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Vesicles
A careful look at the process of self organization in amphiphilic molecules
tells us that there are three geometric factors that determine
the structure formed and their sizes.
They are
- area of the molecule -(A)
- volume of their hydrocarbon chain -(V)
- the maximum length of the chains -(L)
The crucial combination of these parameters is (V/A*L) .
- If the value (V/A*L) is < 1/3 then spherical miscelles form.
- If 1/2 < (V/A*L) < 1 then bilayers are formed.
Here we shall consider the regime where 1/2 < (V/A*L) < 1
-the bilayer forming regime. The molecules that form
bilayers are mainly those with large hydrocarbon chains that are
too bulky to fit into smaller structures like micelles. A quick look
at the values of (V/A*L) for different structures shows that for the same
head-group and maximum length of the chains , molecules with double the
volume of the hydrocarbon chain form bilayers.
Thus molecules with two hydrocarbon chains are likely to form bilayers.
The most important class of bilayer forming molecules are
phospholipids.
In some cases it becomes energetically favorable for the
bilayer to form closed spherical structures rather than very long planar
structures.
These closed spherical bilayers are called vesicles
Note: If (V/A*L) > 1 then usually inverted micellar structures
form or the molecules precipitate out of the solution
(e.g cholesterol).
Vesicles (unilamellar - single bilayer) are a particular case from the
family of spherically concentric multilamellar (many bilayers) structures
called liposomes.
The properties of liposomes in addition to the general properties of
surfactants that make them useful for different applications are ..
- varying permeability of the bilayer to different molecules.
- ability to entrap substances and deliver them into desired
environments.
The size, lamellarity (unilamellar or multilamellar) and lipid composition of the bilayers influence many
of the important properties like the fluidity, permeability, stability and
structure -these can be controlled and customized to serve specific needs.
The properties are also influenced by external parameters like the
temperature and the presence of certain molecules nearby. The presence of
proteins in the biological membranes influences their properties e.g improves
the mechanical properties.
proteins and other molecules interacting with a liposome.
from D D Lasic - Liposomes - Elseiver
The shapes and shape fluctuation of large unilammelar vesicles is
dependent on the number of molecules in the two monolayers forming the
bilayer (under the reasonable assumption there is no transfer of lipid
molecules between the two monolayers). The sum of the number of molecules
influences the surface area of the vesicle and the difference in the number of
molecules determines the volume of the structure. Larger differences result in
smaller volume structures being formed e.g. cylindrical structures. For
monolayers with roughly the same number of molecules - stable spherical
structure are formed which have minimal bending energy and
maximal enclosed volume (recollect the argument that a sphere is the
geometrical configuration that has maximum volume for a given surface area.)
Applications in Pharmacological and Medicine :
- Liposomes as a drug delivery system:
- The use of most drugs is a compromise between the efficiency of the
drug and its unwanted side effects.
The drug delivery system can change the release pattern of drugs
in vivo, altering the effect the drugs would otherwise produce.Hence with
the use of an appropriate delivery system an increased efficiency
and a simultaneous reduction in unwanted side effects in drugs
can be achieved.
In addition to the above mentioned uses liposomes as a drug
delivery system offers some strong advantages
like biocompatibility and degradation
without any toxic
byproducts. (Remember : lipid molecules - the material that liposomes are the
made of are also the building blocks of living cells).
Liposomes can be administered intravenously, orally or intramuscularly
permitting flexibility as required - this is an advantage over some
other drug delivery systems.
Liposomes act as drug delivery systems by trapping the drug
within their interior hence creating a barrier between the drug and the
external environment - this process is often referred to as
microencapsulation. With an appropriate choice of liposome the
diffusion rate and dissolution of the material in the core to the external
medium can be controlled as required hence achieving controlled delivery.
There arises the possibility of using effective drugs which
have not been used for the lack of an appropriate delivery system as well as
completely novel drugs. For example drugs which are not very soluble in the
blood stream and consequently do not get carried by the bloodstream to
different
parts of the body can be encapsulated within a liposome and hence made more
soluble resulting in better transport or drugs which have toxic
effects but otherwise are effective .
Also some drugs which cannot be taken now because they are acted upon
before reaching the required site can be encapsulated and hence prevent
the 'action' on them. For example there are some drugs that get broken down by
the enzymes of the digestive tract and therefore liposomal encapsulation
would help protect the drug while in the digestive tract but would
release the drug once it got into the bloodstream .
The ultimate aim of drug delivery -the "magic bullet" concept envisages
the capacity to deliver drugs specifically to the required target cells - this
would result in high efficiency and near elimination of any unwanted side
effects .
It is important to mention that careful thought is required in choosing an
appropriate liposome in order to
get the desired use of them as drug delivery systems - as liposomes
are sensitive to external parameters like temperature, pH of the system and
interactions with various substances present in the system
they are injected into .
- Liposomes in medical imaging.
- Liposomes are used for improved contrast in CT scans for detection of
tumors in the liver and spleen which are natural targets for liposomes. They
are also used for similar purposes in MRI.
- Liposomes in anticancer therapy.
- The main aim of liposome encapsulation is to reduce the toxicity, achieve
systematic or localized sustained release, site avoidance and
tumor targeting.
Liposomes in the containment of oil pollution
-
In the case of oil spills on water the oil tends to spread on water
- this is due to significantly higher oil -water interfacial tension as
compared to the air -oil interfacial tension.
Due to their ability to reduce the oil-water interfacial tension
liposomes are effective in stopping the spreading of oil on the surface of
water. The oil forms condensed, unspreadable droplets which can
subsequently be removed mechanically, skimmed or absorbed.
Thus making the whole process of cleaning up much more efficient and
manageable. In the case of oil (or other hydrophobic liquid wastes)
spread on soil the reduction in
surface tension allows
oil droplets to detach from the minerals in the soil and exit through
the capillaries in the soil.
Liposomes also increase both the number and variety of microorganisms that
can get to the
oil surface and hence facilitate quicker biodegradation of the oil.
This is true for oil contamination both on land and on water.
Other industries
- Food industry: as an emulsifier for the preparation of
bread. It is important to get proper mixing of ingredients
in order to get the bread to rise and bake properly. The addition of
emulsifiers help in obtaining a good mixture.
The addition of emulsifiers also help in the control of
flavor, texture and other qualities in food products ranging from
mayonaise to chocolates .
Liposomes are useful in improved control and shortening of fermentation
time e.g in cheese making and brewing beer.
- Cosmetic industry: They are used in cosmetics formulations
for their ability to dissolve simultaneously both
water-soluble and water-insoluble substances. Now water-insoluble
compounds can be dissolved in a bio-compatible and bio-degradable
lipid-water system without any organic solvents. Additionally
they are used as an active ingredient in many skin care lotions and
sun-screen products.
Liposomes are valuable for regeneraion of the skin and resupply of lipid
molecules (of which liposomes are made) and moisture. They help improve
skin elasticity and 'barrier function' which are major causes for
skin aging.
- There are many other industries where liposomes play important
roles including:
- plastic industry
- pesticides
- paints (most paints are emulsions)
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