Liposomes are spherical vesicles made of phospholipid bilayers that can encapsulate hydrophilic or hydrophobic drugs. They range in size from 25nm to 5000nm. This document discusses the structure of liposomes and their components, including phospholipids and cholesterol. It also covers various preparation methods such as lipid film hydration, extrusion, and detergent removal. Liposomes offer advantages for drug delivery such as the ability to encapsulate different drug types and provide controlled release, but also have challenges like high production costs and drug leakage.
Liposomes, Structure of liposome, phospholipids, classification of liposomes, method of preparation of liposomes, mechanism of liposome formation, application of liposomes.
Liposomes, Structure of liposome, phospholipids, classification of liposomes, method of preparation of liposomes, mechanism of liposome formation, application of liposomes.
Liposomes are concentric bilayered vesicles in which an aqueous core is entirely enclosed by a membranous lipid bilayer mainly composed of natural or synthetic phospholipids.
Liposomes are spherical microscopic vesicles consisting phospholipids bilayers which enclose aqueous compartments.
The size of a liposome ranges from some 20 nm up to several micrometers.
Liposomes were first produced in England in 1961 by Alec D. Bangham, who was studying phospholipids and blood clotting.
Small unilamellar vesicles (SUV), 25 to 100 nm in size that consist of a single bilayer
Large unilamellar vesicle (LUV), 100 to 500 nm in size that consist of a single bilayer
Multilamellar vesicle (MLV), 200 nm to several microns, that consist of two or more concentric bilayer
Liposomes-Classification, methods of preparation and application Vijay Hemmadi
liposome preparation and application
A liposome is a tiny bubble (vesicle), made out of the same material as a cell membrane. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases. Membranes are usually made of phospholipids, which are molecules that have a head group and a tail group
Introduction
Advantages & Disadvantages
Classification
Manufacturing of liposomes
Liposome characterization and control
Stability consideration for liposomal formulations
Regulatory science of liposome drug products
Drug release from liposomes
Applications
Recent innovations
Approved liposome products
Introduction
Structure
Niosomes Vs. Liposome
Advantages & Disadvantages
Properties of Niosomes
Method of Manufacturing
Evaluation of Niosomes
Applications
Marketed products
Liposomes are concentric bilayered vesicles in which an aqueous core is entirely enclosed by a membranous lipid bilayer mainly composed of natural or synthetic phospholipids.
Liposomes are spherical microscopic vesicles consisting phospholipids bilayers which enclose aqueous compartments.
The size of a liposome ranges from some 20 nm up to several micrometers.
Liposomes were first produced in England in 1961 by Alec D. Bangham, who was studying phospholipids and blood clotting.
Small unilamellar vesicles (SUV), 25 to 100 nm in size that consist of a single bilayer
Large unilamellar vesicle (LUV), 100 to 500 nm in size that consist of a single bilayer
Multilamellar vesicle (MLV), 200 nm to several microns, that consist of two or more concentric bilayer
Liposomes-Classification, methods of preparation and application Vijay Hemmadi
liposome preparation and application
A liposome is a tiny bubble (vesicle), made out of the same material as a cell membrane. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases. Membranes are usually made of phospholipids, which are molecules that have a head group and a tail group
Introduction
Advantages & Disadvantages
Classification
Manufacturing of liposomes
Liposome characterization and control
Stability consideration for liposomal formulations
Regulatory science of liposome drug products
Drug release from liposomes
Applications
Recent innovations
Approved liposome products
Introduction
Structure
Niosomes Vs. Liposome
Advantages & Disadvantages
Properties of Niosomes
Method of Manufacturing
Evaluation of Niosomes
Applications
Marketed products
liposomes are novel drug delivery dosage systems, where the drug is entrapped in phospholipid bilayered vesicles. the release of drug from the vesicles can be controlled or sustained.
the follwing presentation contain structure, classification and preparation methods, characterization and applications of liposomes.
