Liposomes

Liposomes

(Targeted
drug delivery systems)

Contents of this chapter

•         
Introduction to vesicular systems

•         
Types of vesicular systems

–         
Liposomes

–         
Niosomes

–         
Transferosomes

–         
Ethosomes

–         
Virosomes

–         
Pharmacosomes

Session objectives

By the end of this session, students will be able to:

•       Explain  the concept of vesicular systems

•       Explain
the importance of liposomes and niosomes

•       Enlist
advantages and limitations of liposomes

•       Describe
different methods used for preparation of liposomes

Vesicular systems

•         
They are unique structures capable of entrapping
hydrophilic,  lipophilic, amphiphilic and
charged hydrophilic drugs

•         
If the proportion of water in increased, these
amphiphiles can  form one or more
concentric bilayers

•         
Hydrophilic drugs get entrapped in the internal
aqueous environment

•         
Amphiphilic , lipophillic drugs get entrapped in
the bilayered wall

Advantages of vesicular
systems

•       They
can encapsulate both hydrophilic and lipophilic moieties

•       Prolong
half-lives of drugs by increasing duration in systemic circulation due to encapsulation,

•       Ability
to target organs for drug delivery

•       Biodegradability

•       Lack
of toxicity

Liposomes

•       Liposomes
are concentric  bilayered vesicles

•       The
aqueous core is entirely  enclosed by a
membranous lipid  bilayer

•       Lipid
bilayer is composed of  natural or
synthetic phospholipids

•       First
produced in England in 1961 by Alec D. Bangham, who was studying
phospholipids and blood clotting

•       Size
of a liposome ranges from some 20 nm up to  several micrometers

•       Phospholipids
are amphipathic moieties with a  hydrophilic
head group and two hydrophobic tails

Structural Components of
Liposomes

The Main Components  of
Liposomes are:

1. Phospholipids
2. Cholesterol

Classification of liposomes

On the basis of their size and number of bilayers, liposomes
are classified as:

(1)    Multilamellar
vesicles (MLV)

(2)    Unilamellar
vesicles

Unilamellar vesicles can also be classified into 2
categories:

(1)    Large
unilamellar vesicles (LUV) (>100nm)

(2)    Small
unilamellar vesicles (SUV)(20-100nm)

Methods of preparation

All the methods of preparing the liposomes involve four basic
stages:

1. Drying
   down lipids from organic solvent
2. Dispersing
   the lipid in aqueous media
3. Purifying
   the resultant liposome
4. Analyzing
   the final product

The following methods are used for the preparation of
liposomes:

1. Passive loading techniques- loading
   of the  entrapped agents before or
   during the manufacturing  procedure
2. Active loading technique – compounds
   with  ionizable groups, and those
   which display both lipid and water 
   solubility, can be introduced into the liposomes after the  formation of intact vesicles (remote
   loading)

Passive loading techniques

Include three different methods:

1. Mechanical
   dispersion method
2. Solvent
   dispersion method
3. Detergent
   removal method (removal of non-encapsulated  material)

A. Mechanical Dispersion Methods

The following are types of mechanical dispersion methods:

1. Sonication
2. French
   pressure cell: extrusion
3. Freeze-thaw
   sonication
4. Lipid
   film hydration by hand shaking, non-hand. shaking or freeze drying
5. Micro-emulsification
6. Membrane
   extrusion
7. Dried
   reconstituted vesicles

1. Sonication

There are two sonication techniques:

•       Probe
sonication and Bath sonication

•       Sonication
is the act of applying sound energy to agitate  particles in a sample

•       Ultrasonic
frequencies (>20 kHz) are usually used

2. French pressure cell:
extrusion

•       Reduces
the particle size of  liposomes using
high shear force

•       Pressure
of about 20,000 psi at  4⁰C

•       Passing
the dispersion through  the French press
results in a  progressive decrease in
the  mean particle diameter

•       Approximately
95% of the vesicles can be converted to SUVs (30-50)nm

•       Liposomes
produced by this method are more stable than 
those produced by sonication

3. Freeze thaw sonication method

Summary

• The
  methods used for preparing the liposomes involve four basic stages: Drying
  down lipids from organic solvent, 
  Dispersing the lipid in aqueous media ,Purifying the  resultant liposome
• The
  preparation of liposomes are Passive and Active loading techniques

• Passive
  loading technique Includes Mechanical dispersion,  Solvent dispersion and Detergent removal
  method

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