Chapter on Niosome

1. 1
By:Rajesh L. Dumpala
(B.Pharm, M. Pharm.) PhD. ( Pursuing)
Research Scientist,
Alembic Research Centre. Vadodara
E.Mail:-rdumpala64@gmail.com

2. Contents
1.Introduction
2.General characteristics of Niosomes
3.Compare and Contrast of Niosomes and Liposomes
4.Methods of Preparation
5.Characterization of Niosomes
6.Therapeutic Applications
7.Future Prospects
8.References

3. • Development of new drug , improving safety and efficacy of existing
drugs is difficult, expensive and time consuming
• At present, no available drug delivery system behaves ideally
achieving all the lofty goals
• Encapsulation of the drug in vesicular structures is one of the
promising system
• such as liposomes, niosomes, transfersomes, and pharmacosomes etc
• It delivers drug directly to the site of action, leading to reduction of
drug toxicity with no adverse effects

4. •Vesicular drug delivery reduces the cost of therapy by improving
bioavailability of medication and also solves the problems of drug
insolubility, instability and rapid degradation
•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 and hence the name niosomes
•The niosomes are very small, and microscopic in size. Their size lies in
the nanometric scale

5. • Niosomes are synthetic microscopic vesicles consisting of an
aqueous core enclosed in a bi layer consisting of cholesterol
and one or more nonionic surfactants
• Vesicles are prepared from self assembly of hydrated non ionic
surfactants molecules

6. Structure of Niosomes
• Niosomes are microscopic lamellar structures
• Basic structural components are
 Non ionic surfactant
 Cholesterol
 Charge inducing molecule such as Dicetyl phosphate
• A number of non- ionic surfactants used are
polyglycerol alkyl ether, glucosyl dialkyl ethers, crown ethers,
ester linked surfactants, polyoxyethylene alkyl ether and a series
of spans and tweens

8. •The niosome is made of a surfactant bilayer with its hydrophilic ends
exposed on the outside and inside of the vesicle, while the hydrophobic
chains face each other within the bilayer
•The geometry of vesicles to be formed from surfactant is affected by its
structure, which is related to critical packing parameter
 CPP(Critical Packing Parameter) = v/Ic * a0
where v = hydrophobic group volume
Ic = the critcal hydrophobic group length
a0 = the area of hydrophilic head group

9. Factors affecting vesicles size, entrapment efficiency and
release characteristics
•Drug
•Amount of surfactant
•Cholesterol content and charge
•Method of preparation
•Resistance to osmotic stress

10. General Characteristics of Niosome
• Biocompatible, biodegradable, non-toxic, non immunogenic and
non-carcinogenic
• The ability of nonionic surfactant to form bilayer vesicles is
dependant on the HLB value of the surfactant, the chemical
structure of the components and the critical packing parameter
• Niosomes can be characterized by their size distribution studies
• High resistance to hydrolytic degradation
• The properties of niosome depends both on composition of the
bilayer & on method of their production

11. Advantages of Niosome
• The vesicle suspension is water–based vehicle, offers high patient
compliance
• The vesicles may act as a depot, releasing the drug in a controllable
manner
• They are osmotically active and stable
• Handling and storage of surfactants requires no special conditions.
• They improve oral bioavailability of poorly absorbed drugs and
enhance skin penetration of drugs
• Niosome improves therapeutic performance of drug molecules

12. Disadvantages of Niosome
• Aqueous suspension of niosome may exhibit fusion, aggregation
leaching or hydrolysis of entrapped drug, thus limiting the shelf
life of niosome dispersion.
• Time consuming
• Requires specialized equipment
• Inefficient drug loading

13. Contrast of Niosomes Vs liposomes
Niosome Liposome
1. Less Expensive 1. More expensive
2. Chemically Stable 2. Chemically unstable
3. Niosomes are prepared
from uncharged single-
chain surfactant
3. liposomes are prepared
from double-chain
phospholipids
4. They do not require
special storage and
handling
4. They require special
storage, handling &
purity of natural
phospholipid is variable.
5. Non ionic drugs carriers
are safer
5. The ionic drugs carriers
are relatively toxic &
unsuitable

14. Comparision of niosomes and liposomes
• Properties of both depends on composition of bilayer and
method of production
• Increase in surfactant lipophilicity, increases entrapment
efficiency
• Increase in cholesterol concentration, decreases in
entrapment efficiency
• Lipophilic surfactant forms mean size reduction

15. Methods of Preparation
1. Ether Injection
2. Hand Shaking Method
3. The “Bubble” Method
4. Reverse Phase Evaporation
5. Sonication

16. 6. Micro Fluidization
7. Trans Membrane pH Gradient Drug Uptake Process
(remote Loading)
8. Formation of Niosomes From Proniosomes

17. • Hydration of mixture of surfactant/lipid at elevated
temperature
• Sizing of niosomes
• Removal of unentrapped material from vesicles

18. Cholesterol + Non ionic surfectant
Dissolve in organic solvent
Solution in organic solvent
Drying
Thin film
Dispersion (Hydration)
Niosome suspension

19. A.Ether injection method
• This method is based on slow injection of surfactant : cholesterol
solution in ether through 14 gauge needle into a preheated aqueous
phase maintained at 600C
• Vaporization of ether resulting into a formation of ether gradient at
ether-water interface which leads to formation of single layered
vesicles
• Depending upon the conditions used, the diameter of the vesicle range
from 50 to 1000 nm

20. B. Hand shaking method
(Thin film hydration technique)
• Surfactant and cholesterol are dissolved in a volatile organic solvent
(diethyl ether, chloroform or methanol) in a round bottom flask
• The organic solvent is removed under vaccum at room temperature
using rotary evaporator leaving a thin layer of solid mixture
deposited on the wall of the flask
• The dried surfactant film can be rehydrated with aqueous phase at
temperature slightly above the phase tansition temperature of the
surfactant used, with gentle agitation
• This process forms large multilamellar niosomes

21. C. 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-bottom 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

22. D. 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

23. E. Sonication
•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.
•The resultant vesicles are of small unilamellar type niosomes.
F. Extrusion method
• Niosomes can be prepared by extrusion method using nucleopore filter
of pore size 100nm.
•Vesicles of mean size diameter 100-150nm can be prepared.
•Good method of controlling niosome size.