Liposomes by Mr. Vishal Shelke
https://youtube.com/vishalshelke99
https://instagram.com/vishal_stagram
Liposomes
Sub :- Novel Drug Delievery Systems, Sterile Products Formulation & Technology
M.Pharm Sem II
Savitribai Phule Pune University
Introduction :-
Liposomes are vesicular structures composed of a lipid bilayer. These vesicular structures can be used as a vehicle for administration of nutrients and drugs.
Liposomes are concentric bilayered vesicles in which an aqueous volume is entirely enclosed by a membranous lipid bilayer.
Liposomes consist of Cholesterol, Phospholipid and drug molecule
Classification of Liposomes :-
Small Unilamellar (SUV) [20-100nm]
Medium Unilamellar (MUV)
Large Unilamellar (LUV) [>100nm]
Giant Unilamellar (GUV) [>1μm]
Multi Lamellar Vesicles (MLV) [0.5nm]
Oligolamellar Vesicles (OLV)
Multi Vesicular (MV) [>1μm]
ADVANTAGES
Provides selective passive targeting to tumor tissues.
Increased efficacy and therapeutic index.
Increased stability via encapsulation.
Reduction in toxicity of the encapsulated agents.
Improved pharmacokinetic effects (reduced elimination, increased circulation life times).
DISADVANTAGES
low solubility
short half life
high production cost
less stability
leakage and fusion of encapsulated drug
sometimes the phospholipid layer undergoes oxidation and hydrolysis reaction
Methods of Preparation of Liposomes
1 Mechanical Dispersion Method
Lipid film hydration by
hand shaken MLVs
Micro emulsification
Sonication
French pressure cell
Dried reconstituted vesicles
Membrane Extrusion Method
2 Solvent Dispersion Method
Ethanol injection
Ether injection
Double emulsion vesicles
Reverse phase
evaporation vesicles
3 Detergent Removal Method
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Global launch of the Healthy Ageing and Prevention Index 2nd wave – alongside...ILC- UK
The Healthy Ageing and Prevention Index is an online tool created by ILC that ranks countries on six metrics including, life span, health span, work span, income, environmental performance, and happiness. The Index helps us understand how well countries have adapted to longevity and inform decision makers on what must be done to maximise the economic benefits that comes with living well for longer.
Alongside the 77th World Health Assembly in Geneva on 28 May 2024, we launched the second version of our Index, allowing us to track progress and give new insights into what needs to be done to keep populations healthier for longer.
The speakers included:
Professor Orazio Schillaci, Minister of Health, Italy
Dr Hans Groth, Chairman of the Board, World Demographic & Ageing Forum
Professor Ilona Kickbusch, Founder and Chair, Global Health Centre, Geneva Graduate Institute and co-chair, World Health Summit Council
Dr Natasha Azzopardi Muscat, Director, Country Health Policies and Systems Division, World Health Organisation EURO
Dr Marta Lomazzi, Executive Manager, World Federation of Public Health Associations
Dr Shyam Bishen, Head, Centre for Health and Healthcare and Member of the Executive Committee, World Economic Forum
Dr Karin Tegmark Wisell, Director General, Public Health Agency of Sweden
CHAPTER 1 SEMESTER V PREVENTIVE-PEDIATRICS.pdfSachin Sharma
This content provides an overview of preventive pediatrics. It defines preventive pediatrics as preventing disease and promoting children's physical, mental, and social well-being to achieve positive health. It discusses antenatal, postnatal, and social preventive pediatrics. It also covers various child health programs like immunization, breastfeeding, ICDS, and the roles of organizations like WHO, UNICEF, and nurses in preventive pediatrics.
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Defecation
Normal defecation begins with movement in the left colon, moving stool toward the anus. When stool reaches the rectum, the distention causes relaxation of the internal sphincter and an awareness of the need to defecate. At the time of defecation, the external sphincter relaxes, and abdominal muscles contract, increasing intrarectal pressure and forcing the stool out
The Valsalva maneuver exerts pressure to expel faeces through a voluntary contraction of the abdominal muscles while maintaining forced expiration against a closed airway. Patients with cardiovascular disease, glaucoma, increased intracranial pressure, or a new surgical wound are at greater risk for cardiac dysrhythmias and elevated blood pressure with the Valsalva maneuver and need to avoid straining to pass the stool.
