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LIPOSOMES & NIOSOMES
DEPARTMENT OF PHARMACEUTICS
S.R.R COLLEGE OF PHARMACEUTICAL SCIENCES
ELAKATHURTHY(M),VALBHAPUR(V),KARIMNAGAR
Presented by;
AITHA SWETHAM.PHARMACY 1ST YEAR 2ND SEM
• Introduction• Structure of liposomes • Advantages& disadvantages• Components of liposome• Mechanism of liposome• Preparation methods of liposomes• Characterization of liposomes• Applications of liposomes • Summary• Niosomes Introduction • Advantages& disadvantages• Preparation methods of niosomes• Characterisation of niosomes• summary
• References
CONTENTS:
LIPOSOMES
liposomes are concentric bilayered
vesicles in which an aqueous volume is
entirely enclosed by a membraneous
lipid bilayer mainly composed of natural
or synthetic phospholipids.Liposomes were first produced in England in 1961 by
Alec D. Bangham. The size of a liposome ranges from some
20 nm up to several micrometers
1
Structure Of Liposome
Hydrophillic headHydrophobic tail
The lipid moecules are usually
phospholipids-amphipathic
moieties with a hydrophilic head group
and two hydrophobic tails.
Liposome =Phospholipid+ cholesterol
2
Provides selective passive targeting t
o tumor tissues.
(liposomal doxorubicin) .
Increased efficacy and therapeutic in
dex.
Reduction in toxicity of the encapsula
ted agent.
Site avoidance effect (avoids non-
target tissues).
Improved pharmacokinetic effects .
Flexibility to couple with site-
specific ligands to achieve
active targeting.
Advantages of liposomes:
3
Disadvantages of liposomes:
Production cost is high.
Leakage and fusion of
encapsulated drug /
molecules.
Sometimes phospholipid
undergoes oxidation and
hydrolysis like reaction.
Short half-life.
Low solubility.
4
H2O Layer
Polar Lipids
(Phospholipid)
Water Soluble ingredients(Drugs, Nutrients
& vitamins)
Lipid Soluble ingredients(Drugs,Nutrients & vitamins)
Cross-section of liposomes:
5
components of liposomes:
The structural components of
liposomes include:
A. Phospholipids
B. cholesterol
6
A. General representation of phospholipids:
7
Phospholipids
Phosphatidylcholine- natural
Amphipathic molecule Hydrophilic polar head-
Phosphoric acid bound to water soluble molecule.
Glyceryl bridge Hydrophobic tail-
2 fatty acid chain containing 10-24 carbon atoms and 0-6 double bond in each chain.
The amphipathic molecule self organise in ordered supramolecular structure when confronted (meet face to face) with solvent.
8
The most common natural phospholipid
is the phospatidylcholine (PC ).
Naturally occurring phospholipids
used are :
PC: Phosphatidylcholine.
PE: Phosphatidylethanolamine.
PS: Phosphatidylserine
Synthetic phospholipids used are:
DOPC: Dioleoyl phosphatidylcholine
DSPC: Disteroyl
phosphatidylcholine
DOPE: Dioleoyl
phosphatidylethanolamine
DSPE: Distearoyl
phosphatidylethanolamine
Polar Head Groups
Three carbon glycerol
9
Molecular geometry on structure of amphiphillic aggregates:
10
Molecules of PC are not soluble in water.
In aqueous media they align themselves close
ly in planar bilayer sheets
in order to minimize the
unfavorable action between the bulk aqueous
phase and the long hydrocarbon fatty chain.
Such unfavorable interactions are completely
eliminated when the
sheets fold on themselves to form closed
sealed vesicles
11
At various temperatures, phospholipid membranes can exist in different phases. The transition from one phase to another can be detected by technique like micro calorimetry . What exactly happens during phase transition?
Tightly ordered At elevated temperature liquid crystal phase gel state ( lipid membrane) (movement is higher) This is due to the fatty acid chain adopting a new conformation other than all trans straight chain configuration, such as gauche configuration state( phenomenon- chain tilt )
PHASE TRANSITION TEMPERATURE
12
B. Cholesterol:
Cholesterol stabilizes the Membrane
Steroid lipid
Interdigitates between phospholipids.
i.e. below Tc , it makes membrane less
ordered & above Tc more ordered.
