Liposomes-- The artificial cells

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Liposomes are uni / multi- lamellar phospholipids vesicles composed of concentric spherical layers of aqueous zones sandwiched between phospholipid membranes. These are sometimes referred to as "artificial cells" since they are analogous both in morphology and its physiology to natural cells.[1]

CHEMICAL UNITS: [2]
* The main chemical constituents of liposomes are phospholipids and cholesterol moieties.

Phospholipids:

?In aqueous phase they orient themselves in a bilayered sheet such that their hydrophilic phase orients towards aqueous phase and hydrophobic portion of each of the fatty chains attaches to each other. Finally, in order to minimize the unfavorable interactions the laminated sheets fold to form a spherical core.

?The commonly used phospholipids are
- Naturally occurring phospholipids:
1. Phopshatidylcholine (PC).
2. Phosphotidylethanol amine (PE).
3. Phosphotidylserine (PS).
- Synthethic phospholipids:
1. Dioleoylphosphatidylcholine (DOPC).
2. Distearoylphosphatidylcholine (DSPC).
3. Dioleoylphosphatidylethanolamine (DOPC).
4. Distearoylphosphatidylethanolamine (DSPE).

Cholesterol:

?The purpose of adding cholesterol is, it functions as a fluidity buffer i.e.. below the phase transition temperature it makes the membrane less ordered and increases the permeability; and above the phase transition temperature it makes the membrane more ordered and less permeable.

COMPARISON WITH OTHER DRUG CARRIERS: [3]


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Characteristics
Liposomal Drug Products
Dendrimers
Nanoemulsions
Polymeric Nanoparticles
Parenteral delivery
Possible
Possible
Possible
Possible
Oral delivery
Not Possible
Possible
Possible
Possible
Ability to deliver lipophilic
drugs
Yes
Yes
Yes
Yes
Ability to deliver hydrophilic
drugs
Yes
Yes
Yes
Yes
Physical Stability
+
++
+
+++
Biological Stability
+
++
+
+++
Biocompatibility
++
++
++
++
Ease of sterilization
++
++
++
++
Drug targeting
+++
+++
+
+++
Ease of commercialization
+
+
+
+
Ability to deliver Biotechnological
therapeutics
++
+
++
++
Regulatory acceptance
of excipients
++
++
++
++

+++: High; ++: Moderate; +: low


TYPES OF LIPOSMES: [4]

1. Conventional Liposomes
2. Stealth Liposomes.
3. Immuno- liposomes.
4. Charged Liposomes.

MANUFACTURING OF LIPOSOMAL DRUG PRODUCTS: [5]

1. Hydration Method: The lipids are dissolved in suitable organic solvent; these solvents are later removed by evaporation, vacuum drying or lyophillization. The dry lipid film/ paste or cake is then hydrated, resulting in the formation of large multilamellar vesicles; its size is reduced to the range of 100nm to 200nm,by homogenization or extrusion.
2. Emulsion Method: The solid phospholipids are dissolved in a suitable organic solvent and then added to aqueous medium with vigorous agitation, the organic solvent is removed under pressure and the resulting liposomal dispersion is homogenized.

Drug incorporation into the liposomal vesicles depends on the physical properties like solubility and partition coefficient. Water soluble drugs like doxorubicin, pencillin G etc are simply entrapped in the aqueous core and lipid soluble drugs (ex: Cyclosporine) will pass through the lipid layer. The acyl chains of the phospholipid bilayers provide a solubulizing environment for the drug molecules.
These liposomes can be formulated in the form of a suspension, aerosol, gel, cream or lotion or as a dry vesicular powder (proliposomes).

CHARACTERIZATION:


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Particle
size
Measured by particle size analyzer (laser
diffraction method)
Lamellarity
Measured by freeze electron microscopy technique.
Encapsulation efficiency
Determined by the formulae Entrapped efficiency
= amount of drug entrapped/ total amount of drug X 100
Surface charge
Determined by electrophoresis method


ADVANTAGES:

? Liposomes are biocompatible, biodegradable, non-immunogenic, and flexible.
? Liposomes can incorporate lipophillic or hydrophilic and amiphillic molecules of any size.
? Liposomes significantly alter the pharmacokinetic and pharmacodynamic properties of the drugs.

DISADVANTAGES:

? RES uptake
? Drug leakage problems.
? Poor stability in the blood.
? High product cost.

APPLICATIONS:

? Potential drug/ protein delivery vechiles
? Controlled and sustained release.
? Gene Delivery Ex: Lipofectin and Transfectase
? Dermatology and Cosmetology
? Radio-diagnostic carriers.

