NIOSOMES , GENERAL CHARACTERISTICS OF NIOSOME , TYPES OF NIOSOMES , OTHERS TYPES OF NIOSOMES , NIOSOMES VS LIPOSOMES , COMPONENTS OF NIOSOMES , Non-ionic surfactant , Cholesterol , Charge inducing molecule , METHOD OF PREPARATION , preparation of small unilamellar vesicles , Sonication , Micro fluidization , preparation of large unilamellar vesicles , Reverse Phase Evaporation , Ether Injection , preparation of Multilamellar vesicles , Hand shaking method , Trans membrane pH gradient drug uptake process (remote loading) , Miscellaneous method :Multiple membrane extrusion method , The “Bubble” Method , Formation of Niosomes From Proniosomes , SEPARATION OF UNENTRAPPED DRUGS , Gel Filtration , Dialysis , Centrifugation , FACTORS AFFECTING THE PHYSICOCHEMICAL PROPERTIES OF NIOSOMES , Membrane Additives , Temperature of Hydration , PROPERTIES OF DRUGS , AMOUNT AND TYPE OF SURFACTANT Structure of Surfactants , Resistance to Osmotic Stress , Characterization of niosomes ,Therapeutic applications of Niosomes , For Controlled Release of Drugs , To Improve the Stability and Physical Properties of the Drugs , For Targeting and Retention of Drug in Blood Circulation , Proniosomes , Aspasomes , Vesicles in Water and Oil System (v/w/o) ,Bola - niosomes , Discomes , Deformable niosomes or elastic niosomes , According to the nature of lamellarity ,Small Unilamellar vesicles (SUV) 25 – 500 nm in size.,Large Unilamellar vesicles (LUV) 0.1 – 1μm in size , Multilamellar vesicles (MLV) 1-5 μm in size , According to the size:Small Niosomes (100 nm – 200 nm) , Large Niosomes (800 nm – 900 nm),Big Niosomes (2 μm – 4 μm)

1. NIOSOMES
1
Presented by
P.Pavazhaviji
M.Pharm I Year (II Sem)
Dept. of Pharmaceutics
MTPG & RIHS
Puducherry

2. DEFINITION
 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 .
 Niosomes also called as nonionic surfactant vesicles or NSVs .
Nios = non ionic surfactant
Somes = vesicles
2

3. STRUCTURE3

4. GENERAL CHARACTERISTICS OF NIOSOME
 Biodegradable
 Biocompatible
 Non-toxic
 Non-immunogenic
 Non-carcinogenic
 High resistance to hydrolytic degradation
4

5.  According to the nature of lamellarity
1. Small Unilamellar vesicles (SUV) 25 – 500 nm in size.
2. Large Unilamellar vesicles (LUV) 0.1 – 1μm in size
3. Multilamellar vesicles (MLV) 1-5 μm in size.
 According to the size
1. Small Niosomes (100 nm – 200 nm)
2. Large Niosomes (800 nm – 900 nm)
3. Big Niosomes (2 μm – 4 μm)
TYPES OF NIOSOMES
5

6. 6

7. OTHERS TYPES OF NIOSOMES
 Proniosomes
 Aspasomes
 Vesicles in Water and Oil System (v/w/o)
 Bola - niosomes
 Discomes
 Deformable niosomes or elastic niosomes
7

8. ADVANTAGES OF NIOSOMES
 Targeted drug delivery
 Reduction in dose
 Decrease in the side effects
 Both hydrophilic and lipophillic drugs can be encapsulated
 Enhance the skin permeability of drugs
 The surfactants used and also the prepared niosomes are biodegradable,
biocompatible and non-immunogenic
 They are osmotically active and stable
8

9. DISADVANTAGES OF NIOSOME
 Fusion,
 Aggregation,
 Leaching
 Hydrolysis
 Time consuming
 Requires specialized equipment
 Inefficient drug loading
 High production cost
9

10. NIOSOMES VS LIPOSOMES
10

11. COMPONENTS OF NIOSOMES
 Non-ionic surfactant
 Cholesterol
 Charge inducing molecule
11

12. NON-IONIC SURFACTANTS
 The non-ionic surfactants orient themselves in bilayer lattices
where the polar or hydrophilic heads facing hydrophilic region
while the non-polar tails facing each other to form a hydrophobic
region.
12

13. 13

14. CHOLESTEROL
 Cholesterol is a steroid derivative, which is mainly used for the formulation of
niosomes. Although it may not show any role in the formation of bilayer.
 It makes the membrane rigid , increase the entrapment efficiency .
 It prevents the vesicle aggregation by the inclusion of molecules that stabilize the
system against the formation of aggregates by repulsive steric or electrostatic
forces .As a result of this, the niosome becomes less leaky in nature.
14

