Novel Drug Delivery System liposomes Basic Understanding and Concepts

Novel Drug Delivery System liposomes
Concepts
Overview
Classification
Types
Uses
Advantages
Disadvantages

1. LIPOSOMES

2. Introduction

3. LIPOSOME:Thenameliposomeisderivedfromtwo
Greekwords'Lipid'meaningfatand'Soma'meaning
body.
Discovery:LiposomeswerefirstdescribedbyBritish
hematologistDr.AlecDin1961
Definition: A liposome is a spherical vesicle in which
aqueous volume is entirely enclosed by a membrane
composed of lipid molecule.
Liposome can be composed of naturally-derived
phospholipids with mixed lipid chains (like egg
phosphatidylethanolamine).
Liposome can be used as drug carriers and loaded
with a great variety of molecules, such as small drug
molecules, proteins, nucleotides and even plasmids.

4. STRUCTURAL COMPONENTS
PHOSPHOLIPIDS
CHOLESTEROL
AQOUES VOLUME

6. ROUTES OF ADMINISTRATION :
Liposomes can be administered
Parenterally
Topically
Via Inhalation
Current products are administered Parenterally
CONFIGURATIONS :
Spheres
Cylinder

7. REASONSFORUSINGLIPOSOMES
Tounderstandhowliposomescanbestbeusedto
improvetheperformanceoftheencloseddrug,itmaybe
usefultoconsiderthefollowingbasicreasonsforusing
liposomesasadrugcarrier.
1.Direction.
2.Duration
3.Protection
4.Internalization
5.Amplification

8. PROPERTIES OF LIPOSOMES
1. For medical applications as drug carriers the liposomes
can be injected intravenously and when they are
modified with lipids which render their surface more
hydrophilic, their circulation time in the bloodstream can
be increased significantly. Such so called "stealth"
liposomes are especially being used as carriers for
hydrophilic (water soluble) anticancer drugs like
doxorubicin, mitoxantrone and others.
2. To further improve the specific binding properties of a
drug-carrying liposome to a target cell, -such as a tumor
cell -, specific molecules (antibodies, proteins, peptides
etc.) are attached on their surface

9. ADVANTAGES
1.Liposomes encapsulated drugs are delivered
intact to various tissues and cells and can be
released when the liposomes are destroyed,
enabling site specific and targeted drug delivery.
2.Liposomes can be used for both hydrophilic and
lipophilic drugs without the need for chemical
modification .
3.Other tissues and cells of the body are protected
from the drug until it is released by liposomes thus
decreasing drug toxicity
4.the size , charge and other characteristics can be
altered depending upon the drug and its use.

10. 5. Liposomes are biocompatible, completely
biodegradable, non-toxic, flexible and
nonimmunogenic for systemic and non-systemic
administrations.
6. Liposomes can be formulated as a suspension,
as an aerosol, or in a semisolid form such as
gel, cream and lotion, as a dry vesicular powder
(proliposome) for reconstitution or they can be
administered through most routes of
administration including ocular, pulmonary,
nasal, oral, intramuscular, subcutaneous, topical
and intravenous.
7. Liposomes could encapsulate not only small
molecules but also macromolecules like
haemoglobin, erythropoietin, interleukin-2 and
interferon.

11. 8. Liposomes increase stability of entrapped
drug via encapsulation. (Amphotericin B,
Taxol)
9. Liposomes increase efficacy and therapeutic
index of drug (Actinomycin-D).
10. Alter the pharmacokinetic and
pharmacodynamic property of drugs
(reduced elimination, increased circulation
life time)
11. Flexibility to couple with site-specific
ligands to achieve active targeting
(Anticancer and Antimicrobial drugs).

