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1. Liposomes
1

2. OUTLINE
• WHAT ARE LIPOSOMES?
• BASIC LIPOSOME STRUCTURE.
• WHY USE LIPOSOMES IN DRUG
DELIVERY?
• ADVANTAGES OF LIPOSOMES.
• STRUCTURAL COMPONENTS OF
LIPOSOMES.
• CLASSIFICATION OF LIPOSOMES.
• PREPARATION OF LIPOSOMES.
2

3. Liposomes (= vesicles)
 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 were first produced in England in
1961 by Alec D. Bangham, who was
studying phospholipids and blood clotting.
 The size of a liposome ranges from some
20 nm up to several micrometers. 3

4.  The lipid moecules are ususally phospholipids- amphipathic moieties with a
hydrophilic head group and two hydrophobic tails.
 On addition of excess water, such lipidic moieties spontaneously originate to give
the most thermodynamically stable conformation.
 In which polor head groups face outwords into the aqueous medium, and the lipidic
chains turns inwords to avoid the water phase, giving rise to double layer or bilayer

5. Hydrophobic
Hydrophilic
cavity
5

6. Basic liposome structure
6

7. What is a lamella?
– A Lamella is a flat plate like structure that appears
during the formation of liposomes. The phospholipids
bilayer first exists as a lamella before getting
converted into spheres.
– Several lamella of phospholipids bilayers
are stacked
one on top of the other during formation of liposomes
to form a multilamellar structure.
7

8. Unilamellar vesicles Multilamellar vesicles
8

9. Structural Components of
Liposomes
• THE MAIN COMPONENTS OF LIPOSOMES ARE :-
1. Phospholipids
2. Cholesterol
9

10. Phospholipids
• Phospholipids are the major structural compone
nts of biological membranes such as the
cell membrane.
Phosphoglycerides
Two Types Of
Two Types Of
Phospholipids(Along With
Phospholipids(Along With
Their Hydrolysis Products)
Their Hydrolysis Products)
Sphingolipids
10

11. Phosphatidylcholine
• Most common phospholipids used is
phosphatidylcholine (PC).
• Phosphatidylcholine is an amphipathic
molecule in which exists:-
– a hydrophilic polar head group,
phosphocholine.
– a glycerol bridge.
– a pair of hydrophobic acyl hydrocarbon
chains.
11

12. Generally phospholipids are
represented as follows:-
follows:
12

13. Phospholipids
Polar Head Groups
Three carbon glycerol
13

14. 14

15. ROLE OF CHOLESTEROL IN BILAYER FORMATION
• Cholesterol by itself does not form bilayer structure.
• 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
• Cholesterol incorporation increases the separation between
choline head group & eliminates normal electrostatic &
hydrogen bonding interactions

16. Some other commonly used
phospholipids
 Naturally occurring phospholipids:
– PC : Phosphatidylcholine
– PE : Phosphatidylethanolamine
– PS : Phosphatidylserine
 Synthetic phospholipids:
– DOPC : Dioleoylphosphatidylcholine
– DSPC : Distearoylphosphatidylcholine
16

17. Why Use Liposomes in Drug
Delivery?
Drug Targeting
nactive: Unmodified liposomes gather in specific tissue
reticuloendothelial system
Active: alter liposome surface with ligand (antibodies,
enzymes, protein A, sugars)
Physical: temperature or pH sensitive liposomes
Directly to site
17

18. Why Use Liposomes in
Drug Delivery?
Pharmacokinetics - efficacy and toxicity
Changes the absorbance and biodistribution
Deliver drug in desired form
Multidrug resistance
Protection
Decrease harmful side effects
Change where drug accumulates in the body
Protects drug
18

19. Why Use Liposomes in
Drug Delivery?
Release
Affect the time in which the drug is released
Prolong time -increase duration of action and
decrease administration
Dependent on drug and liposome properties
Liposome composition, pH and osmotic gradient, and
environment
19

20. ADVANTAGES OF LIPOSOMES
• Provides selective passive targeting to tumor
tissues.
• Increased efficacy and therapeutic index.
• Increased stability of encapsulated drug.
• Reduction in toxicity of the encapsulated agent.
• Site avoidance effect (avoids non-target tissues).
• Improved pharmacokinetic effects (reduced
elimination increased circulation life times).
• Flexibility to couple with site specific ligands to
achieve active targetting.
20