15. CHARGE INDUCING MOLECULE
 Some charged molecules are added to niosomes to increase
stability of niosomes by electrostatic repulsion which prevents
aggregation and coalescence.
 The negatively charged molecules used are diacetyl
phosphate (DCP) and phosphotidic acid. Similarly,
stearylamine (STR) and stearyl pyridinium chloride are the
well known positively charged molecules used in niosomal
preparations.
 Only 2.5-5 % concentration of charged molecules is tolerable
because high concentration can inhibit the niosome formation.
15

16. METHOD OF PREPARATION:
1) preparation of small unilamellar vesicles
• Sonication
• Micro fluidization
2) preparation of large unilamellar vesicles
• Reverse Phase Evaporation
• Ether Injection
3) preparation of Multilamellar vesicles
• Hand shaking method
• Trans membrane pH gradient drug uptake process (remote
loading)
4) Miscellaneous method :
• Multiple membrane extrusion method
• The “Bubble” Method
• Formation of Niosomes From Proniosomes
16

17. 1) Preparation of small unilamellar vesicles
a) Sonication
Niosomes
sonicated for 3mins at 60°c using
titanium probe
Drug in buffer + surfactant
/cholesterol in 10ml glass vial
17

18. 18

19. b) Micro fluidization
Two ultra high speed jets inside interaction chamber
Impingement of thin layer of liquid in micro channels
Niosomes
High speed impingment & the energy involved
19

20. 2) preparation of large unilamellar vesicles
a) Reverse Phase Evaporation
Surfactant + cholesterol (1:1) in
organic solvent
Drug in aqueous phase
Sonicated at 4-5°c
Add phosphate buffer saline &
sonicate
Viscous niosomes suspension
diluted with PBS
Organic phase is removed at 40°c
Under low pressure
Heated on a water bath at 60°c for 10
mins
Niosomes
20

21. 21

22. b) Ether Injection
Surfactant is dissolved in diethly
ether
Then injecting in warm water
maintained at 60°c through 14 gauge
needle at 0.25 ml/min
Ether is vaporized
Niosomes
22

23. 23

24. 3) preparation of multilamellar vesicles
a) Hand shaking method
Surfactant + cholesterol + volatile
organic solvent
Remove organic solvent at room
temperature by rotary evaporator
Thin layer formed on the wall of flask
Multilamellar niosomes
Film can be rehydrated with drug &
aqueous phase
24

25. 25

26. b) Trans membrane pH gradient drug uptake
process (remote loading)
Surfactant + cholesterol in chloroform
Hydrated with citric acid by vortex mixing
freezing & thawing then sonication
Addition of aqueous drug solution & vortexed
pH raised to 7.0-7.2 by 1M disodium phosphate
Multilamellar niosomes
Thin film is deposited on the wall of RBF
26

27. 4) MISCELLANEOUS METHOD :
a) Multiple membrane extrusion method
Surfactant + cholesterol + diacetyl
phosphate dissolved in chloroform
Niosomes
Pass the mixture through a series of
8 polycarbonate membrane
Aq. drug solution is added to above
mixture
Solvent evaporation to form thin film
27

28. 28

29. b) The “Bubble” Method29

30. c) 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
30

31. SEPARATION OF UNENTRAPPED
DRUGS
 The removal of unentrapped solute from the vesicles can be accomplished by
various techniques, which include:
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.
Dialysis:
 The aqueous niosomal dispersion is dialyzed in a dialysis tubing against
phosphate buffer or normal saline or glucose solution
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.
31

32. FACTORS AFFECTING THE PHYSICOCHEMICAL
PROPERTIES OF NIOSOMES
Membrane Additives:
 Stability of niosomes can be increased by the number of additives into
niosomal formulation along with surfactant and drugs.
 e.g. Addition of cholesterol in niosomal system increases the rigidity and
decreases the drugs permeability through the membrane
Temperature of Hydration:
 Shape and size of niosome is also influenced by the hydration temperature.
Assembly of the niosomes vesicles is affected by the temperature change of
niosomal system. Temperature change can also induce the vesicle shape
transformation
32

33. PROPERTIES OF DRUGS
 The drug entrapment in niosomes is affected by molecular weight, chemical structure,
hydrophilicity, lipophilicity of the drug. Vesicle size may increase due to entrapment of
drug.
Nature of the drug Leakage from the
vesicle
Stability
33

34. AMOUNT AND TYPE OF SURFACTANT
 As the HLB value of surfactants like span 85 (HLB 1.8) to span 20 (HLB 8.6)
increased, the mean size of niosomes also increases proportionally.
 Entrapment efficiency is also affected by phase transition temperature i.e. span 60
having higher TC, provide better entrapment efficiency.
 Entrapment efficiency of the niosomes is affected by the HLB value for e.g.
niosomes have high entrapment efficiency at HLB value 8.6 but HLB value 14 to
17 is not suitable for niosomes formulation
34

