribution. This method is base
evaporator, leaving on submerged jet principle in which two fluidized
streams interact at ultra high velocities, in precisely defined micro channels
within the interaction chamber. The result is a greater uniformity, smaller
size and better reproducibility of niosomes formed.
Preparationsteps
1. Two ultra high speed jets inside interaction chamber
2. Impingement of thin layer of Liquid in micro channels
3. Formation of uniform Niosomes.
15. 5.Multiple membraneextrusion method
Mixture of surfactant, cholesterol
and diacetyl phosphate in chloroform is
made into thin film by evaporation. The
film is hydrated with aqueous drug
polycarbonate membranes, solution and
the resultant suspension extruded through
which are placed in series for upto 8
passages.
It is a good method for controlling
niosome size.
16. 6. Reverse Phase Evaporation Technique (REV):
Cholesterol and surfactant (1:1)
are dissolved in a mixture of ether and
chloroform. 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 ,after the
addition of a small amount of phosphate
buffered saline (PBS). The organic phase
is removed at 40°C under low pressure.
The resulting viscous niosome suspension
is diluted with PBS and heated on a water
bath at 60°C for 10 min to yield niosomes.
17. 7.Trans-membrane PH gradient drug uptake
process (remote Loading)
Surfactant and cholesterol are dissolved in chloroform. The
solvent is then evaporated under reduced pressure to obtain a thin film
on the wall of the round-bottom flask. The film is hydrated with 300 ml
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 multi lamellar vesicles.
18. Preparation steps
Surfactant + cholesterol in chloroform
↓
Solvent is evaporated under reduced pressure
↓
Thin film is deposited on the walls of RBF
↓
Hydrated with citric acid by vortex mixing
↓
3 cycles of freezing and thawing then sonication
↓
Addition of aqueous drug solution and vortoxing
↓
pH raised to 7.0-7.2 by 1M disodium phosphate
↓
19. RBF as bubbling unit with three necks
in water bath
↓
Reflux, thermometer and nitrogen
supply by three necks
↓
Cholesterol + surfactant dispersed in
buffer pH 7.4 at 70oC
↓
Above dispersion is homogenized for 15
sec and then bubbled with nitrogen
at 70oc
↓
To get niosomes.
20. 8.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 is
positioned in the first and second neck and nitrogen supply
through the third neck. Cholesterol and surfactant are
dispersed together in this buffer (PH 7.4) at 70°C, the
dispersion mixed for 15 seconds with high shear
homogenizer and immediately afterwards “bubbled” at
70°C using nitrogen gas.
21. VARIOUS TYPES OF NIOSOMEs
Based on the vesicle size, niosomes can be
divided into three groups.
These are
1. Small unilamellar vesicles (SUV, size=0.025-0.05
μm)
2. Multilamellar vesicles (MLV, size=>0.05 μm), and
3. large unilamellar vesicles (LUV, size=>0.10 μm).
22. EVALUATIONTESTS:
Niosomal drugloadingand encapsulation efficiency
The niosomal aqueous suspension was ultra centrifuged,
supernatant was removed and sediment was washed twice with
distilled water in order to remove the absorbed drug.
Entrapment efficiency(%) = Amount of drug in niosomes
/amount of drug used×100
Niosomal drug delivery
The simplest method to deteremine invitro release kinetics of the
loaded drug is by incubating a known quantity of drug loaded niosomes
in a buffer of suitable PH at 37ͦ c with continous stirring withdrawing a
samples periodically and analyses the amount if drug by suitable
analytical techniques dialysis bags or dialysis membranes are commonly
used to minimize interference.
23. size shape morphology:
Electron microscopy and light scattering used for
morphological studies of vesicles.
Gel chromatography used for size distribution
vesicle surface charge
Determined by measurement of electrophoretic
motiliy of vesicles and expressed in terms of zeta
potential.
24. Stability study
All niosomal formulations were subjected to stability studies by
storing at 4 ͦC 25 4 ͦC and 37C in thermostatic oven for the period of
three months
After one month drug content of all the formulations were checked by
method discussed previously in entrapped efficiency parameter.
In vitro release studies of selected formulations were also carried out.
Entrapment efficiency :
Entrapment efficiency of the niosomal dispersion in can be done by
separating the unentrapped drug by dialysis/centrifugation or gel
filtration and the drug remained entrapped in niosomes is determined
by complete vesicle disruption using 50% n-propanol or 0.1% Triton
X-100 and analyzing the resultant solution by appropriate assay
method for the drug. Where,
Percentage entrapment = Total drug –Diffused drug/Total drug ×100
25. Applications
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.
The niosomal vesicles are taken up by reticulo-endothelial system.
Such localised drug accumulation is used in treatment of diseases,
such as leishmaniasis.
It has good control over the release rate of drug, particularly for
treating brain malignant cancer.
26. Niosomes have been used for studying the nature of the immune response
produced by antigens.
Niosomes can be used as a carrier for haemoglobin
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.
Niosomes a novel drug delivery system that are finding other application in:
• Gene Delivery
• Delivery of Peptide Drugs
• Carriers For Haemoglobin
• It is used in Ophthalmic drug delivery
• Transdermal Drug Delivery Systems
• Cosmetics
27. Marketed products
Lancôme has come out with a
variety of anti-ageing products
which are based on niosomes
Formulations.
L’Oreal is also conducting research
on anti-ageing cosmetic products.
Niosomes Preparation in the Market
is – Lancôme
28. Conclusion
The concept of incorporating the drug into niosomes for
a better targeting of the drug at appropriate tissue
destination.
They presents a structure similar to liposome and
hence they can represent alternative vesicular systems
with respect to liposomes.
Niosomes are thoughts to be better candidates drug
delivery as compared to liposomes due to various
factors like cost, stability etc. …
29. References
1. Khandare JN., Madhavi G., Tamhankar BM., Niosomes Novel Drug
Delivery System. The Eastern Pharmacist. 1994, 37: 61-64.
2. Baillie AJ., Florence AT., Hume LR., Muirhead GT., Rogerson A., The
preparation and properties of niosomes non-ionic surfactant vesicles. J.
Pharm. Pharmacol. 1985, 37: 863- 868.
3. http//en.wikipedia.org/wiki/Niosomes, structure of niosomes.
4. Rogerson A., Cummings J., Willmott N., Florence AT., The distribution of
doxorubicin in mice following administration in niosomes. J. Pharm.
Pharmacol. 1988, 40: 337-342.
5. Biju SS., Talegaonkar S., Misra PR., Khar RK., Vesicular systems: An
overview. Indian J. Pharm. Sci. 2006, 68: 141-153.
6.Malhotra M., Jain N.K., Niosomes as Drug Carriers. Indian Drugs. 1994,
31(3): 81-866.