niosomes introduction structure of niosomes advantages of niosomes types of niosomes formulation aspects different types of surfactants used different methods of preparation difference between liposomes and niosomes loading methods characterizations of niosomes modification aspects of niosomes

1. NIOSOMES
PRESENTED TO: PRESENTED BY:
DR. RAKESH PAHWA AKASH
M PHARMA 2ND SEM
INSTITUTE OF PHARMACEUTICAL
SCIENCES, KUK

2. INTRODUCTION
Niosomes are vesicles composed of hydrated non-ionic surfactants
in addition to cholesterol or its derivatives
Capable of encapsulating both hydrophilic & hydrophobic
substances
Hydrophilic encapsulate or adsorbed in vascular aqueous or bilayer
surface
Lamellar structure (Unilamellar or multilamellar)
 Bilayer non-ionic surface active agents
 Nanometric in size
 Osmotically active & stable

3.  Hydrophobic substances encapsulated by partioning into
lipophilic domain of bilayer
 Agitation hydrated lipid sheets detach & self associate to form
vesicles, preventing interaction of water with hydrocarbon core of
bilayer at edge
 Entrapping various types of drugs, genes, proteins & vaccines
 Biodegradable, biocompatible & non-immunogenic

4. STRUCTURE OF NIOSOMES

5. ADVANTAGES
 Osmotically active, chemically stable & long storage time
 Surface formation & modification very easy
 High compatibility with biological system & low toxicity
 Entrap lipophilic drugs into vesicular bilayer membranes &
hydrophilic drugs in aqueous compartments
 Improve therapeutic performance
 High patient compliance
 Access to raw material is convenient
 Increase oral bioavailability & skin penetration of drug
 Enhance absorption of some drugs across cell membrane

6. TYPES OF NIOSOMES
Divided into three categories:
 SMALL UNILAMELLAR VESICLES (10-100nm)
 LARGE UNILAMELLAR VESICLES (100-3000nm)
 MULTI-LAMELLAR VESICLES (>1 BILAYER)

8. FORMULATION ASPECTS
 NON-IONIC SURFACTANTS
 Amphiphilic molecules (hydrophilic & hydrophobic)
 E.G.- PHOSPHOLIPIDS
 Lipophilic chain made of alkanes, fluorocarbons, aromatic or other
non polar groups
 Head group involves highly solvated hydrophilic functionalities such
as sulfonates, carboxylates, phosphonates & ammonium derivatives
 Non-ionic surfactant has no charge group in its head
 If head charge is positive it called cationic surfactant
 If head has two oppositely charged group it termed amphoteric
(ZWITTERIONIC) surfactant
 Cationic surfactants are irritant & even toxic

9. Surfactant class Examples
Non-ionic
Polyoxyethylene alcohol,
Polyoxyethylene glycol alkyl ether (Brij),
Alkyl ethoxylate, Alkyl phenol ethoxylate
Anionic
Stearate, Soap, Alkyl benzene
sulphonate, Alkyl sulfate, Ether sulfates,
Alkyl ether sulphate
Cationic
Laurylamine, Trimethyl
dodecylammonium, Cetyl
trimethylammonium, Alkyl diamine salt,
Benzylalkyldimethylammonium salts,
Alkyl quaternary ammonium salts
Zwitterionic
Dodecyl betaine, Lauramidopropyl
betaine, Cocoamido-2-hydroxypropyl
sulfobetaine, Alkyl imidazoline,
Alkylbetaine, Sulfur-containing
amphoterics

10. MOST USED SURFACTANT
Span
• Span-85
• Span-65
• Span-80
• Span-60
• Span-40
• Span-20
Tween
• Tween-65
• Tween-85
• Tween-60
• Tween-80
• Tween-40
• Tween-20
Brij
• Brij-52
• Brij-30
• Brij-56
• Brij-58
• Brij-35

11. HYDROPHILIC-LIPOPHILIC
BALANCE (HLB)
• Plays role in controlling drug entrapment efficiency
• Dimensionless parameter for surfactant
• HLB Range 0 to 20 for non-ionic surfactants
• HLB <9 refers to lipophilic surfactant
• HLB >11 to hydrophilic surfactant
• HLB 3-8 are compatible with bilayer surface preparation (w/o
emulsifier)
• HLB 8-18 exhibit oil in water (o/w) emulsifier