Normal defecation is painless, resulting in passage of soft, formed stool
CONSTIPATION
Constipation is a symptom, not a disease. Improper diet, reduced fluid intake, lack of exercise, and certain medications can cause constipation. For example, patients receiving opiates for pain after surgery often require a stool softener or laxative to prevent constipation. The signs of constipation include infrequent bowel movements (less than every 3 days), difficulty passing stools, excessive straining, inability to defecate at will, and hard feaces
IMPACTION
Fecal impaction results from unrelieved constipation. It is a collection of hardened feces wedged in the rectum that a person cannot expel. In cases of severe impaction the mass extends up into the sigmoid colon.
DIARRHEA
Diarrhea is an increase in the number of stools and the passage of liquid, unformed feces. It is associated with disorders affecting digestion, absorption, and secretion in the GI tract. Intestinal contents pass through the small and large intestine too quickly to allow for the usual absorption of fluid and nutrients. Irritation within the colon results in increased mucus secretion. As a result, feces become watery, and the patient is unable to control the urge to defecate. Normally an anal bag is safe and effective in long-term treatment of patients with fecal incontinence at home, in hospice, or in the hospital. Fecal incontinence is expensive and a potentially dangerous condition in terms of contamination and risk of skin ulceration
HEMORRHOIDS
Hemorrhoids are dilated, engorged veins in the lining of the rectum. They are either external or internal.
FLATULENCE
As gas accumulates in the lumen of the intestines, the bowel wall stretches and distends (flatulence). It is a common cause of abdominal fullness, pain, and cramping. Normally intestinal gas escapes through the mouth (belching) or the anus (passing of flatus)
FECAL INCONTINENCE
Fecal incontinence is the inability to control passage of feces and gas from the anus. Incontinence harms a patient’s body image
PREPARATION AND GIVING OF LAXATIVESACCORDING TO POTTER AND PERRY,
An enema is the instillation of a solution into the rectum and sig
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The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
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Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
1. Liposomes- A Novel
Drug Delivery System
From – Miss Snehal K. Dhobale
M-Pharm ( Pharmaceutics)
2. What are Liposomes???
• Liposomes are concentric bilayered vesicles in
which an aqueous core is entirely enclosed by a
membranous lipid bilayer mainly composed of
natural or synthetic phospholipids.
• Size range: 25nm-5000nm
• Liposomes consist of Cholesterol, Phospholipid
and drug molecule.
2
3. A simple view of liposomes
“Liposomes are microscopic
spheres made from fatty materials,
predominantly phospholipids.
“made up of one or more
concentric lipid bilayers, and range
in size from 50 nanometers to
several micrometers in diameter
3
4. Advantages with liposomes
Suitable for delivery of hydrophobic, hydrophilic
and amphipatic drugs and agents
Liposomes increases efficacy and therapeutic
index of drug (actinomycin-D)
Liposome increased stability via encapsulation
Suitable for controlled release
Suitable to give localized action in particular
tissues.
Suitable to administer via various routes
Liposomes help reduce the exposure of sensitive
4
tissues to toxic drugs
5. 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. 5
6. Components of liposomes
The structural components of liposomes
include:
A. Phospholipids
B. cholesterol
7. PHOSPHOLIPID
• Major component of biological cell membrane
Phospholipid
Hydrophobic
tail
2 fatty acid
chain containing
10-20 carbon
atoms
0-6 double bond
in each chain
Hydrophillic
head or polar
head
Phosphoric acid
bound to water
soluble
molecule
7
9. Phosphatidylcholine PC
• The most common
phospholipid use is
phosphatidylcholine PC
• Phosphatidylcholine is
amphipathic molecule
containing
i. A hydrophillic polar head
group phosphocholine
ii. A glycerol bridge
iii. A pair of hydrophobic
acyl hydrocarbon chain
9
10. Cholesterol:
• Incorporation of sterols in liposome bilayer can bring about
major changes in the preparation of these membranes.
