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AITHA SWETHA
M.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
LIPOSOMES
1
Liposome =Phospholipid+
cholesterol
Hydrophillic head
Hydrophobic tail
Polar Lipids
(Phospholipid)
Lipid Soluble
ingredients
(Drugs,Nutrients
& vitamins)
H2O Layer Water Soluble
ingredients
(Drugs, Nutrients 5
& vitamins)
components of liposomes:
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.
10
Molecules of PC are not soluble in water.
In aqueous media they align themselves closely 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
PHASE TRANSITION
TEMPERATURE
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?
14
Mechanism of liposome formation:
15
Classification of liposome :
Classification
of liposome
16
Lamella :
SUV
MUV 20-100nm
GUV LUV
>1um >100nm 18
B. Based on REV, SUV made
method of by reverse
phase
preparation: evaporation
method
VET
SPLV
Vesicles Based on
method of Stable
prepared by
preparation plurilamenar
extrusion
vesicles
tech.
FATMLV
Frozen &
thawed MLV 19
Based on
composition
and convential
application:
immuno fusogenic
Based on
composition
& application
Long pH
circulatory sensitive
cationic
20
MethodS of Liposome Preparation
Passive
Loading of the entrapped agents
loading before/ during the manufacture
technique procedure.
21
Methods of liposome preparation
23
1. Mechanical dispersion method:
Lipid dissolve in organic solvent/co-solvent
Film deposition
Liposome
Post Hydration vortexing, sonication, freeze thawing &
high pressure extrusion 24
There are four basic methods of physical/mechanical
dispersion :
Hand shaken method.
Non shaking method.
Pro – liposomes .
Freeze drying .
25
Lipidsform stacks of film
from organic solution
(FE/HS)
Then film is treated with
aqueous medium
26
Pro-liposomes:
To increase the surface area of dried lipid film & to
facilitate instantaneous hydration.
lipid Dried
over
Finely divided
lipid particulate support Pro - liposomes
like powdered NACL/
sorbital
centrifugation 30 min
clear SUV 29
Dispersion.
Micro emulsification liposomes:
30
Micro fluidizer
French pressure cell liposomes:
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
32
Dried reconstituted vesicles& freeze thaw sonication method
33
pH induced vesiculation:
The transient change in pH brings about
an increase in surface charge of the lipid
bilayer which induces spontaneous LUVs
vesiculation .
Reduced the pH
to 7.5
Exposed to high pH * Addition of
~ (addition of 1M 0.1M Hcl
Preformed NaoH)
MLV’S
~Period of
(2.5-3.0)
exposure < 2min
MLVs 34
Cochleate method:
Cochleates
Removal
of Ca++ by
Cylindrical EDTA
rolls(cochleate
Addition of cylinders)
Ca++ ions
SUVs made
from
phosphatidylse
rine(PS)
35
Solvent dispersion methods:
Lipid dissolve in organic solvent
Liposome
Note:- Organic solvent miscible with aqueous phase
36
Solvent dispersion methods:
ETHANOL INJECTION/ETHER INJECTION:
37
De-Emulsification method:
Mechanical agitation
Microscopic water
droplets
Methods to prepare the droplets:
~Double emulsion vesicles
~Reverse phase evaporation vesicles 38
~Sonication methods
Reverse phase evapouration method:
39
DETERGENT SOLUBILISATIOIN METHODS
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 CHEMICA L CHARACTERISATION
5. Osmolarity Osmomete
46
Characterization parameters Analytical method/Instrument
STABILITY OF LIPOSOMES:
Stability invitro .
~ Lipid oxidation
~ Lipid peroxidation
~ Long term & accelerated stability
Stability after systemic administration.
47
1. Endocytosis 2. Adsorption
48
Encapsulation of drugs in liposomes:
• 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
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
50
DNA delivery of Genes by Liposomes
No immune response
Especially good
for in-lung delivery (cystic fibrosis)
52
Liposomes could serve as tumor specific vehicles
(even without special targeting)
54
NAME TRADE NAME COMPANY INDICATION
Liposomal Abelcet Enzon Fungal infections
amphotericin B
Liposomal Ambisome Gilead Sciences Fungal and protozoal infections
amphotericin B
Liposomal cytarabine Depocyt Pacira (formerly Malignant lymphomatous meningitis
SkyePharma)
Liposomal DaunoXome Gilead Sciences HIV-related Kaposi’s sarcoma
daunorubicin
Liposomal doxorubicin Myocet Zeneus Combination therapy with cyclophosphamide in
metastatic breast cancer
Liposomal IRIV vaccine Epaxal Berna Biotech Hepatitis A
60
Classification of niosomes
Small Large
Unilamellar Unilamellar Multilamellar
Vesicle Vesicle Vesicle
(SUV) (LUV) (MLV)
61
Components of niosomes:
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 of
Niosomes.
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
62
alkyl group chain
length : C12-C18
Shud be above Span surfactants
the gel to liquid with HLB values
phase transition 4 and 8
temperature of Hydration Non-ionic
the system Temperature surfactant
nature
Factors
affecting
Surfactants niosomes
and lipid Membrane
formation additives
levels
surfactant/lipid
ratio: 10-30 mM Nature of Cholesterol: Prevent
encapsulated vesicle aggregation.
drug Dicetyl phosphate: -ve
charge
63
Concept of Critical Packing Parameter
< 0.5 (indicating a large contribution from the hydrophilic head group
area) is said to give spherical micelles.
65
Methods of Niosome preparation:
Hand Shaking method
Bubble method
Sonication
From Proniosomes
66
Hand shaking method:
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.
sonication:
Surfactant +cholesterol Mixture is sonicated for 3
mixture is dispersed in 2 ml min at 60 C using titanium
aqueous phase in vial probe sonicator
Unilamellar niosomes 68
14 guage needle
Ether injection Method:
69
Multiple membrane extrusion Method:
•Mixture of surfactant, cholesterol and
dicetyl phosphate in chloroform is made
into thin film by evaporation
70
Bubble method:
RBF as bubbling unit with three necks in water
It is novel technique for the bath.
• 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:
Oral
immunological Diagnostic
Leishmaniasis Oncology drug Transdermal
adjuvants imaging
delivery
75
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
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 2,6-16
4. 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