MARKETED PRODUCTS: [5]


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Marketed product
Drug used
Target diseases
Company
DoxilTM or CaelyxTM
Doxorubicin
Kaposi's sarcoma
SEQUUS, USA
DaunoXomeTM
Daunorubicin
Kaposi's sarcoma, breast
& lung cancer
NeXstar, USA
Fungizone(r)
Amphotericin-B
Fungal infections, Leishmaniasis
Bristol-squibb, Netherland
Topex-Br
Terbutaline sulphate
Asthma
Ozone, USA
Novasome(r)
Smallpox vaccine
Smallpox
Novavax, USA
Avian retrovirus vaccine
Killed avian retrovirus
Chicken pox
Vineland lab, USA
Epaxal -Berna
Vaccine
Inactivated hepatitis-A
Virions
Hepatitis A
Swiss serum & vaccine institute,
Switzerland
VincaXome
Vincristine
Solid Tumours
NeXstar, USA
Mikasome(r)
Amikacin
Bacterial infection
NeXstar, USA


STEALTH (PEGYLATED) LIPOSOMES: [6]

Stealth liposomes are surface modified liposomes in which PEG units are attached to the outer surface of liposome units, so that they can escape the opsonization effect in the blood, which is a major cause for decreased drug availability at its site of action. Pegylated liposomes are long- circulating with improved bioavailability and sustained action of loaded drug molecules.

MARKETED PRODUCTS:[6]

?ProgestGel(tm) - A liposomal form of progesterone and Vitamin K for postmenopausal women's health.
?ProBone-O Drops(tm) - A liposomal form of vitamin B12 and folic acid.
?PEGysomal CoQ10(tm) - Coenzyme Q10, a powerful antioxidant that supports cardiovascular health in particular.
?PEGysomal Idebenone(tm) - Idebenone is an analog of coenzyme Q10 that improves brain function.

CONCLUSIONS:

Liposomes are novel drug carriers with the unique property of being capable of incorporating a wide range of drug molecules. However significant improvements must be made in standardizing & optimizing methods of preparation and in enhancing the storage stability of products for greater commercial success of liposomes.

References:

1.Current status and future prospects of New Drug Delivery System; Pharma Times Vol-2- No.40- April 2010, by Dr. Subash, C. Mandal, and Dr. Moitreyee Mandal.
2.Vyas S. P., Dixit V., In: Advances in liposomal therapeutica, First Edition, CBS Publishers, New Delhi, 2001;1:230-243.
3.Novel Nanostructured lipidic Drug Delivery Systems by Bhupinder Singh et. Al. ; Pharma Review, Nov- Dec 2009; Pg no 118-122
4.http://www.pharmainfo.net/pharma-student-magazine/liposomes-emerging-fie... [Accessed on 28th July 2010]
5.http://www.pharmainfo.net/reviews/liposome-versatile-platform-targeted-d... [Accessed on 28th July 2010]
6.http://www.pharmainfo.net/reviews/review-pegylated-liposome-cancer-thera... [Accessed on 28th July 2010]

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About the Author

Santosh kumar. JH's picture

Key Skills:-

Lean Methodology

Six Sigma Expertise

Formulation Operations

Comments

kranthi kumar's picture

Dear santosh, Its a wide range of collection. Keep up the good work.
Santosh kumar. JH's picture

Thanks for your appreciation.. Keep sending your words...
Ravi Vamsi's picture

can u sugeest some points regarding the other types of liposomes ????
Santosh kumar. JH's picture

Based on Structural Parameters liposomes are: 1. Multilamellar vesicles (>0.5 micrometer) 2. Oligolamellar vesicles (0.1-1 micrometer) 3. Unilamellar vesicles (all size ranges) 4. Multi vesicular vesicles (>1 micrometer) Based on Composition and Applications: 1. pH sensitive liposomes 2. Cationic liposomes others as mentioned previously 3. Long (shealted) circulatory liposomes 4. Immunoliposomes Thank You!
Uma Pratyusha's picture

Dear Santosh, Very good one and very colorful! What is RES uptake that you have mentioned in the disadvantages of liposomes?

Regards

Uma Prathyusha

Santosh kumar. JH's picture

Dear Uma, RES means Reticulo- Endothelial System: This includes various phagocytic cells, these phagocytic cells as a part of body's defense mechanism they passively entrap various foreign materials and cells; since liposomes are almost similar to cells these are entrapped by these phagocytes a phenomenon popularly known as opsonization. This reduces the total available drug content (bio availability); in order to avoid this we are surface modifying the liposomes with a polymer like PEG (Polyethylene Glycol)-- Stealth Liposomes this repels the phagocytes and are there are not opsonized.

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