35. Structure of Surfactants
 The geometry of vesicles to be formed from surfactant is affected
by its structure, which is related to critical packing parameter (CPP)
where V= hydrophobic group volume
Ic = the critical hydrophobic group length
a0 = the area of hydrophilic head group
spherical micelles formed if CPP<0.5, inverted micelles is formed if
CPP>1. 37
35

36. Resistance to Osmotic Stress
 Diameter of niosomal vesicles was found to be decreased when niosomal
suspension is kept in contact with hypertonic salt solution. There is slow release
with slight swelling of vesicles, which is due to inhibition eluting fluids from
vesicles, followed by faster release, which may be due to decrease in mechanical
strength under osmotic stress
36

37. Characterization of niosomes
 Physical characterization
 Chemical characterization
 Biological characterization
37

38. Physical characterization38

39. 39

40. Chemical characterization40

41. Biological characterization
41

42. Therapeutic applications of Niosomes
1) For Controlled Release of Drugs
2) To Improve the Stability and Physical Properties of the Drugs
3) For Targeting and Retention of Drug in Blood Circulation
42

43. 1)To Prolong the Release Rate of Drugs
1.1 For Controlled Release
 The release rate of drugs like withaferin and gliclazide from the niosomes was found
slower as compared to other dosage forms
1.2 In Ophthalmic Drug Delivery
 Experimental results of the water soluble antibiotic gentamicin sulphate showed a
substantial change in the release rate. Beside this, the percent entrapment efficiency of
gentamicin sulphate was altered when administered as niosomes. Also, as compared to
normal drug solution, niosomes of drug show slow release
 Niosomal formulation containing timolol maleate (0.25%) prepared by chitosan coating
exhibited more effect on intra ocular tension with fewer side effects as compared to the
marketed formulation.
43

44. 2) To Improve the Stability and
Physical Properties of the Drugs
2.1 To Increase Oral Bioavailability :
 the formulation of niosomes, the oral bioavailability of the acyclovir as well as griseofulvin
was increased as compared to the drug alone.
2.2 For Improvement of Stability of Peptide Drugs :
 Niosomes prepared by the span 60 has high resistance against proteolytic enzyme and
exhibit good stability in storage temperature.
44

45. 2.3 To Promote Transdermal Delivery of Drugs
 Niosomes enhance the uptake of drugs through the skin.
 Cosmetics : topics use of niosome entrapped antibiotics to treat acne is done .
2.4 To Improve Anti-inflammatory Activity
 Niosomal formulation of diclofenac sodium prepared with 70% cholesterol showed greater
anti-inflammatory effect as compared to the free drug.
 Similarly, nimesulide and flurbiprofen showed greater activity than the free drug
45

46. 3.For Targeting and Retention of Drug
in Blood Circulation
3.1 For Increased Uptake by A431 Cells [a model cell line (epidermoid carcinoma)
used in biomedical research]
 Chitosan based vesicles incorporating transferrin and glucose as ligand have been
reported. These vesicles bind CoA (co-A) to their surface. Chitosan containing vesicles
are then taken up by A431 cells and the uptake was found to be enhanced by
transferrin.
3.2 For Liver Targeting
 Methotrexate was reported to be selectively taken up by liver cells after administration
as a Niosomes can also be used as a niosomal drug delivery system.
3.3 To Improve the Efficacy of Drugs in Cancer Therapy
 Most antineoplastic drugs cause severe side effects
 Niosomes can alter the metabolism , prolong half life of the drug and decreasing the
side effects of the drugs .
46

47. 3.4 In Treatment of Localized Psoriasis
 In the treatment of localized psoriasis, niosomes of methotrexate taking chitosan
as polymer have shown promising results
3.5 In Leishmaniasis
 The leishmaniasis parasite mainly infects liver and spleen cells.
 The commonly used drugs, antimonials, may damage the body organ like heart,
liver, kidney etc.
47

48. 3.6 Carrier for Haemoglobin
 Niosomes play an important role as a carrier for haemoglobin. The niosomal haemoglobin suspension was
found to give superimposable curve on free haemoglobin curve
Usefulness of Niosomes in Cosmetics
 Elastic niosomes showed increased permeation through the skin which will be beneficial for topical anti-
aging application.
 suitable for skin moisturising and tanning products
 Niosomes were prepared as possible approach to improve the low skin penetration and bioavailability
shown by conventional topical vehicle for minoxidil.
48

49. 49

50. Marketed products
 Lancome has come out with a variety of
anti-ageing products which are based on
niosome formulations. L’Oreal is also
conducting research on anti-ageing cosmetic
products.
50

51. 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, 6 th Edn.,
vallabh prakashan, 6, 306-307
4. International journal of pharmaceutical Science and Nanotechnology
volume 1,issue 1, April-June 2008
5. Shailendra Kumar Singh et.al, Niosomes: A Controlled and
Novel Drug Delivery System, Biol. Pharm. Bull. 34(7) 945—953(July, 2011)
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