2. Content:
1. Introduction
2. Structure Of Liposome
3. Reasons for using liposome as carriers
4. Current trends in liposome
5. Therapeutic application of Liposomes
6. Marketed liposomal products
7.Conclusion
8.References
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3. Introduction :
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Liposomes are artificially prepared spheres, consisting of
concentric phospholipids bilayers separated by aqueous
compartments.
Liposomes were first produced in England in1961 by
Alec D. Bangham.
5. Components of liposomes:
The structural components of liposomes include:
A. Phospholipids
B. Cholesterol
A. Phospholipids:
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6. Phospholipids :
1.Naturally occurring phospholipids used are :
PC: Phosphatidylcholine.
PE: Phosphatidylethanolamine.
PS: Phosphatidylserine
The most commonly used is phospatidylcholine (PC ).
2.Synthetic phospholipids used are:
DOPC: Dioleoyl phosphatidylcholine
DSPC: Disteroyl phosphatidylcholine
DOPE: Dioleoyl phosphatidylethanolamine
DSPE: Distearoyl phosphatidylethanolamine
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7. B. Cholesterol:
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1. Stabilizes the membrane.
2. Act as fluidity buffer.
3. Restricts the transformations of trans to cis or staggered to gauche
Conformations.
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Advantages of liposomes:
Provides selective passive targeting to tumor tissues.
(liposomal doxorubicin) .
Site avoidance effect (avoids non-target tissues).
Increased efficacy and therapeutic index.
Reduces toxicity .
Improved pharmacokinetic effects .
Couple with site-specific ligands to achieve
active targeting.
9. Production cost is high.
Leakage and fusion of encapsulated molecules.
Sometimes phospholipids undergoes oxidation and hydrolysis like
reaction.
Short half-life.
Low solubility.
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Disadvantages of liposomes:
10. Basic reasons for using liposomes as drug
carriers
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Direction:
• Target a drug to the intended site of action (drug targeting, site-specific delivery).
Duration
• Show sustained release process. Thus, an increased duration of action and a
decreased frequency of administration
Protection
• Drugs are protected against the action of detrimental factors (e.g.. degradative
enzymes).
Internaliz
ation
• Interact with target cells in various ways and promote the intracellular delivery of
drug molecules.
12. Evolution of liposomes. A Conventional Liposome
B Antibody-targeted immunoliposome with antibody covalently coupled (c) to the reactive
phospholipids in the membrane
C Long-circulating liposome grafted with a protective polymer (such as PEG)
D Long-circulating immunoliposome simultaneously bearing both
protective polymer and antibody.
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Torchilin, Vladimir P. "Recent advances with liposomes as pharmaceutical carriers." Nature reviews
Drug discovery 4.2 (2005): 145-160.
13. 1/21/2015 13
As folate receptors (FR) are frequently overexpressed in a wide
range of tumour cells.
Delivering ofliposomes into
living cells using FR endocytosis.
Liposomal doxorubicin have been
delivered into various
tumour cells through FR and
demonstrated increased cytotoxicity
show inceased survival rate.
1. Folate-mediated liposome targeting :
Pan, Xing Q., et al. "Strategy for the treatment of acute myelogenous leukemia based on folate receptor β–targeted
liposomal doxorubicin combined with receptor induction using all-trans retinoic acid." Blood 100.2 (2002): 594-602.
14. Long residence of liposome in the body is achieved by coating the
liposome surface with inert, biocompatible polymers, such as PEG, which form a
protective layer over the liposome surface and slow down liposome recognition by
opsonins and therefore subsequent clearance of liposomes.
It show dose-independent, non-saturable kinetics.
Increased bioavailability.
Increased action.
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2.Long-circulating liposomes
Yang, Chuang, Hai-Zhong Liu, and Zhong-Xue Fu. "Effects of PEG-liposomal oxaliplatin on apoptosis, and
expression of Cyclin A and Cyclin D1 in colorectal cancer cells." Oncology reports 28.3 (2012): 1006-1012.
15. 3.Antibody-mediated liposome targeting.
Liposome with specific antibodies capable of recognizing
various tumour cells through tumour-cell-surface-bound nucleosomes
improved targeting to tumour cells and increased its cytotoxicity.
Incresed target specific drug delivery and
reduced toxicity of cytotoxic drug.
Torchilin, Vladimir P. "Recent advances with liposomes as pharmaceutical carriers." Nature reviews
Drug discovery 4.2 (2005): 145-160.
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16. 4.pH-sensitive liposome :
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As tumour has low pH than normal cells hence we can
use pH sensitive release of liposome content, liposomes are constructed
from pH-sensitive components to release their contents into the
cytoplasm Of the tumour cell .
Transferrin receptors (TfR) are overexpressed on the
surface of many tumour cells, and so antibodies against TfR, as well
as Transferrin itself, are popular ligands for liposome targeting to
tumours and inside tumour cells.
5.Transferrin-mediated liposome targeting:
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18
Woodle, Martin C., and Danilo D. Lasic. "Sterically stabilized liposomes."Biochimica et Biophysica
Acta (BBA)-Reviews on Biomembranes 1113.2 (1992): 171-199.
19. Therapeutic application of Liposomes :
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1.Liposome in enzyme replacement therapy
2.Liposome in tumor therapy
increase effectiveness and decrease toxicity
carrier for small cytotoxic drug
3.Liposome in gene delivery
Gene and antisense delivery
Genetic (DNA) vaccination
4.Liposome in Immunology
20. 1.Liposomal doxorubicin(myocet)
Use: Combination therapy with
cyclophosphamide in metastatic breast cancer.
2.Liposomal daunorubicin(Daunoxome)
Use : HIV-related Kaposi’s sarcoma
3.Liposomal cytarabine(DepoCyt(e))
Use : treatment of lymphoma
Marketed liposomal products
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22. Torchilin, Vladimir P. "Recent advances with liposomes as pharmaceutical
carriers." Nature reviews Drug discovery 4.2 (2005): 145-160.
Yang, Chuang, Hai-Zhong Liu, and Zhong-Xue Fu. "Effects of PEG-
liposomal oxaliplatin on apoptosis, and expression of Cyclin A and Cyclin
D1 in colorectal cancer cells." Oncology reports 28.3 (2012): 1006-1012.
Pan, Xing Q., et al. "Strategy for the treatment of acute myelogenous
leukemia based on folate receptor β–targeted liposomal doxorubicin
combined with receptor induction using all-trans retinoic
acid." Blood 100.2 (2002): 594-602.
Woodle, Martin C., and Danilo D. Lasic. "Sterically stabilized
liposomes."Biochimica et Biophysica Acta (BBA)-Reviews on
Biomembranes 1113.2 (1992): 171-199.
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References :
