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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