Overview
Elastin is the protein that gives bodily tissues their elasticity.
It is particularly important in skin
where it imparts youthful suppleness and resilience. The Elastin
fibers help skin to maintain its tensile strength as well as
the ability to recoil after being stretched. It is therefore
important that the adequate levels of elastin are maintained.
Elastase is a protease that specifically degrades elastin.
It is always present in skin at low levels where it is needed
for growth, tissue repair and the natural slow elastin turnover
that takes place in healthy skin. It is also an important
component of the defense system and when skin is inflamed,
the levels of elastase can be seen to have increased dramatically.
The release of elastase during the natural cellular processes,
as well as during the aging process, contributes to the loss
of skin tone over time. As skin ages, the levels of elastase
increase to a point where elastin breaks down faster than
it can be made. This results in the dramatic loss of skin
elasticity.
Several pentacyclic triterpenoid metabolites of plant origin
are natural inhibitors of elastase. Application of these naturally
occurring compounds in vitro has shown them to be very effective
elastase inhibitors, combating age-related changes as well
as inflammation.
Study
The digestion of Extra-Cellular Matrix (ECM) takes place in
wells of a 24-well microplate. Each well contains 360 ng (12
pmol) of human neutrophil elastase and 36 ml of various dilutions
of the Pyrus Malus Extract (2%, 5%, 10%, 20%) in a total volume
of 1 ml Hanks salt solution. Digestion is allowed to proceed
for 2.5 hours. In the wells indicated by red bars, the enzyme
was added first, and the inhibitor was added 15 minutes later.
During this 15 minute period, the enzyme binds tightly to
the ECM and is resistant to inhibition by a number of other
protease inhibitors. In the wells indicated by the blue bars,
the inhibitor was added 15 minutes before the enzyme. Under
these conditions, the inhibitor competes with the ECM more
effectively for the enzyme and its apparent potency is enhanced.
We refer to the sequence of addition of enzyme first and inhibitor
second as the "therapeutic" mode, because it emulates
a scenario in which the inhibitor is added to an on-going
inflammatory reaction. We refer to the sequence of addition
of inhibitor first and enzyme second as the "prophylactic"
mode, because it emulates a scenario in which the inhibitor
is present prior to the onset of an inflammatory reaction.
The spontaneous release of radiolabeled proline as well as
the release mediated by the same concentration of neutrophil
elastase in the absence of any inhibitor are shown for comparison.
Liposomal Delivery
Overview of Liposomes
Liposomes are microscopic spherical vesicles that form when
phospholipids are hydrated. When mixed in water under low
shear conditions, the phospholipids arrange themselves in
sheets, the molecules aligning side by side in like orientation,
"heads" up and "tails" down. These sheets
then join tails-to-tails to form a bilayer membrane which
encloses some of the water in a phospholipid sphere. Typically,
several of these vesicles will form one inside the other in
diminishing size, creating a multilamellar structure of concentric
phosphlipid spheres separated by layers of water.
Utilizing ultra high-shear processing, the end result produces
liposomes which are of unilamellar structure, a single phospholipid
bilayer sphere enclosing water. Besides being much smaller
than multilamellar liposomes, these unilamellar liposomes
are of uniform size, usually 200 nanometers or less in diameter.
Additionally, the ultra high-shear mixing conditions allow
the phospholipids to align and orient themselves into bilayers
with more regularity than is possible with other processing
techniques, making them much more stable.
Liposomes have a long history in the study of biological
membranes. More recently, liposomes have been evaluated as
delivery systems for drugs, vitamins and cosmetic materials.
Liposomes can be custom designed for almost any need by varying
the lipid content, size, surface charge and method of preparation.
The preparation of liposomes requires careful attention to
ease of formulation, encapsulation efficiency and production
capacity.
Advantages of Liposomes
A special quality of liposomes is that they enable water soluble
and water insoluble materials to be used together in a formulation
without the use of surfactants or other emulsifiers. Water
soluble materials are dissolved in the water in which the
phospholipids are hydrated, and when the liposomes form these
materials are trapped in the aqueous center. The liposome
wall, being a phospholipid membrane, holds fat soluble materials
such as oils. Our proprietary ultra high-shear technology
refines this process, producing stable, unilamellar (single
layer) liposomes with specifically designed structural characteristics.
The resulting liposomes hold the normally immiscible materials
together in a microsphere with controllable release of the
encapsulated ingredients. The liposomes, and the otherwise
immiscible ingredients they contain, can then be used in formulations
without the need for surfactants or emulsifiers, eliminating
the drawbacks associated with the use of such.
The characteristics of liposomes also yield a variety of
other formulation benefits.
- Controlled Delivery System
- Biodegradable, Non-Toxic
- Carry Both Water and Oil Soluble Payloads
- Can Solubilize Recalcitrant Compounds
- Prevention of Oxidation
- Protein Stabilization
- Controlled Hydration
Release Kinetics of Liposomal
Payload
Liposomes are most useful for being able to transfer and deliver
active ingredients to the application site of cosmetics. The
liposome wall is very similar, physiologically, to the material
of cell membranes. When a cosmetic containing liposomes is
applied to the skin, for example, the liposomes are deposited
on the skin and begin to merge with the cellular membranes.
In the process, the liposomes release their payload of active
materials into the cells. As a consequence, not only is delivery
of the actives very specific--directly into the intended cells--but
the delivery takes place over a longer period of time. Cosmetic
ingredients in liposomes exhibit better stability, penetration
and efficacy at lower usage levels.
Liposomes as a delivery system can be made to release their
payload under a variety of conditions.
- Slow / Fast Release of Hydrophilic Payload
- Slow / Fast Release of Hydrophobic Payload
- Bilayer Composition
- Chain Length
- Saturation
- Lipid Class
- Physical Configuration of Liposome
- Solvent-Dependent Release
- pH-Dependent Release
- Temperature-Dependent Release
Types of Liposomes
Conventional Liposomes
- Stabilized Natural Lecithin (PC) Mixtures
- Synthetic Identical-Chain Phospholipids
- Glycolipid Containing Liposomes
Specialty Liposomes
- Bipolar Fatty Acids
- Antibody Directed
- Methyl / Methylene X-Linked
- Lipoprotein Coated
- Carbohydrate Coated
- Multiple Encapsulated
- Emulsion Compatible
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