Being an amphipathic molecule, cholesterol inserts into the membrane with its hydroxyl group of cholesterol oriented towards the aqueous surface and aliphatic chain aligned parallel to the acyl chains in the center of the bilayer .
13
Role of cholesterol in bilayer formation:
Cholesterol act as fluidity bufferAfter intercalation with
phospholipid molecules alter the freedom of motion of carbon
molecules in the acyl ChainRestricts the transformations of
trans to gauche Conformations.Incorporated into phospholipid
membrane upto 1:1 or 2:1 of cholesterol to PC.
14
Mechanism of liposome formation:
15
Classification of liposome :
Classification of liposome
Structural parameters
Method of preparation
Composition and application
16
Types of vesicles based on lamella
Lamella :
17
Based on structural parameters
MLVMultilam
ellar Large
vesicles(>0.5 um)
OLV oligolamellar
vesicles(>0.1-1.0
um)
UV Unilam
ellarVesicle
s
MVVMultivesicularvesicles
(> 1.0 UM)
MUV
GUV>1um
SUV20-
100nmLUV>100n
m
A. Structural parameters:
18
Based on
method of
preparation
REV, SUV made by reverse phase
evaporation
method
SPLVStable plurilamenar vesicle
s
FATMLVFrozen
& thawed
MLV
VETVesicle
s prepare
d by extrusi
on tech.
B. Based on method of preparation:
19
Based on
composition &
application
conventia
l
fusogenic
pH sensitive
cationic
Long circulatory
immuno
Based on composition and application:
20
Passive loading
technique
Active/remote loading
technique
Loading of the entrapped agents before/ during the manufacture procedure.
Certain types of compounds with ionizable groups & those with both lipid & water solubility can be Introduced into liposomes after the formation of intact vesicles.
MethodS of Liposome Preparation
21
LIPID FILM HYDRATION BY HAND SHAKING,FREEZE DRYING OR NON HAND SHAKING
MICRO EMULSIFICATION
SONICATION
FRENCH PRESSURE CELL
MEMBRANE EXTRUSON
DRIED RECONSTITUTED VESICLES
ETHANOL INJECTION
ETHER INJECTION
DOUBLE EMULSION
REVERSE PHASE
VAPOURATION VESICLES
STABLE PLURI LAMELLER
VESICLES
DETERGENT REMOVAL
FORM MIXED MICELLES
BY DIALYSIS
CHROMATIGRALPY
DIFFUSION
VESICLES LIKE….
RECONSTITUTED &
SANDAI VIRUS ENVELOPE
Methods of liposome preparation
Passive loading techniques
Active loading techniques
Mechanical dispersion methods
Solvent dispersion methods
Detergent removal technique
22
General Method Of Liposome Preparation:
23
1. Mechanical dispersion method:
24
There are four basic methods of
physical/mechanical dispersion :
Hand shaken method.
Non shaking method.
Pro – liposomes .
Freeze drying .
25
Lipid film hydration by hand shaking method:
Lipids form stacks of film from organic solution (FE/HS)Then film is treated with aqueous medium
Upon hydration lipids swell and peel out from RB flask
vesiculate to form Multi lamellar vesicles(MLVs)
26
Pro-liposomes:
To increase the surface area of dried lipid film & to facilitate instantaneous hydration.lipid Dried
over
lipid
Finely divided
particulate support like powdered
NACL/ sorbital
Pro - liposomes
Pro- liposomes
water
Dispersion of MLV’S
This Method overcome the stability problem.
27
Micro Emulsification liposomes (MEL)
Sonicated unilamellar vesicles (SUVs)
French Pressure Cell Liposomes .
Membrane extrusion Liposomes
Dried reconstituted vesicles(DRVs)
Freeze thaw sonification (FTS)
pH induced vesiculation
Cochleate method.