24. G. Trans membrane pH gradient (inside acidic) Drug
Uptake Process (remote Loading)
•Surfactant and cholesterol are dissolved in chloroform
• The solvent is then evaporated under reduced pressure to get a thin film
on the wall of the round bottom flask
•The film is hydrated with 300 mM citric acid (pH 4.0) by vortex mixing.
•The multilamellar vesicles are frozen and thawed 3 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 give niosomes

25. H.Formation of niosomes from proniosomes
•Another method of producing niosomes is to coat a water-soluble carrier
such as sorbitol with surfactant
• The result of the coating process is a dry formulation. In which each
water-soluble particle is covered with a thin film of dry surfactant. This
preparation is termed “Proniosomes”
•The niosomes are formed by the addition of aqueous phase at T > Tm
and brief agitation
T = Temperature.
Tm = mean phase transition temperature

26. Separation of unentrapped drugs
The removal of unentrapped solute from the vesicles can be
accomplished by various techniques, which include
1. Gel Filtration
2. Dialysis
3. Centrifugation

27.  Physical characterization
 Chemical characterization
 Biological characterization

28. Physical characterization
Sr no. Parameters Analytical
methods/Instruments
1. Vesicles shape & surface
morphology
Transmission electron
microscopy,
Freeze-fracture electron
microscopy
2. Mean vesicle size and size
distribution
(submicron and micron range)
Dynamic light scattering,
zetasizer,
Photon correlation
spectroscopy,
laser light scattering, gel
permeation and gel
exclusion
3. Surface charge Free-flow electrophoresis

29. 4. Phase behavior Freeze-fracture electron
microscopy, Differential
scanning colorimetery
5. Electrical surface potential and
surface pH
Zeta potential
measurements & pH
sensitive probes
6. Entrappment efficiency Amount entrapped/total
amount added*100

30. Sr no Parameters Analytical
methods/Instruments
1. Cholesterol concentration Cholesterol oxidase
assay and HPLC
2. Cholesterol auto-oxidation HPLC and TLC
3. Osmolarity Osmometer

31.  Biological characterization
Sr No. Parameters Analytical
methods/Instruments
1. Sterility Aerobic or anaerobic cultures
2. Pyrogenicity Limulus Amebocyte Lysate
(LAL) test
3. Animal toxicity Monitoring survival rates,
histology and pathology

32. 1. Intravenous Route Ipromide, Vincristine,Indomethacin, Colchicines,
Rifampicin, Transferrin, Zidovudine, Cisplantin,
amarogentin, Daunorubicin, AmphotericinB.
2. Transdermal Route Flurbiprofen, Piroxicam, Levonorgestrol,
Nimeluside, Estradiol, Ketoconazole, Enoxacin,
DNA loaded noisome, Cyclosporine,
Erythromycin, α interferon.
3. Oral Route Vaccine, Polysaccharide Coated noisome, Cipro
floxacin, Insulin.
4. Oncology Route Methotrexate, Doxorubicin, adriamycin.
5. Ocular Route Timolol, cyclopentolate
6. Nasal Route Sumatriptan, Influenza
7.Immunological Adjuvant Bovine serum albumin, Hemoglobin
8. For treatment of Leishmaniasis Stilbogluconat
Therapeutic Application

33. APPLICATIONS OF NIOSOMES
•Drug targetting :
•Anti neoplastic treatment :
Doxorubicin, Methotrexates, Bleomycin, Vincristine
• Delivery of Peptide Drugs:
vasopressin derivative.
•Niosomes as Carriers for Haemoglobin :
• Transdermal Drug Delivery Systems Utilizing Niosomes :
antibiotics to treat acne
• Sustained Release : drugs with low therapeutic index and low
water solubility .
•Localized Drug Action : in cancer chemotherapy and anti-
leishmanial therapy.

34. • Niosomes represent a promising drug delivery
module.
• There is lot of scope to encapsulate toxic anti-cancer drugs, anti
infective drugs, anti AIDS drugs, anti-inflammatory drugs, anti viral
drugs, etc. in niosomes and to use them as promising drug carriers to
achieve better bioavailability and targeting properties and for reducing
the toxicity and side effects of the drugs.
• The ionic drugs carriers are relatively toxic and unsuitable whereas
niosomal carriers are safer.
Future Prospects

35. • In addition, handling and storage of niosomes require no special
conditions.
• Vesicular drug carriers like niosomes can be transported by
microphages which are known to infiltrate tumour cells.
• It may be possible to take advantage of these activated macrophage
system in delivering the anti tumour agents within vesicles more
quantitatively to tumour sites.

36. REFERENCES
1. Sanjay K. Jain and N.K. Jain
Controlled and novel drug delivery system
2. Dr. Rakesh S. Patel niosomes as a unique drug delivery system,
www.pharmainfo.net
3. Mithal, B. M., A text book of pharmaceutical formulation, 6th
Edn., vallabh prakashan, 6, 306-307
4. International journal of pharmaceutical Science and
Nanotechnology volume 1,issue 1, April-June 2008

37. Thank You