• Cholesterol does not by itself form bilayer structure,but
can be incorporated into phospholipid membranes in very
high concentration unto 1:1 or even 2:1 molar ratios of PC.
• Cholesterol incorporation increases the separation
between the cholin head groups and eliminates the normal
electrostatic and hydrogen-bonding interactions.
10
11. Role of cholesterol in bilayer formation:
Cholesterol act as fluidity buffer
After intercalation with phospholipid molecules
alter the freedom of motion of carbon molecules in
the acyl Chain
Restricts the transformations of trans to gauche
Conformations.
Incorporated into phospholipid membrane upto
1:1 or 2:1 of cholesterol to PC.
11
12. Preparation of Liposomes
• Mechanism of Vesicle Formation
A. The budding theory
B. The bilayer phospholipids theory
12
13. The budding theory
– Stress induced hydration of phospholipids
– Organization in to lamellar arrays
– Results in to budding of lipid bilayer leading
to down sizing
SUV OLV
13
14. The bilayer phospholipids theory
• Liposomes are formed when thin lipid films are hydrated
• The hydrated lipid sheets detach during agitation and self-close
to form large, multilamellar vesicles (LMV)
14
15. Modes of liposomes/cell interaction
1.
Endocytosis
2. Adsorption
3. fusion 4. Lipid
transfer
15
16. Factors affecting release of drug
• Solvents
• pH
• Temperature
• Agitation
• Enzymes
• Cell culture
• Volume
Drug release from liposomes
• The lipid bilayer of the
liposome can fuse with
other bilayers (e.g. cell
membrane) thus
delivering the liposome
contents.
16
17. CLASSIFICATION OF LIPOSOMES
Structure
Method of
preparation
Composition
and application
Conventional
liposome
Speciality
liposome
17
18. 1. Classification of liposomes based on Structure
Unilamellar (UV)-all size range
Small Unilamellar(SUV) [20-100nm]
Medium Unilamellar (MUV)
Large Unilamellar (LUV) [>100nm]
Giant Unilamellar (GUV) [>1μm]
Multi Lamellar Vesicles (MLV) [0.5nm]
Oligolamellar Vesicles (OLV)
Multi Vesicular (MV) [>1μm] 18
19. 2. Classification of liposomes Based on Method of Preparation
Single or oligo lamellar vesicle made by reverse phase evaporation method (REV’s)
Multi lamellar vesicle made by reverse phase evaporation method (MLV-REV
Stable pluri lamellar vesicle (SPLV)
Frozen and thawed multi lamellar vesicle (FATMLV)
Vesicle prepared by extrusion technique (VET)
Dehydration- Rehydration method (DRV)
Dehydration- Rehydration method (DRV)
19
20. 3. Classification of liposomes Based on Composition and Application
Type of liposome Abbreviation Composition
Conventional liposome CL Neutral of negatively charge phospholipids and cholesterol
Fusogenic liposome RSVE Reconstituted sendai virus enveops
pH sensitive liposomes - Phospholipids such as PER or DOPE
Cationic liposome - Cationic lipid with DOPE
Long circulatory liposome LCL Neutral high temp, cholesterol and 5-10% PEG, DSP
Immune liposome IL CL or LCL with attached monoclonal antibody or recognition
sequences
20
21. 4. Classification of Liposomes Based Upon
Conventional Liposome
1). Stabilize natural lecithin (PC)
mixtures
2). Synthetic identical, chain
phospholipids
3). Glycolipids containing
liposome
21
22. 5.)Classification of Liposomes based upon Speciality
5.)