Processing of the lipids hydrated by
physical means or the mechanical
treatments of MLVs :
28
Sonicated unilamellar vesicles:
The exposure of MLVs to ultrasonic irradation for producing small vesicles.
Probe sonicator Bath sonicatorUsed for dispersions large volume require high of dilute lipidsenergy insmall volumes
SonicationMLVs hazy transparent 5-10 min solution centrifugation 30 min
clear SUV Dispersion.
29
Micro emulsification liposomes:
Micro fluidizer 30
French pressure cell liposomes:
Extrusion of preformed large liposomes in french press under very high pressure .
uni or oligo lamellar liposomes of intermediate size (30-80nm ) .
Advantages Less leakage and more stable liposomes are formed compared to sonicated forms
31
Vesicles prepared by extrusion technique :
The size of liposomes is reduced by gently passing them through polycarbonate membrane filter of defined pore size at lower pressure
Used for preparation of LUVs and MLVs
32
Dried reconstituted vesicles& freeze thaw sonication method
33
pH induced vesiculation:
Preformed MLV’S(2.5-3.0)
Exposed to high pH~ (addition of 1M NaoH)~Period of exposure < 2min
Reduced the pH to 7.5* Addition of 0.1M Hcl
The transient change in pH brings about an increase in surface charge of the lipid bilayer which induces spontaneous vesiculation .
MLVs
LUVs
34
SUVs made from phosphatidylserine(PS)
Addition of Ca++ ions
Cylindrical rolls(cochleate cylinders)
Removal of Ca++ by EDTA
Cochleate method:
Cochleates
35
Note:- Organic solvent miscible with aqueous phase
Solvent dispersion methods:
36
Solvent dispersion methods:ETHANOL INJECTION/ETHER INJECTION:
37
De-Emulsification method:
Generally the liposome is made up
in 2 steps:
1 st the inner leaflet of the bilayer .
Then the outer half.
Methods to prepare the droplets: ~Double emulsion vesicles ~Reverse phase evaporation vesicles ~Sonication methods
Aqueous medium containing material to be entrapped
Add to immiscible organic solution of lipid
Mechanical agitation
Microscopic water droplets
38
Reverse phase evapouration method:
39
Note:- Liposome size and shape depend on chemical nature of detergent, concentration and other lipid involved
Below CMC, detergent molecules exist in free soln. As the concentration is increased, micelles are formed.
DETERGENT SOLUBILISATIOIN METHODS
Methods to remove detergents: Dialysis Column chromatography.
40
Active/remote loading technique:The lipid bilayer membrane is impermeable to
ions & hydrophilic molecules. But,
Permeation of hydrophobic molecules can be
controlled by concentration gradients.
Some weak acids or bases can be transported
due to various transmembrane gradients
Electrical gradients.
Ionic(pH) gradients.
Chemical potential gradients.
Weak amphipathic bases accumulate in
aq phase of lipid vesicles
in response to difference in pH b/w
Inside & outside of
liposomes
41
pH gradient is created by preparing liposomes with low internal pH.
Addtn of base to extraliposomal medium.
[Basic compds ( lipophilic (non ionic) at high pH & hydrophilic(ionic) at low pH)]
Lipophilic (UNPROTONATED) drug diffuse through the bilayer
At low pH side, the molecules are predominantly protonated .
Exchange of external medium by gel extrusion chromatorapghy with neutral solution.
Weak bases like doxorubicine, adriamycin and vincristine are encapsulated.