21. DISADVANTAGES
 PHYSICAL/ CHEMICAL STABILITY
 VERY HIGH PRODUTION COST
 DRUG LEAKEGE/ ENTRAPMENT/ DRUG FUSION
STERILIZATION
 SHORT BIOLOGICAL ACTIVITY / t ½
 OXIDATION OF BILAYER …LIPIDS AND LOW SOLUBILITY
 RATE OF RELEASE and ALTERED BIODISTRIBUTION
 LOW THEARAPEUTIC INDEX and DOSE EFFECTIVENESS
 OVERCOMING RESISTANCE
 EXTENCIVE CLINICAL AND LABORATORY RESEARCH TO
ACERTAIN LONG CERCULATING LIPOSOMES
REPEATED IV ADMINISTRATION PROBLEMES

22. CLASSIFICATION OF LIPOSOMES
• Liposomes are classified on the basis of
– Structural parameters
– Method of preparation
– Composition and applications
22

23. 1. Based on structural parameters
Based on structural parameters
MLV OLV MVV
UV Unilamellar
Multilamellar oligolamellar Multivesicular
Vesicles (all
Large vesicles vesicles
size ranges)
vesicles (>0.1-1.0 um) (> 1.0 um)
(>0.5 um)
SUV Small Unilamellar
MUV Medium Unilamellar
Vesicles
Vesicles
20-100nm
LUV Large Unilamellar
GUV Giant Unilamellar Vesicles
Vesicles
>1um
>100nm 23

24. 24

25. 25

26. 3. Based on composition & application
1- Conventional.
2- Stealth.(PEG, increase
blood circulation time and
decrease phagocytic
attack).
3- Cationic.(lipoplex)
4- Targeted.(antibody)
26

27. PREPARATION OF LIPOSOMES
Methods of liposome
preparation
Active or remote loading:
certain types of compounds with
Passive loading: ionisable groups
Involves loading of the
and those with both
entrapped
manufacturing procedure
agents before or during the
lipid and water solubility can be
manufacturing procedure
introduced into the liposomes
after the
formation of the intact vesicles27

28. Methods of liposome preparation
Passive loading techniques Active loading techniques
Mechanical dispersion Solvent dispersion Detergent removal
methods methods methods
Detergent(Cholate,
Lipid film hydration by Ethanol injection
Alkyl glycoside,
hand shaking non-hand Ether injection
Triton X-100) removal
shaking and freeze drying Double emulsion
Micro emulsification from mixed micelles by
vesicles
Sonication Stable plurilamellar Dialysis
French pressure cell Vesicles Column
Membrane extrusion Reverse phase chromatography
Dried reconstituted evaporation vesicles Dilution
vesicles Reconstituted sendai
Freeze thawed liposomes virus enveloped
vesicles 28

29. BASIC METHOD OF FORMULATION OF LIPOSOMES
SOLVANT
eg.CHCl3
LIPID e.g..
LICITHIN
DISPERSION
FORMATIONN
Separate liposome's from
supernatatant by
Encapsulated solute centrifugation, gel
filtration/ sonication or
FILM OF LIPID dialysis or by addition of
OCCURS AT SIDES buffers + drug.
OF VESSELS

30. Method Vesicles
Mechanical methods
Vortex or hand shaking of phospholipid dispersions MLV
Extrusion through polycarbonate filters at low or medium
OLV, LUV
pressure
Extrusion through a French press cell “Microfluidizer”
Mainly SUV
technique
High-pressure homogenization Mainly SUV
Ultrasonic irritation SUV of minimal size
Bubbling of gas BSV
Methods based on replacement of organic solvent(s) by aqueous media
Removal of organic solvent(s) MLV, OLV, SUV
Use of water-immiscible solvents: ether and petroleum MLV, OLV, LUV
Ethanol injection method LUV
Ether infusion (solvent vaporization) LUV, OLV, MLV
Reverse-phase evaporation
Methods based on detergent removal
Gel exclusion chromatography SUV
“Slow” dialysis LUV, OLV, MLV
Fast dilution LUV, OLV
Other related techniques MLV, OLV, LUV, SUV

31. PASSIVE LOADING TECHNIQUES
• Mechanical Dispersion method
• Solvent Dispersion method
• Detergent Solubilisation method

32. MECHANICAL DISPERSION
METHODS

33. LIPID HYDRATION METHOD
The mechanical energy required for swelling of lipids and dispersion
of casted lipid film is imparted by manual agitation (hand shaking
technique)
The % encapsulation efficiency as high as 30% is achieved due to
loss of water soluble component during swelling and entrapped only
10-15%. On other hand lipid soluble drug encapsulated 100%

