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Topical products have been used for
centuries for treating local skin disorders, but using transdermal delivery systems
(TDS) for systemic delivery of drugs, hormones, and even nutritional factors is relatively new and gaining
rapidly in popularity.
For example, look at widespread use of estrogen and testosterone
patches. The administration of the steroid hormone precursors ptegnenolone
(PREG) and DHEA, as well as the natural hormone progesterone, via the transdermal route has
some important advantages over the oral delivery of these substances via standard capsules
and pills.
Three primary factors must be considered in developing
an effective system for transporting PREG, DHEA, and progesterone across the
skin and into the general circulation:
* The physiological,
biochemical and biophysical properties of skin
* The physicochemical
properties of the hormones and the delivery system
* The interactions
between skin and the delivery system
Because the skin is the largest metabolizing organ
in the body - even larger than the liver - it’s important to realize that the skin is capable
of metabolizing certain agents administered transdermally into inactive or potentially
harmful metabolites. Even if you overcome this factor, you have to make sure that the agent has the capacity to permeate the skin. Plus, you need
to know that the skin has the capacity to bind the agent to a point of saturation before
distribution of the agent via the bloodstream can commence.
The effective transdermal application of
PREG, DHEA, and
progesterone hormones is possible because these prerequisites are all met:
* These steroidal
hormones are small, fat-soluble molecules that are easily absorbed across
the skin where they can be stored in the fat tissues.
* The hormones
can reach a saturation level that is sufficiently high so that the fatty
tissue diffuses them into the capillaries for uptake by the general blood
circulation and transports them to
the target tissues.
* During the
transdermal delivery process, the skin does not inactivate these steroid
hormones, nor does it produce harmful metabolites from them.
An excellent composition for transporting PREG, DHEA,
and progesterone through the skin is an oil/water emulsion
that contains components of the fatty tissue of the skin
along
with suitable permeation enhancers. The fatty tissue
skin
components include vitamin A, vitamin E, and cholesterol.
Permeation enhancers are substances that
are especially compatible with steroid hormones,
because they enhance the skin’s permeation of
these hormones when they are administered at
the same time. (Remember: the skin forms a
protective barrier that must be penetrated.)
Effective permeation enhancers include alcohol
(such as ethanol and isopropanol), polyethylene
glycols, fatty acid molecules with 10 to 20
carbon rings and certain, mono-, di-, or
triglycerides of fatty acids.
Other possible ways of enhancing
transdermal delivery include the use of liposomes
and nanospheres. Liposomes are hollow spheres
made from phospholipids (such as lecithin) that
are up to 300 times smaller than skin cells. These
liposomes are filled with agents (in our case
PREC, DHEA, and/or progesterone) which
gradually into the skin and gradually release.
Nanospheres are even smaller micro-reservoir
particles. These porous polymers have a
special structure permitting very high absorption
and timed release of the agents into the skin.
Because liposomes and nanospheres are timed
release media, one must consider the rate of
release and lag time of the agent for reaching skin
saturation in order to diffuse into the capillaries
and enter the blood stream.
A proper TDS for administering
PREG, DHEA, and
progesterone: can provide close to the same level of
delivery of these steroid hormones as intravenous (IV) injection. IV injection
is considered to be the perfect delivery system for this
type of agent, but unfortunately, it requires medical supervision for best
results.
By comparison, transdermally delivered steroidal precursors
and hormones are up to 80%’ more bioavailable than equivalent
dosages of orally administered steroid hormones. This has been proven
by salivary hormone testing. In other words, oral delivery systems
provide only a fraction of biological activity in comparison to the
same dosage of steroid hormones administered from a TDS.
In practical terms, an oral dose of 25 mg DHEA might
be equivalent to 5 mg transdermally. The significance of
this is mostly economic - you don’t need to use as much of the hormone
when you use the transdermal form. Some people, less concerned
about the cost and more concerned about convenience, may still choose
to take the oral forms.
Oral delivery systems of PREG, DHEA, and progesterone,
in general, are less efficient for several reasons:
Individuals may have difficulties in absorbing these fat
soluble substances.
Improperly formulated pills using the wrong binder agents
and apsules using the wrong flow agents could impede the absorption of
the steroids from the gut. After a hormone is absorbed from the gut, it
is transported via the portal vein directly to the liver where much of
it is metabolized and conjugated for excretion in the bile. This is called-first
puss loss (or first-pass metabolism) through the liver.
If you add together the ingredient losses in each of the
above-mentioned steps, you come to the conclusion that
oral delivery
is less cost effective than a TDS for administering PREC, DHEA, and progesterone. It should be added, however, that oral
delivery of DHEA and PREG is more convenient for many people, especially given
that morning usage is preferred. [With this Issue of Life
enhancement, we are introducing a transdermal DHEA and PREG cream called DP-Transdermal
Reference:
1. Labrie C; Flamand M, Belangcr A, Labric F. High bioavailability
of dehydroepiandrosterone administered percutaneously in the rat. J Endocrin 1996;
150 (Suppl): S107 - S118. ISSUE 31 LIFE enhancement MARCH 1997
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