Solute bearing no charge at neutral pH
Liposomes with low internal pH
Neutral solute passes easily through bilayer membrane by diffusion
Charge aquired by solute inside liposomes makes them unable to exit 42
Locus of drugs in liposomes:Hydrophilic (DOXORUBICIN) Low entrapment Leakage Hydrolytic degradation Lipophilic (CYCLOSPORINE)High entrapment Low leakage Chemical stability
Ampiphilic (VINBLASTIN) High entrapment Rapid leakage Biphasic insoluble (ALLOPURINOL, 6-MERCAPTOPURINE) Poor loading & entrapment
43
Characterization of liposomes:
PHYSICAL CHARACTERISATION
→ Vesicles size/shape/morphology
→ Surface -charge/electrical potential
→ Phase behaviour/ lamellarity
→ Drug release
→ % capture /free drug
CHEMICA L CHARACTERISATION
→ Phospholipids /lipid concentration
→ Drug concentration
→ PH / Osmomolality
→Antioxidant degradation
→ Phospholipids / cholesterols –
peroxidation/oxidation/hydrolysis
BIOLOGICAL CHARACTERISATION
→ Sterility
→ Pyrogenisity
→ Animal toxicity
→Plasma Stability: 44
Characterization parameters
Analytical method/Instrument
1. Vesicle shape and surface morphology
Transmission electron microscopy, Freeze-fracture electron microscopy
2.Mean vesicle size and size distribution (submicron and micron range)
Photon correlation spectroscopy, laser light scattering, gel permeation and gel exclusion
3. Surface charge Free-flow electrophoresis
4. Electrical surface potential and surface pH
Zetapotential measurements
5. Lamellarity Small angle X-ray scattering, 31 P-NMR, Freeze-fracture electron microscopy
6. Phase behavior Freeze-fracture
electron microscopy, Differential scanning calorimetery
7. Percent of free drug/ percent capture
Minicolumn centrifugation, ion-exchange chromatography, radio labelling
8. Drug release Diffusion cell/ dialysis
1.PHYSICAL CHARACTERIZATION:
45
Characterization parameters
Analytical method/Instrument
1. Phospholipid concentration
Barlett assay, stewart assay, HPLC
2. Cholesterol concentration
Cholesterol oxidase assay and HPLC
3. Phopholipid peroxidation
UV absorbance
4. Phospholipid hydrolysis,
Cholesterol auto-oxidation.
HPLC and TLC
5. Osmolarity Osmomete
2. CHEMICAL CHARACTERIZATION:
46
Characterization parameters Analytical method/Instrument
1. Sterility Aerobic or anaerobic cultures
2. Pyrogenicity Limulus Amebocyte Lysate (LAL) test
3. Animal toxicity Monitoring survival rates, histology and pathology
3. BIOLOGICAL CHARACTERIZATION:
STABILITY OF LIPOSOMES: Stability invitro . ~ Lipid oxidation ~ Lipid peroxidation ~ Long term & accelerated stability Stability after systemic administration.
47
MODES OF LIPOSOMES/CELL INTERACTION:
1. Endocytosis
2. Adsorption
3. fusion 4. Lipid transfer
48
• Encapsulation volume/Trapped volume Volume of aqueous solution entrapped in liposomes per mole
of PL (µL/µmol PL)• Encapsulation Efficiency Assessed by mini column centrifugation method & protamine
aggregation method. protamine aggregation method used for neutral and
negetively charged liposomes. Liposome dispersion can be precipitated with protamine solution and subsequent centrifugation at 2000RPM.
By analysing the material in super natent & in liposome pellet ( after disrupting liposomal pellet with 0.6 ml of 10% triton x-100 ). The encapsulation efficiency of entrapped material can be estimated.
• % Encapsulation
Drug entrapped in liposomes x 100 Total drug added
Encapsulation of drugs in liposomes:
49
In gene delivery.
As drug delivery carriers.
Enzyme replacement therapy.
Chelation therapy for treatment of heavy
metal poisoning.
Liposomes in antiviral/anti microbial
therapy.
In multi drug resistance.
In tumour therapy.
In immunology.