12. CRITICAL PACKING PARAMETERS
(CPP)
• Play role in predicting vesicle forming ability, chemical structure &
various other factors
CPP = V/ LC A0
WHERE V – Hydrophobic group volume
LC – Critical hydrophobic group length
A0 – Area of hydrophilic head group
• CPP <1/3 have ability to form spherical micelles
• 1/3<CPP<1/2 for non-spherical micelles
• ½<CPP<1 for bilayer vesicles
• CPP≥1 for inverted micelles

13. GEL LIQUID TRANSITION
TEMPERATURE (TC)
• Have direct effect on entrapment efficiency
• Span-60 with high TC exhibits highest entrapment efficiency
ADDITIVE AGENT
 Cholesterol content: for surfactants with HLB >6, cholesterol added
in order to form a bilayer vesicles
 Lower HLB values, cholesterol enhances stability of vesicles by
promoting TC of vesicles
 Dicetyl phosphate (DCP) additive charge inducer used to impart
negative charge on surface of niosomes to stabilize bilayer
 Increasing amt of DCP beyond limit prevent formation of niosomes

15. Ether Injection Method

16. Thin Film Hydration Technique

17. Hand Shaking Method

18. BUBBLE METHOD

19. SONICATION METHOD

20. FREEZE & THAW METHOD (FAT)

21. Loading
methods
Direct
entrapment
(Passive
loading)
Remote loading
(Active loading)
Remote loading by
using trans membrane
pH GRADIENT
(INSIDE ACIDIC)
Remote loading by
using trans membrane
ion gradient

22. Reverse Phase Evaporation
Method

23. Heating Method

24. Proniosomes

25. Difference Between Liposomes &
Niosomes

26. CHARACTERIZATION
 VESICLE SIZE & MORPHOLOGY
 VESICLE CHARGE
 BILAYER RIGIDITY & HOMOGENEITY
 NIOSOMAL DRUG LOADING & ENCAPSULATION
EFFICIENCY
 NIOSOMAL DRUG RELEASE

27. Vesicle Size & Morphology
 20 nm TO 50 nm
 Light microscopy & Coulter counter (upto 1µm)
 Electron microscopic analysis & Light scattering technique
(submicron range)
 Scanning electron microscopy
 Atomic force microscopy
 Cryo transmission electron microscopy
 Transmission electron microscopy & Freeze fracture
technique are also used for analysis of no. of bilayers.

28. VESICLE CHARGE
 More Stable Against Aggregation & Fusion
 DYNAMIC LIGHT SCATTERING Measure Zeta
Potential
 Microelectrophoresis measure surface potential
 pH sensitive fluorophores

29. BILAYER RIGIDITY &
HOMOGENEITY
 Rigidity Influences Biodistribution & Biodegradation
 Homogeneity identified by:
 P-NMR
 Differential Scanning Calorimetry (DSC)
 Fourier Transform-infra Red Spectroscopy (FT-IR)
 Fluorescence resonance energy transfer (FRET) used for
deeper insight about shape, size & structure

30. Niosomal Drug Loading &
Encapsulation Efficiency
Sediment Washed With Distilled Water To Remove Absorbed Drug
Supernatant Removed
Ultra centrifuged
Niosomal Suspension

31. excipientdrugpolymerofamt
100recoveredniosomesof
)recovery(%Niosomes 

 amt
recoveredniosomesofamt
100niosomesindrugof
(%)loadingDrug 
 amt
useddrugofamt
100niosomesindrugofamt
(%)efficiencyEntrapment 


32. Niosomal Drug Release
 FRET used for Drug Release Monitoring
 In-Vitro release method
 Dialysis bags or dialysis membrane used to minimize
interference

33. MODIFICATION
• Enhance wettability and decrease side effects
• Amount of modifying agents determined by
• NMR
• FTIR
• PEG (polyethylene glycol): highly hydrophilic
• Prevent uptake through reticulo-endothelial-
system(RES)
• Prolonged circulation & target search time

34. RECENT RESEARCHES
Loaded drug Highest entrap
efficiency
(EE%)
Type of
surfactant
Preparation
method
Antioxidants
(Gallic acid,
Ascorbic acid)
59.40 ± 1.43 Tween – 60 TFH
Methotrexate 94.8 ± 4.6 TFH
Diclofenac
sodium
(DCS)
48.37 ± 2.07
58.20 ± 1.75
50.14 ± 2.11
Span –
20,40,60,80,85
Tween –
20,40,60,80
HSM
EIM
REV
Curcumin 74.5 ± 3.2 Tween – 20,80 Sonication
method
Ellagic acid 38.73 ± 1.58
Span – 60
Tween - 60 REV