34. 1. Hand‐shaken multilamellar vesicles
2. Non‐shaking vesicles
3. Pro‐liposomes
4. Freeze drying
:–AFTER THESE METHODS, OTHER PROCESSING METHODS ARE
USED TO MODIFY THESE TYPE OF VESICLES THAT ARE
PRODUCED SUCH AS:
• Micro emulsification liposomes (MEL)
• Sonicated unilamellar vesicles (SUVs)
• French Pressure Cell Liposomes
• Membrane extrusion liposomes
• Dried‐reconstituted vesicles (DRVs)
• Freeze thaw Sonication (FTS)
• pH induced vesiculation
• Calcium induced fusion
:–These methods are known as “the mechanical treatment of MLVs” or
“Processing of lipids by physical means
34

35. Hand shaken multilamellar vesicles
• Simplest and most widely used method of physical dispersion
• Basic method involves
– Dissolution of the lipid mixture and charge components in
chloroform:methanol solvent
– Evaporation of the solvent in a rotary evaporator or by hand
shaking to form a film shaking to form a
– Further drying of the film by attaching the flask to the
manifold of the lyophilizer.
– Casted film is then dispersed in an aqueous medium.
– Upon hydration, lipid swell and peel off the wall of the flask
and vesiculate forming multilamellar vesicles (MLVs)
35

36. PROCESS IN MORE DETAIL –
STEP 1:
• Lipid mixture of different phospholipids and charge components in
chloroform:methanol solvent mixture (2:1 v/v) is prepared first and
then introduced into a round bottom flask with a ground glass neck.
• This flask is then attached to a rotary evaporator and rotated at 60
rpm.
• The organic solvents are evaporated at about 30 degrees Celsius or
above the transition temperature of the lipids used.
• The rotation is continued for 15 mins after the dry residue first
appears.
• The evaporator is isolated from the vacuum source by closing the
tap.
• The nitrogen is introduced into the evaporator and the pressure at
the cylinder head is gradually raised till there is no difference
between inside and outside the flask between inside and outside the
flask.
• The flask is then removed from the evaporator and fixed on to the
manifold of lyophilizer to remove residual solvents. 36

37. STEP 2‐ Hydration of lipid layer:
• After releasing the vacuum and removal from the lyophilizer,
the flask is flushed with nitrogen.
• 5ml of saline phosphate buffer (containing solute to be
entrapped) is added.
• The flask is attached to the evaporator again (flushed with N2)
and rotated at room temperature and pressure at the same
speed or below 60 rpm.
• The flask is left rotating for 30 minutes or until all lipid has
been removed from the wall of the flask and has given
homogenous milky‐white suspension free of visible particles.
• The suspension is allowed to stand for a further 2 hours at
room temperature or at a temperature above the transition
temperature of the lipid in order to complete the swelling
process to give MLVs.
37

38. Hand shaken method in general
38

39. Non‐shaking vesicles
• The procedure differs from hand shaken method in that it uses a stream
of nitrogen to provide agitation rather than the rotationary movements.
• Solution of lipid in chloroform:methanol mixture is spread over the flat
bottom conical flask.
• The solution is evaporated at room temperature by flow of nitrogen
through the flask without disturbing the solution.
• After drying, water saturated nitrogen is passed through the flask until
the opacity of the dried lipid film disappears (15-20mins).
• After hydration, lipid is swelled by addition of bulk fluid. The flask is
inclined to one side, 10‐20 ml of 0.2M sucrose in distilled water
(degassed) is introduced down the side of the flask, and the flask is
slowly returned to upright orientation.
• The fluid is allowed to run gently over the lipid layer on the bottom of the
flask.
• The flask is flushed with nitrogen sealed and allowed to stand for 2 hrs
at 37 degrees Celsius. Take care not to disturb the flask in any way.
• After swelling, the vesicles are harvested by swirling the contents of the
flask gently , to yield a milky‐suspension. 39

40. PROLIPOSOMES
 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
 Methods overcome the stability problem and entrapment
efficiency doesn’t matter when formation of stable
liposome.