In cosmetology
USES OF LIPOSOMES :
50
DNA delivery of Genes by Liposomes
Cheaper than viruses
No immune response
Especially good for in-lung delivery (cystic fibrosis)
100-1000 times more plasmid DNA needed for the same transfer efficiency as for viral vector
51
Lipofection
52
Liposomes could serve as tumor specific vehicles (even without special targeting)
Liposomes better penetrate into tissues with disrupted endothelial lining 53
DRUG ROUTE OF ADMINISTRATION
APPLICATION TARGETED DISEASES
Amphotericin B Oral delivery Ergosterol membrane Mycotic infection
Insulin Oral,ocular,pulmonaryAnd transdermal
Decrease glucose level Diabetic mellitus
Ketoprofen Ocular delivary Cyclooxygenase enzyme inhibitor Pain muscle condition
Pentoxyfyllin Pulmonary delivery phosphodiesterase Asthama
Tobramycin Pulmonary delivery Protein synthesis inhibitor Pseudomonas infection,aeroginosa
Salbutamol Pulmonary delivery ß2-adrenoceptor antagonist Asthama
Cytarabin Pulmonary delivery DNA-polymerase inhibition Acute leukameias
Benzocaine Transdermal Inhibition of nerve impulse from sensory nerves
Ulcer on mucous surface with pain
Ketaconazole Transdermal Inhibit ergosterol membrane Candida albicans
Levanogesterol Transdermal Rhamnose receptor skin disorder
hydroxyzine Transdermal H1-receptor antagonist Urtecaria,allergic skin disease
Ibuprofen Oral delivery Chaemoceptor,free ending Rheumatoid arthritis
triamcilonone Ocular delivery,Transdermal Inhibition of prostaglandin Anti-inflammatory
Therapeutic application of liposomes:
54
NAME TRADE NAME COMPANY INDICATION
Liposomal amphotericin B
Abelcet Enzon Fungal infections
Liposomal amphotericin B
Ambisome Gilead Sciences Fungal and protozoal infections
Liposomal cytarabine Depocyt Pacira (formerlySkyePharma)
Malignant lymphomatous meningitis
Liposomal daunorubicin
DaunoXome Gilead Sciences HIV-related Kaposi’s sarcoma
Liposomal doxorubicin Myocet Zeneus Combination therapy with cyclophosphamide in metastatic breast cancer
Liposomal IRIV vaccine Epaxal Berna Biotech Hepatitis A
Liposomal IRIV vaccine Inflexal V Berna Biotech Influenza
Liposomal morphine DepoDur SkyePharma, Endo Postsurgical analgesia
Liposomal verteporfin Visudyne QLT, Novartis Age-related macular degeneration, pathologic myopia, ocularhistoplasmosis
Liposome-PEGdoxorubicin
Doxil/Caelyx Ortho Biotech,Schering-Plough
HIV-related Kaposi’s sarcoma, metastatic breast cancer, metastaticovarian cancer
Micellular estradiol Estrasorb Novavax Menopausal therapy
List of marketed products :
55
summary:
o liposomes are concentric bilayered vesicles
in which an aqueous
volume is entirely enclosed
by a membraneous lipid bilayer
o Liposomes are one of the unique drug
delivery system, in controlling
and targeting drug delivery.
o Components of liposomes include
phospholipid and cholesterol.
o Method of preparation of liposomes include
active loading technique
and passive loading technique.
o Passive loading techniques include solvent
mechanical dispersion,
solvent dispersion & detergent
solubilisation
o Characterization of liposomes include
physical,chemical and
biological.
56
NIOSOMES
INTRODUCTIONNiosomes are non-ionic surfactant based
unilamellar or multilamellar bilayer vesicles
up on hydration of non ionic surfactants
with or without incorporation cholesterol .
The niosomes are very small, and
microscopic in size. Their size lies in the
nanometric scale.
Niosomes are a novel drug delivery system,
in which the medication is encapsulated in a
vesicle. Both hydrophilic
& lipophilic drugs ,entrap either in the
aqueous layer or in vesicular membrane
made of lipid materials.
57
Structure of niosomes:
Head part (hydrophillic)Tail part (hydrophobic)Drug
molecules
Phospholipids
Polar heads facing hydrophilic region
Hydrophobic drugs localized in the hydrophobic lamellae
Hydrophilic drugs located in aqueous regions encapsulated
These vesicular systems are similar to liposomes that can be used as carriers of amphiphilic and lipophilic drugs.
It is less toxic and improves the therapeutic index of drug by restricting its action to target cells.
58
They are osmotically active and stable.
