Prepared by:

Potdar Santosh

PE/2014/312

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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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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.

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Liposome

=Phospholipid+

cholesterolHydrophillic head

Hydrophobi

c tail

Components of liposomes:

The structural components of liposomes include:

A. Phospholipids

B. Cholesterol

A. Phospholipids:

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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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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.

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:

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).

Internalization

• Interact with target cells in various ways and promote the intracellular delivery of drug molecules.

CURRENT TRENDS IN LIPOSOME

Antibody-mediated liposome targeting

Long-circulating liposomes

Transferrin-mediated liposome targeting

Folate-mediated liposome targeting

pH-sensitive liposomes

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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.

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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.

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.

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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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:

1/21/2015 17European Patent, international publication No. WO2014159760A1

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Woodle, Martin C., and Danilo D. Lasic. "Sterically stabilized liposomes."Biochimica et Biophysica

Acta (BBA)-Reviews on Biomembranes 1113.2 (1992): 171-199.

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

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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Conclusion :

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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 :

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