12. DISADVANTAGES
Disadvantages of liposomes include their
tendency to be taken up by cells and the
slow release of the Drug when the
liposomes are taken up phagocytes
through Endocytosis , Fusion , surface
adsorption or Lipid exchange

15. Both water soluble and water insoluble
drugs may be incorporated.
Processing method effect :-
•Particle size
•Percentage drug entrapment
•Stability
•Release rate

16. Processing methods
For hydrophobic drugs:-
•Extrusion
•Ultrasonication
•Micro fluidization

17. For hydrophilic drugs:-
–Reverse phase
–Freeze thaw

18. Handling
of
Liposome's

74. Quality control assays of liposomal formulation

75. MODES OF DRUG
RELEASE FROM
LIPOSOME

76. Liposome can interact with cells by four
different mechanisms:-
•Endocytosis by phagocytic cells
•Adsorption to cell surface
•Fusion with plasma cell
•Transfer of liposomal lipids to cellular or
sub cellular membrane or vise versa

77. PURIFICATION OF LIPOSOMES
•Three tecniques are used for purification
namely;
•Gel filteration column chromatogaphy
•Dialysis
•Centrifugation

78. APPLICATIONS
In
bioengeering
In gene
therapy
In
medical
In cosmetics
In agro-food
industry
Oral drug delievry
In pharmaceutics
In basic
science
others
APPLICATIONS
In
bioengeering
In gene
therapy
In
medical
In cosmetics
In agro-food
industry
Oral drug delievry
In pharmaceutics
In basic
science
others

79. APPLICATION IN
BIOENGINEERING:
•As transportation factor for nucleic acid in
form of phospholipids
•There are two ways of delivery:
1. as endocytosis enhancer
2. phosphate precipitation

80. APPLICATION IN
GENETHERAPY:
•Liposomes use to deliver nondefective gene
into apr cell
•E.g pt with cystic fibrosis
•In recent exp inhalation copies of human
genes mixed with liposomes,70% of cells
lining the lungs of mice incorporate genes and
began to make proteins

81. APPLICATION IN BASIC SCIENCES:
DISCIPLIN
E
APPLICATION
MathematicsTopology of 2 dimentional surfaces in three
dimentional space
Physics Aggregation of behaviours ,fractals
BiophysicsPermeability , photophysics etc
Chemistry Photochemistry , Atrifacial photosynthesis , catalysis
Biology Model biological membranes , cell function , fusion
Pharmaceuti
cs
Studies of dreug action
BiochemistryReconstituion of membrane protuens into atrifacial
membrane

82. APPLICATIONS IN MEDICAL
/PHARMACEUTICAL INDUSTRY:
LIPOSOME
UTILITY
CURRENT APPLICATION DISEASE STATE
SolublizationAmphoteracin B , Minoxidil Fungal Infection
Site AvoidanceAmphoteracin B,doxrubicin Fungal infection,cancer
Sustain
realease
Systemic antineoplastic
drugs,hormones,corticosteroids
Cancer,biotherapeutics
RES targetingInflammations,vaccines Cancer,tropicals
Specific
targeting
Cell bearing specific antigensWide therapeutic
applications
ExtravasationLeaking vasculature in
cancer,inflammation
Cancer,bacterial infection
Accumulationprostaglandins Cardiovascular diseases
Enhanced
penetratio
n
Topical vehicals dermatology

83. APPLICATIONS IN
MEDICAL/PHARMACEUTICAL
INDUSTRY ARE AS FOLOWS:
•In cancer chemotherapy
•In diabetes
•In ophthalmology
•In parasitic diseases/infections
•Lysosomal storage diseases
•Metal storage diseases

84. •In pulmonary drug delivery
•As carrier of vaccines
•In topical preparation
•In ophthalmic delivery
•other

85. •In cancer chemotherapy:
•Cell specific drugs
•Increase circulation life time
•Potential metabolic degradation
•Alter tissue distribution

86. •APPLICATION INDIABETES:
•Increase uptake ofmacromolecules
•APPLICATION IN PARASITIC
DISEASES:
•In Leishmaniasis:
•Decrease the dose needed
•Deposite conjugates at kuffer cells

87. IN ORAL DRUG DELIVERY
SYSTEM:
•These are limited due to lipomicidal
enviroment in GIT
•Intragastrial adm of free or encapsulated
liposome not made
•Liposome compose of multilayers,encap in
biodegradeable gells ,polymer coated
liposomes etc are use