They increase the stability of the entrapped
drug.
The vesicle suspension being water based
offers greater patient compliance over oil
based systems
Since the structure of the niosome offers
place to accommodate hydrophilic, lipophilic
as well as ampiphilic drug moieties, they can
be used for a variety of drugs.
The vesicles can act as a depot to release the
drug slowly and of controlled release.
Biodegradable, non-immunogenic and
biocompatible.
Advantages of niosomes:
59
DISADVANTAGES OF NIOSOMES:
Aggregation
Fusion
Leaking of entrapped drug
Hydrolysis of encapsulated drugs
which limiting the shelf
life of the dispersion.
60
SmallUnilamellarVesicle(SUV)
LargeUnilamellarVesicle(LUV)
MultilamellarVesicle(MLV)
Typical Size Ranges: SLV: 20-50 nm – MLV:100-1000 nm
Classification of niosomes
61
Cholesterol and Non ionic surfactants are the two major components used for the preparation of niosomes.Cholesterol provides rigidity and proper shape. The surfactants play a major role in the formation of niosomes.non-ionic surfactants like spans(span 20,40,60,85,80), tweens (tween 20,40,60,80) are generally used for the preparation ofNiosomes. Few other surfactants that are reported to form niosomes are as follows : Ether linked surfactant Di-alkyl chain surfactant Ester linked Sorbitan Esters Poly-sorbates
Components of niosomes:
62
Factors Affecting Niosomes Formation
Factors affecting niosomes formation
Non-ionic surfactant
nature
Membrane additives
Nature of encapsulated
drug
Surfactants and lipid
levels
Hydration Temperature
alkyl group chain length : C12-C18
Span surfactants with HLB values 4 and 8
Cholesterol: Prevent vesicle aggregation.Dicetyl phosphate: -ve charge
surfactant/lipid ratio: 10-30 mM
Shud be above the gel to liquid phase transition temperature of the system
63
Prediction of vesicle forming ability is not a simply a matter of HLB
CPP = v/lca0
where v - hydrophobic group volume, lc - critical hydrophobic group length and a0 - area of the hydrophilic head group
CPP between 0.5 and 1 likely to form vesicles.
< 0.5 (indicating a large contribution from the hydrophilic head group area) is said to give spherical micelles.
>1 (indicating a large contribution from the hydrophobic group volume) should produce inverted micelles.
Concept of Critical Packing Parameter
64
Sl. No.
Liposomes Niosomes
1. Vesicles made up of concentric bilayer of phospholipids
Vesicles made up of surfactants with or without incorporation of cholesterol.
2. Size ranges from 10-3000nm Size ranges from 10-100nm
3. Comparatively expensive Inexpensive
4. Special storage condition are required
No such special requirement
5. Phospholipids used are unstable Non-ionic surfactants are stable
6. Comparatively more toxic Less toxic
Comparisition between liposomes & niosomes:
65
Hand Shaking method
Reverse phase evaporation technique
Ether Injection method
Multiple membrane
extrusion method
Bubble method
Sonication
From Proniosomes
Methods of Niosome preparation:
66
Hand shaking method:
Surfactant & cholesterol
(150µmole) solution is
dissloved in 10ml ether in
round bottom flask
Rotary evaporator
Ether is evaporated under
vacuum at room
temperature
hydration
Surfactant swells and
peeled off into a film like
lipids
swollen amphiphiles fold to
form vesicles.
Rotary evaporator
67
Reverse phase evaporation technique : Surfactant is dissolved in chloroform ond 0.25
volume of PBS buffer is emulsified to get a W/O emulsion. sonicated chloroform is evaporated under reduced pressure.
The lipid or surfactant forms a gel first and hydrates to form vesicles.
Free drug (unentrapped) is generally removed by dialysis.
sonication:Surfactant +cholesterol mixture is
dispersed in 2 ml aqueous phase in
vial
Mixture is sonicated for 3
min at 60°C using titanium probe
sonicatorUnilamellar niosomes 68
Ether injection Method:Surfactant : cholesterol (150µmole) solution is dissloved in ether
Slowly injected into preheated 4.0ml aqueous phase maintained at 60 c through a 14 gauge needle
Vaporization of ether leads to formation of single layered vesicles.
formation of a bilayer sheet, which eventually folds on itself to form sealed unilamellar vesicles.