Liposomes
Bipolar Fatty Acids
Antibody directed Liposome
Methyl/Methylene x- linked liposome
Lipoprotein coated liposome
Carbohydrate coated liposome
Muiltiple Encapsulated Liposome
22
23. Methods of liposome preparation
Passive loading techniques Active loading techniques
Mechanical disp
ersion
methods
Solvent dispersi
on
methods
Detergent
removal
technique
LIPID FILM HYDRATION
BY HAND SHAKING,
FREEZE DRYING
NON HAND SHAKING
MICRO
EMULSIFICATION
SONICATION
FRENCH PRESSURE
CELL
MEMBRANE EXTRUSON
DRIED RECONSTITUTED
VESICLES
ETHANOL
INJECTION
ETHER INJECTION
DOUBLE EMULSION
REVERSE PHASE
EVAPORATION
1. Detergent removal
from mixed vesicles by
DIALYSIS
Column
Chromatography
DILUTION
24. General Method Of Liposome Preparation
1
• Cholesterol + Lecithin + Charge and Dissolve
in organic solvent
2
• Drying down lipid from organic solvent( Vaccum )
• Dispersion of lipid in aqueous media (Hydration
3
• Purification of resultant Liposomes
• Analysis of final product
24
25. 1. Mechanical dispersion method
Lipid dissolve in organic solvent/co-solvent
Remove organic solvent under vacuum
Film deposition
Solid lipid mixture is hydrated by using aqueous buffer
Lipid spontaneously swell & Hydrate
Liposome
25
26. 1) Lipid Hydration Method
A.) By hand shaking method
vesiculate to
form Multi
lamellar
vesicles(MLVs)
Upon
hydration
lipids swell
and peel out
from RB flask
Then film is
treated with
aqueous
medium
Lipids form
stacks of
film from
organic
solution
26
27. 1) Lipid Hydration Method
B.) NON-HAND SHAKING METHOD
The procedure differs
from hand shaken
method wherein it
uses a stream of
nitrogen to provide
agitation rather than
rotationary
movements.
Here the lipid film is
exposed to water
saturated nitrogen for
15-20 min
Milky suspension centrifugation
LUV
27
28. 1) Lipid Hydration Method
C.) FREEZE DRYING
• Another method of dispersing the lipid in a finely divided form,
prior to addition of aqueous media, is to freeze dry the lipid
dissolved in a suitable organic solvent.
• The solvent choice depends on the freeze point which needs to
above the temperature of the condenser lyophilizers. Tertiary
butanol is considered to be most ideal solvent.
• After obtaining the dry lipid which is an expanded foam like
structure, water or saline can be added with rapid mixing above
the phase transition temperature to give MLVs.
28
29. 2.) MICRO EMULSIFICATION
• This method is provided
for preparing small lipid
vesicles in commercial
quantities by
microemulsifying lipid
compositions using very
high shear forces
generated in a
homogenizing apparatus
operated at high
pressures at a selected
temperature.
• At least 20 circulations
(approximately 10
minutes) but not greater
than 200 circulations
(100 minutes) are
sufficient to produce a
micro emulsion of small
vesicles suitable for
biological application.
29
30. 3.) SONICATION
a)Probe sonication
The tip of a sonicator is directly
engrossed into the liposome dispersion.
The energy input into lipid dispersion is
very high in this method.
The coupling of energy at the tip results
in local hotness; therefore, the vessel
must be engrossed into a water/ice
bath.
b)Bath sonication
The liposome dispersion in a cylinder is
placed into a bath sonicator.
Controlling the temperature of the lipid
dispersion is usually easier in this
method, in contrast to sonication by
dispersal directly using the tip.
30
31. 4.) FRENCH PRESSURE CELL
• The method involves the
extrusion of MLV at 20,000 psi at
4°C through a small orifice.
• The method has several
advantages over sonication
method.
• The method is simple rapid,
reproducible and involves gentle
handling of unstable materials.
• The resulting liposomes are
somewhat larger than sonicated
SUVs.
• The drawbacks of the method
are that the temperature is
difficult to achieve and the
working volumes are relatively
small (about 50 mL maximum).
31
32. 5.) MEMBRANE EXTRUSON
Liposomes passed through membrane of defined pore size.
Lower pressure is required (<100 psi).
