Topics Covered
Background
Liposomes
Why are
Liposomes Used?
What Are
Current Applications of Liposomes?
Why are The Size of
Liposomes Important?
What
Determines the Behaviour of Liposomes in the Human Body?
How are the Sizes of
Liposomes Measured?
Advantages
of Photon Correlation Spectroscopy (PCS)
Applications of Size and Zeta
Potential
Liposomes in
Gene Therapy
Background
Size largely determines the sites of action
of liposomes Zeta potential measurement enables the factors affecting size
to be investigated.
Liposomes
What are Liposomes? They are simply vesicles
or ‘bags’ in which an aqueous volume is entirely enclosed by a membrane composed
of lipid (fat) molecules, usually phospholipids.
These spontaneously form when lipids are
dispersed in water.
Why are Liposomes
Used?
They can be used to entrap materials such as
drugs both within the central aqueous compartment if they are water soluble, or
within the membrane if they are oil soluble.
In addition the surface can be modified to
‘target the liposome’.
What Are Current Applications
of Liposomes?
Current applications of liposomes
include:
-
As vehicles to deliver drugs to specific
parts of the body e.g. Ambiosome®, an antifungal drug (liposomal amphotericin
B)
- To allow much smaller doses of drug to be
used to reduce side effects
-
In cosmetics as "antiwrinkle" agents
- Currently being studied for use in gene
therapy
- To effectively target to various bacteria
and enhance the inhibition of bacterial growth compared to equal concentrations
of the free drug e.g. in toothpaste
Why are The Size of Liposomes
Important?
The sites of action of liposome-cell
interactions in the body are determined to a large extent by size:
- Small liposomes can pass through the
fenestrae of the liver sinusoids
- Intermediate sized liposomes are retained
within the blood compartment and can circulate for long periods.
- Larger liposomes rapidly taken up by
Kupffer cells
What Determines the
Behaviour of Liposomes in the Human Body?
The behaviour of liposomes in vivo is
determined by:
- Physical size
- Chemical composition
- Membrane permeability
- Quantity of entrapped solutes
How are the Sizes of Liposomes
Measured?
Two main methods are used for size
measurement in liposome research, electron microscopy and Photon Correlation
Spectroscopy
Advantages of Photon
Correlation Spectroscopy (PCS)
- PCS is a very rapid technique, typical
measurements taking between 2 and 5 minutes. With sample preparation, electron
microscopy will take much longer.
- Liposomes are measured in their natural
state, there are no problems of dehydration or staining required. Electron
microscopy requires the specialised freeze fracture technique.
- PCS measures the distribution of tens of
thousands of particles. EM would require hundreds of photographs to give
comparable statistics.
Applications of Size and
Zeta Potential
Zeta
potential is a fundamental tool used to investigate how size changes, as a
function of any parameter of the preparation.
- Monitor the effect of changing the
environment, e.g. pH, temperature, surfactant, blood serum, presence of
counterions, adsorption of proteins.
- Develop formulations that resist
aggregation/flocculation
- Measure the thickness of coatings on the
surface of the liposomes.
- Predict the effectiveness of the coating
of liposomes against opsonisation in vivo.
- Obtain information about whether the
active agent used is encapsulated or adsorbed on the surface.
Liposomes in Gene
Therapy
- Obtain information about DNA-liposome
interactions, DNA-peptide interactions and condensing of DNA for liposomal
encapsulation
- Follow the changes in size of
liposome-drug complexes as their ratio is altered
Source: “Biotechnology: The Characterisation and Use of
Liposomes”, Application Note by Malvern
Instruments.
For more information on this source please
visit Malvern
Instruments Ltd (UK) or Malvern Instruments
(USA).