14 guage needle
69
Multiple membrane extrusion Method: •Mixture of surfactant,
cholesterol and dicetyl phosphate in chloroform is made into thin film by evaporation
•The film is hydrated with aqueous drug solution and the resultant suspension extruded through polycarbonate membranes
70
Bubble method: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 70°C
Above dispersion is homogenized for 15 sec and then bubbled with nitrogen gas at 70°C to get niosomes
It is novel
technique for the
one step
preparation of
liposomes and
niosomes without
the use of
organic solvents. 71
proniosomes:
• Bubble Method• Formation of niosomes from
proniosomes:It is prepared by coating 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”.
72
Separation of
unentrapped drug
Dialysis
CentrifugationGel filtration
Separation of unentrapped drug:
Dialyzed in a dialysis tubing against phosphate buffer or normal saline
The unentrapped drug is removed by gel filtration of niosomal dispersion through a Sephadex-G-50 column and elution with phosphate buffered saline
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.
CentrifuserGel Filtration 73
Characterization of Niosomesa) Size, Shape and MorphologyFreeze Fracture Electron Microscopy:- Visualize the vesicular structure of surfactant based vesicles. Photon Correlation spectroscopy :- Determine mean diameter of the vesicles.Electron Microscopy :- Morphological studies of vesicles.b) Entrapment efficiency After preparing niosomal dispersion, unentrapped drug is separated by dialysis and the drug remained entrapped in niosomes is determined by complete vesicle disruption using 50% n-propanol or 0.1% Triton X-100 and analysing the resultant solution by appropriate assay method for the drug. c) Vesicle Suface ChargeDetermined by measurement of electrophoretic mobility and expressed in expressed in terms of zeta potential d) In vitro studies
74
Applications of Niosomes
Applications
Leishmaniasis
Oncology
immunological
adjuvants
Oral drug delivery
Transderm
al
Diagnosti
c imagi
ng
75
MARKETED PRODUCT:Lancôme has come out with a variety of anti-ageing products which are based on noisome formulations. L’Oreal is also conducting research on anti-ageing cosmetic products.
76
Summary :
Niosomes provide incorporating the drug into 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. Various type of drug deliveries can be possible using niosomes like targeting, ophthalmic, topical, parenteral etc.
77
REFERENCES:1. S.P. Vyas And R.K. Khar,targeted &
Controlled Drug Delivery,liposomes,173-279.
2. Mohammad Riaz, Liposomes :Preparation Methods, Pakistan Journal Of Pharmaceutical Sciences, January 1996,Vol.19(1),65-77.3. Sharma Vijay K1*, Liposomes: Present Prospective and Future Challenges,International Journal Of Current Pharmaceutical Review And Research, oct 2010,vol1, issue 2,6-164. Himanshu Anwekar*, Liposome- as drug carriers, International Journal Of Pharmacy & Life Sciences, Vol.2, Issue 7: July: 2011, 945-951
78
5. Madhav Nvs* And Saini A, Niosomes: A Novel Drug Delivery System, International Journal Of Research In Pharmacy And Chemistry, 2011, 1(3),498-511.6. Lohumi Ashutosh, Rawat Suman, A Novel Drug Delivery System: Niosomes Review, Journal Of Drug Delivery & Therapeutics; 2012, 2(5), 129-135.7. Pawar Sd *, Pawar Rg, Niosome: An Unique Drug Delivery System, International journal Of Pharmacy, Biology and Allied Sciences, April, 2012, 1(3): 406-416.8. Rajesh Z. Mujoriya, Niosomal Drug Delivery System – A Review, International Journal Of Applied Pharmaceutics, Vol 3, Issue 3, 2011,7-10.
79
Success in life mostly depends on the power of ‘CONCENTRATION’ --- Swami Vivekananda