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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