41. 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.
41

42. SONICATION METHOD
PROBE SONICATOR: is employed for
dispersions, which require high energy in a
small volume (e.g., high concentration of
lipids, or a viscous aqueous phase)
Disadvantage- lipid degradation due to high
energy and sonication tips release titanium
particles into liposome dispersion
BATH SONICATOR: The bath is more
suitable for large volumes of diluted lipids.
Method: Placing a test tube containing the
dispersion in a bath sonicator and sonicating
for 5-10min(1,00,000g) which yield a
slightly hazy transparent solution. Using
centrifugation to yield a clear SUV
dispersion

43. FRENCH PRESSURE CELL
LIPOSOMES
This techniques yields rather “uni or
oligo lamellar liposomes” of intermediate
size of 30-80 nm in diameter depending on
the applied pressure.
Dispersion of MLVs can be converted to
SUVs by passage through a small orifice
under high pressure.
MLV dispersion are placed in the French
pressure cell and extruded at about
20,000psi at 450C By multiple extrusion
i.e.., 4.5 passed about 95% of MLVs get
converted into SUVs which can be
determined by size exclusion
chromatography.

44. MICRO EMULSIFICATION LIPOSOMES(MEL)
“Micro Fluidizer” is used to prepare small MLVs from Concentrated lipid
dispersion
The lipids can introduced into fluidizers, either as a dispersion of large MLVs
or as a slurry of unhydrated lipids in organic medium.
Microfluidizer pumps the fluid at very high pressure(10,000psi, 600-700 bar)
through a 5um orifice.
Then it is forced along defined micro channels, which direct two streams of
fluid to collide together at right angles at a very high velocity, thereby affecting
an efficient transfercanenergy.
The fluid collected of be recycled through the
pump and interaction chamber until vesicles of
the spherical dimension are obtained.
After a single pass, the size of vesicles is reduced
to a size 0.1 and 0.2um in diameter.

45. VESICLES PREPARED BY
EXTRUSION TECHNIQUES (VETs)
It is used to process LUVs as well as MLVs.
Liposomes prepared by this tech. are called
as membrane filter extrusion liposomes
The 30% capture volume can be obtained
using high lipid conc. The trapped volume
in this process is 1-2 litre /mole of lipids
 It is due to their ease of production, readily
selectable vesicle diameter, batch to batch
reproducibility & freedom from solvent or
surfactant contamination is possible

46. FREEZE THAW SONICATION
METHOD (FTS)
The method is based on
freezing of a unilamellar
dispersion & then thawing at
room temp for 15 min.
Thus the process ruptures &
refuses SUVs during which the
solute equilibrates between
inside & outside & liposomes
themselves fuse & increase in
size.
Entrapment volume can be
upto 30% of the total vol. of
dispersion. Sucrose, divalent
metal ions & high ionic
strength salt solutions can not
be entrapped efficiently

47. SOLVENT DISPERSION
METHODS
Note:- Organic solvent miscible with aqueous
phase

48. SOLVENT DISPERSION METHODS FOR
PASSIVE LOADING

49. Ethanol injection:-
• An ethanol solution of lipids is injected rapidly through a fine
needle into an excess of saline or other aq. medium
• This method has low risk of degradation of sensitive lipids
• The vesicles of 100 nm size may be obtained by varying the conc.
Of lipid in ethanol or by changing the rate of injection of ethanol
solution in preheated aqu. solution.
• Limitation-solubility of lipids in ethanol & vol. of ethanol that
can be introduced into medium(7.5%v/v max)
• Difficulty to remove residual ethanol from phospholipid
membrane
Ether injection:-
• Involves mixing of organic phase into aqu. Phase at the temp. of
vaporizing the organic solvent
• It has low encapsulation efficiency

51. REVERSE PHASE EVAPORATION
METHOD

52. DETERGENT SOLUBILISATIOIN
METHODS
Note:- Liposome size and shape depend on chemical nature of detergent,
concentration and other lipid involved

53. Detergent depletion method
• The phospholipids are brought into intimate contact
with the aqueous phase via detergents which
associate with phospholipid molecules
• The structures formed are called as micelles
• The conc. of detergent at which micelles are formed is
called as CMC
• The detergent methods are not very efficient in %
entrapment values
• The methods employed for removal of detergent
include dialysis, column chromatography & use of
biobeads

54. Dialysis Method
Detergent commonly use for this purpose exhibit resonably
high CMC (10 to 20 mM) so that their removal is facilitated
A commercial version of the dialysis system is available under
the tradename LIPOREP
Column Chromatography
Phospholipid inthe 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
54