88. Storage diseases:
In Gaucher’s disease
•Deliver enzymes to lysosomal system
Metal storage disease
•In these diseases inability to cross cell
membrane
•By liposomes it is desireable to increase
entrapement of chelators in liposomes

89. In pulmonary delivery/lungs
disease:
•Size of liposomes ranges from 20nm-
>1micrometer
•Used as aerosoles i.e nebuliszers
•Examples:
1.Cytosin arabinoside
Free Ara-C was rapidly absorbed into the systemic
circulation whilst liposomal encapsulated drug
remained within lungs for a considerable
time,hence reduces adverse effects in other
tissues.
2.Antioxident enzymes

90. In pulmonary delivery/lungs
disease:
•Size of liposomes ranges from 20nm-
>1micrometer
•Used as aerosoles i.e nebuliszers
•Examples:
1.Cytosin arabinoside
Free Ara-C was rapidly absorbed into the systemic
circulation whilst liposomal encapsulated drug
remained within lungs for a considerable
time,hence reduces adverse effects in other
tissues.
2.Antioxident enzymes

91. As carrier of vaccines:
A.As immunolposomes:
Limitations:
•Extravasation
•Strictly stabilised liposomes by surface grafted
hydrophilic polymers
B. As carrier of antigens:
•Limitations:
•Steps to retard uptake
1.Minimize rate of uptake by RES by using small
neutral or unilamellar liposomes.

92. 2.By coating surface of liposomes.
3.By coupling appropriate molecules.
Examples:
1.Cholera toxins
Toxicity was completely eliminated and
antigenecity was enhanced when CT attached to
liposomes.
2.Herpes simplex virus type-I antigens
Enhanced immunogenecity with liposomal antigen.

93. In topical preparations:
•Increase penetration of lipid and drug molecule
in skin.
•Provide local delivery.
Examples:
1.Procain cream
Shows long lasting anesthesia whereas procain cream
was ineffective.
2.Diclofenac gel
Increase conc. In subcutaneous tissue as well
as increase permeation through the skin.

94. In ophthalmic delivery:
•Used because of completely
biodegradable and relatively non toxic.
•In treatment of acute and chronic herpetic
keratitis.
•Use in liquid and semisolid vesicles.
•Use to incorporate penicillin G
,Indoxol,Carbachol.

95. Liposome as Radiodiagnostic
Carriers
•Liposomes are used in different imaging
modalities to locate the sites specifically.
Their radiodioagnostic applications include
liver, brain and spleen imaging, lymphatic
imaging, tumor imaging, blood pool
imaging, visualization of inflammation and
infection sites, visualization of bone
marrow and eye vasculature and imaging
cardiovascular pathologies.

96. Other medical applications:
•Diagnostic purposes.
•In inflammatory diseases.
•In arthritic joints.
•In lungs disorders.
•To treat neonatal jaundice.

97. Applications in cosmetics:
•Use for delivery of ingredients of
cosmetics
•Acts as antiageing agent because
liposomes are well hydrated
•Acts as a supply to replenish lipids i.e
lanoleic acid
•In addition to natural lipids liposomes can
be made from synthetic lipids
•Enhance permeability in skin

98. In agro food industory:
•Ability of liposomes to solubilize
•As sequester compounds
•As release incorporated molecule
•Use in fermentation processes as encapsulated
enzymes i.e cheese fermentation
•Act as preservatives
•Some liposomes are tried in shellfish farms
•Liposomes encapsulated biocides have
superior action due to prolonged presence of
fungicides,herbicides or pesticides

99. Other applications of liposomes:
In paints:
•Self healing paints
•Water based paints
In ecology:
•In oil spills as encapsulated bacteria improves
degradation rates of hydrocarbon
•As surfactants to improve coagulation and
sinking of oil spread and cleaning
Liposomes containing anchored chelators:
•To clean toxic and radioactive metals from
solutions