LUVs as well as MLVs can be processed.
Vesicle contents are exchanged with dispersion medium during
breaking and resealing of phospholipid bilayers as they pass
through the polycarbonate membrane.
For high entrapment, the water soluble compounds should be
present in suspending medium during the extrusion process.
32
33. 6.) DRIED RECONSTITUTED VESICLES
SUV’s in SUV’s with
DRV
Freeze dried
aqueous
solute to be
membrane
phase
entrapped
Solutes with
oligo and uni
lamellar
Freeze membranes
drying Rehydration
33
35. 1.) Ethanol Injection Method
• A lipid solution of ethanol is
rapidly injected to a vast
excess of buffer. The MLVs
are immediately formed.
• The drawbacks of the method
are that the population is
heterogeneous (30-110 nm),
liposomes are very dilute, it is
difficult to remove all ethanol
because it forms azeotrope
with water and the possibility
of various biologically active
macromolecules to inactivation
in the presence of even low
amounts of ethanol.
35
36. 2.) Ether Infusion Method
• A solution of lipids dissolved
in diethyl ether or
ether/methanol mixture is
slowly injected to an
aqueous solution of the
material to be encapsulated
at 55-65°C or under reduced
pressure.
• The subsequent removal of
ether under vacuum leads to
the formation of liposomes.
• This method is used to treat
sensitive lipids very gently.
36
37. Double emulsification
• In this process, an active ingredient is first dissolved in an
aqueous phase (w1) which is then emulsified in an organic
solvent of a polymer to make a primary w1/o emulsion.
• This primary emulsion is further mixed in an emulsifier-containing
aqueous solution (w2) to make a w1/o/w2
double emulsion.
• The removal of the solvent leaves microspheres in the
aqueous continuous phase, making it possible to collect
them by filtering or centrifuging.
37
38. 3.) Reverse-phase evaporation
Lipid organic solvent and
aqueous solution are
i. mixed,
ii. sonicated,
iii. formation of w/o
emulsion,
iv. evaporate to remove
the organic solvent
Lipids form a phospholipid
bilayer on vigorous
shaking , water droplets
collapse and formation of
LUV’s takes place. 38
39. Reverse phase evaporation technique.
Lipid in solvent
solution
Two-phase system Water in oil
emulsion
Gel formation Solvent removal
REV liposomes
Conti…
39
40. C. Detergent removal method
• The micellar dispersion is then subjected to
one of the following methods to remove the
detergent:
I. DIALYSIS :- Detergents with high CMC
(10-20 mM ) are used so that their removal
is facilitated e.g. bile salts- sodium cholate
and sodium deoxycholate , or synthetic
detergents like octileglucoside .
II. COLUMN CHROMATOGRAPHY :- By
passing dispersion over a Sephadex G-25
column. 40
41. i.) Dialysis Method
Dialysis is the simplest
procedure used for the removal
of the unbound drug, except
when macromolecular
compounds are involved
Advantages:
Dialysis Technique requiring
no complicated or expensive
equipment.
Dialysis is effective in
removing nearly all of the free
drug with a sufficient number
of changes of the dialyzing
medium 41
42. ii.) Column Chromatography
• Phospholipid in the form of either
sonicated vesicle or as a dry film, at a
molar ratio of 2:1 with deoxycholate form
unilamellar vesicles of 100nm on removal
of deoxycholate by column
chromatography
42
43. B. Active loading technique
AFTER DRYING IN PROCESS
FILM/CAKE OF LIPID IS FROM
STACKS OF LIPID
BILAYER FORM
SWELLING IN FLUID
SHEET IS SELF CLOSE
LOADING OF DRUG
ON pH- GRADIENT TECHNIQUE
FORMATION OF BILAYER
(LIPOSOMES) IF DRUG
Two steps process generates this pH imbalance
and active (remote) loading.
1) Vesicles are prepared in low pH solution, thus
generating low pH within the liposomal interiors
2) followed by addition of the base to
extraliposomal medium.