55. ACTIVE LOADING TECHNIQUES
AFTER DRYING IN PROCESS
• Weak amphipathic bases accumulate in the aqueous phase of lipid
vesicles in response to a difference in pH between the inside and
outside of the liposomes (pHin & pHout) FILM/CAKE OF LIPID IS FROM
• Two steps process generates this pH imbalance and active
(remote) loading.
• Vesicles are prapared in low pH solution, thus generating low pH
within the liposomal interiors, followed by addition of the base to
STACKS OF LIPID
extraliposomal medium.
BILAYER FORM
• Basic compounds, carrying amino groups are relatively lipophipic
at high pH and hydrophilic at low pH.
• In two chambered aqueous system separated by membrane
liposomes, accumulation occurs at the low pH side, under SWELLING IN FLUID
dynamic equilibrium conditions.
• Thus the unprotonated form of basic drug can diffuse through the
bilayer SHEET IS SELF CLOSE
• The exchange of external medium by gel chromatography with
neutral solution LOADING OF DRUG
• Weak base doxorubicine, adriamycin and vincristine which co- ON pH- GRADIENT TECHNIQUE
exist in aqueous solutions in neutral and charged forms have been
sucessfully loaded into preformed liposomes via the pH gradient FORMATION OF BILAYER
method. (LIPOSOMES) IF DRUG

56. 56

57. 57

58. 58

59.
Reverse phase evaporation vesicles
partial bilayer
In rotar y evaporator close to
each other
At this stage-
the monolayers come
close to each other
59

60. Ethanol/Ether injection method
60

61. DRYING
• An important step involved in the preparation of
liposomes is the drying of the lipid.
• Large volume of organic solution of lipids is most
easily dried in a rotary evaporator fitted with a dried a
rotary evaporator fitted with cooling coil and a
thermostatically controlled water bath.
• Rapid evaporation of solvent is carried out by gentle
warming (20‐40 degrees) under reduced pressure (400
700 mm Hg)(400‐700 mm Hg)
• Rapid rotation of the solvent containing flask increases
the surface area for evaporation.
61

62. • In cases where sufficient vacuum is not attainable or if
the concentration of lipids is particularly high, it may be
difficult to remove the last traces of chloroform from the
lipid film.
Therefore, it is recommended as a matter of routine that
after rotary evaporation, some further means is
employed to bring the residue to complete dryness.
Attachment of the flask to the manifold of lyophilizer, and
overnight exposure to high vacuum is a good method.
62

63. I] Physical Dispersion or
Mechanical Dispersion Methods
• Aqueous volume enclosed using this method is usually
5‐10%, which is very small proportion of the total volume
used for swelling.
• Therefore large quantity of water‐soluble compounds are
wasted during swelling.
• On the other hand, lipid soluble compounds can be
encapsulated to 100% efficacy, provided they are not
present in quantities that are greater than the structural
component of the membrane.
63

64. How LUVs Are Generated From The
Suspension?
• The suspension is centrifuged at 12,000g for 10
min. in a bench centrifuge at room temperature.
• The layer of multilamellar vesicles floating on the
surface is removed. To the remaining fluid an
equal volume of iso‐osmolar glucose is added
and centrifuged again at 12,000g. Large
unilamellar vesicles form a soft pellet which can
be resuspended in any required medium of
appropriate osmolarity.
64

65. Pro‐Liposomes
• Method devised to increase the surface of dry lipid while
keeping the low aqueous volume.
• In this method, the lipids are dried down to a finely divided
particulate support, such as powdered sodium particulate
support, such as powdered chloride, or sorbitol or other
polysaccharide – to give pro‐liposomes.
• The lipids are swelled upon adding water to dried lipid coated
powder (pro‐liposomes), where the support rapidly dissolves
to give a suspension of MLVs in aqueous solution.
• The size of the carrier influences the size and heterogeneity
of the liposomes.
65

66. • This method overcomes the problems encountered when
storing liposomes themselves in either liquid, dry or frozen
form, and is ideally suited for preparations where the material
to be entrapped incorporates into lipid membrane.
• In cases where 100% entrapment of aqueous component is
not essential this method is also of value .
• For preparing pro‐liposome a special equipment i.e. Buchi
rotary evaporator ‘R’ with water cooled condenser coil and a
stainless steel covered thermocouple connected to a digital
thermometer is required.
• The end of the glass solvent inlet tube is modified to ato fine
point, so that the solvent is introduced into the flask as a fine
spray.
66