Basic compounds, carrying amino groups are
relatively lipophipic at high pH and hydrophilic at
low pH.
43
44. 1.) Lyophilization
• Freeze-drying (lyophilization) involves the removal of water from
products in the frozen state at extremely low pressures.
• The process is generally used to dry products and are thermo labile
and would be destroyed by heat-drying.
• The technique has a great potential as a method to solve long term
stability problems with respect to liposomal stability.
• It is exposed that leakage of entrapped materials may take place
during the process of freeze- drying and on reconstitution.
44
45. 2.) Pro-liposomes:
lipid Dried
over
lipid
Finely divided
particulate
support like
powdered
NACL/ sorbital
To increase the surface area of dried lipid film and to facilitate continuous
hydration and lipid is dried over the finally divided particulate support i.e.-
NaCl, Sorbitol, or other polysaccharides. These dried lipid coated
particulates are called as proliposomes
Proliposomes form dispersion of MLVs on addition of water, where support
is rapidly dissolved and lipid film hydrate to form MLVs
45
46. Uses of liposomes
• Chelation therapy for treatment of heavy metal poisoning
• Enzyme replacement
• Diagnostic imaging of tumors
• Study of membranes
• In gene delivery.
• As drug delivery carriers.
• Enzyme replacement therapy.
• Liposomes in antiviral/anti microbial therapy.
• In multi drug resistance.
• In tumour therapy.
• In immunology.
• In cosmetology
46
47. Applications
• Liposomes are successfully used to entrap anticancer
drugs. This increases circulation life time, protects from
metabolic degradation.
1.Cancer chemotherapy
• Steroids used for arthritis can be incorporated into large
MLVs.
• Alteration in blood glucose levels in diabetic animals was
obtained by oral administration of liposome encapsulated
insulin.
2.Liposomes as carrier of drug
in oral treatment
• Drugs like triamcilone, methotrexate, benzocaine,
corticosteroids etc can be successfully incorporated as
topical liposome
3.Liposomes for topical
applications
4. Liposomes for pulmonary
delivery
Inhalational devices like nebulizers are use to
produce an aerosol of droplets containing
liposomes.
47
48. 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
48
50. Liposomes could serve as tumor specific vehicles
(even without special targeting)
Liposomes better penetrate into tissues with disrupted endothelial lining
50
51. Characterization of liposomes
• Shape, size and its distribution
• Surface charge
• Percentage drug entrapment
• Entrapped volume
• Lamellarity
• Phase behavior of liposome
• Percentage drug release
51
52. References
1) ‘Controlled and Novel Drug Delivery’, “JAIN N.K.’’, CBS Publisher And
Distributors.Page No.307-321.
2) ‘Targeted and controlled drug delivery, Novel carrier Systems’ , “VYAS S.P.
and KHAR R.K.’’, CBS Publishers Page no.181 -195.
3) A.Chonn,P.R.Cullis,“Recent advances in liposome technologies and their
applications for systemic gene delivery”,Advanced Drug Delivery Reviews
4) Liposomes preparation methods by Mohammad riaz ,Pakistan Journal of
Pharmaceutical Sciences Vol.19(1), January 1996, pp.65-77
5) Liposome- as drug carriers-International Journal of Pharmacy & life sciences-
Himanshu Anwekar*, Sitasharan Patel and A.K Singhai
6) http://www.avantilipids.com
7) http://www. Mssm.edu/medicine/thrombosis/phosphol.html
8) Garrett, R. and Grisham C. Biochemistry, 2nd ed. Saunders Colleges
Publishing. New York (1999). 264
9) "Liposomes." www.collabo.com/liposom0.htm
10) Sharma Vijay K1*, Liposomes: Present Prospective and Future
Challenges,International Journal Of Current Pharmaceutical Review And
Research, oct 2010,vol1, issue 2,6-16
11) Himanshu Anwekar*, Liposome- as drug carriers, International Journal Of
Pharmacy & Life Sciences, Vol.2, Issue 7: July: 2011, 945-951 52