67. BUCHI Rotary Evaporator R type
67

68. Method Of Preparation of Proliposomes
• The lipid solution in chloroform (60mg/ml) is prepared and sorbitol powder is
introduced into 100ml flask.
• The flask is then fitted into the evaporator and rotated slowly so that the
powder tumbles gently off the walls to ensure good mixing and the solvent is
evaporated.
• The flask is lowered into a water bath at 50‐55 degrees Celsius when a
good vacuum is developed.
• An aliquot of 5ml of lipid solution is introduced into the flask via the solvent
inlet tube.
• The solvent is absorbed completely by the powder and the temperature of
the bed is monitored.
• As evaporation proceeds the temperature will decrease.
• A second aliquot is introduced slowly when the temperature begins to rise
again.
• The temperature is allowed to rise to 30 degrees Celsius the vacuum is
released and the drying process is completed by connecting the flask
containing the powder to lyophilizer, and leaving it evacuated overnight at
room temperature.
• The powder is transferred into a 10ml glass vial containing 600mg solid
each (100mg lipid and 500mg sorbitol support) flushed with nitrogen, and 68
sealed well and stored.

69. Processing of the lipids hydrated
by physical means, or the mechanical
treatment of MLVs
• Micro emulsification liposomes (MEL)
• Sonicated unilamellar vesicles (SUVs)
• French Pressure Cell Liposomes
• Membrane extrusion liposomes
• Dried‐reconstituted vesicles (DRVs)
• Freeze thaw Sonication (FTS)
• pH induced vesiculation
• Calcium induced fusion
69

70. Micro emulsification liposomes (MEL)
70

71. Sonicated unilamellar vesicles (SUVs)
71

72. French Pressure Cell Liposomes
72

73. Membrane Extrusion Liposomes
73

74. Liposomes Help Improve
Therapeutic index
Rapid metabolism
Unfavorable pharmokinetics
Low solubility
Lack of stability
Irritation
74

75. Current liposomal drug
preparations
Type of Agents Examples
Anticancer Drugs Duanorubicin, Doxorubicin*, Epirubicin
Methotrexate, Cisplatin*, Cytarabin
Anti bacterial
Triclosan, Clindamycin hydrochloride,
Ampicillin, peperacillin, rifamicin
Antiviral
DNA material AZT
Enzymes cDNA - CFTR*
Radionuclide Hexosaminidase A
Fungicides Glucocerebrosidase, Peroxidase
Vaccines
In-111*, Tc-99m
Amphotericin B*
Malaria merozoite, Malaria sporozoite
Hepatitis B antigen, Rabies virus glycoprotein
75
*Currently in Clinical Trials or Approved for Clinical Use

76. CFTR
Gene Therapy
Deliver cDNA of Cystic Fibrosis Transmembrane Conductance
Regulator (CFTR) to epithelial tissue of respiratory system
Cationic liposome
Fuse to cell membrane and
incorporate cDNA into cell
Clinical trials - no significant
change in symptoms
Now trying adeno associated
virus 76

77. Doxil
Chemotherapy drug doxorubin
Anemia, damage to veins and tissue at injection, decrease
platelet and WBC count, toxic to
Treats Kaposi’s sarcoma lesions or cancer tumors
Modifications of liposome “stealth”
keeps doxorubin in blood for 50 hours instead of
20 minutes
concentrates at KS lesions and tumors
*Just approved by FDA* 77

78. Amphotericin B
Systemic fungal
infections in immune compromised patients
AmB - kills ergosterol-containing fungal cells, also
kills cholesterol-containing human cells
Side effects: nephrotoxicity, chills, and fevers
Fungizone - AmB with deoxycholate 78

79. Liposomal Formulation of AmB
Phospholipid:AmB ratio
AmB Cholesterol - only few %moles
Lipid
Exact Mechanism of liposomes not understood
Diffusion
Lipid transfer
Decrease in toxicity
79
No decrease in effectiveness of drug against fungi

80. Problems with Liposomal Preparations of Drugs
$$$$
Fungizone $40.58 Amphotec $2334
Doxil $1200 per treatment, twice the cost of normal protocol
of chemotherapy and drugs
)
Lack long term stability (short shelf life
Physical and chemical instability
Freeze dry and pH adjustment
Low “Pay Load” - poor encapsulation
Low “Pay Load” - poor encapsula
Polar drugs and drugs without opposite charge
Modifications
Possibility of new side effects
Doxil “hand and foot syndrome”
80

81. Future
Studies with insulin show that liposomes may
be an effective way to package proteins
and peptides for use
Clinical Trials for several liposomal formulations
More studies on the manipulation of liposomes
81

82. THANK YOU
82