This is U.S. Army Major Jean M. Muderhwa’s microemulsion vaccine carrier. Credit: Courtesy of U.S. Army Major Jean M. Muderhwa |
A
researcher at the Brooke Army Medical Center (BAMC)/San Antonio
Military Medical Center (SAMMC) will present findings this week on a new
potential vaccine carrier that he hopes will extend the shelf life of
and aid in the stockpiling of critical vaccines.
U.S.
Army Maj. Jean M. Muderhwa recently presented at the Experimental
Biology 2012 meeting on a microemulsion he developed and that has been
found to be both stable and a good candidate for delivering a variety of
antigens. His findings will be presented at the American Society for
Biochemistry and Molecular Biology’s annual meeting, which is part of
EB2012.
“There
is a synergy here,” Muderhwa said of the microemulsion. “What I found
is a composition that is transparent, is liquid and that has been
sitting there (on my shelf) for six months” without degrading.
Muderhwa,
deputy laboratory director at the Medical Center’s Clinical
Investigation Department, made the microemulsion with what seems like a
simple recipe with five components, but it’s how those five components
interact that is quite special. He is hopeful that forthcoming animal
studies will show the full potential for the recipe.
“There
is a need (for new vaccine carriers like this) especially if we want to
stockpile a vaccine,” he emphasized. “The (U.S. Agency for
International Development) and FDA are responsible for stocking, for
example, the influenza vaccine in the case of epidemic. They have to
deliver them as quickly as possible. So if you have a vaccine just
sitting on the shelf for more than 10 or 20 years, you don’t have to
worry about its stability.”
The
first two parts of Muderhwa’s concotion, oil and water, are the basis
for just about any emulsion, many of which reside in most people’s
bathroom cabinets in the forms of creams and lotions. The third
component, glycerol, is also used in a variety of skin-care products.
The fourth component is a mixture of two high-molecular-weight,
pharmaceutically acceptable surfactants (Span 80 and Tween 60). The
fifth component, meanwhile, is an aluminum adjuvant-adsorbed protein
used in vaccines to amplify the immune system’s protective response to
whatever antigen is being delivered.
Compared
with the particles found in emulsions commonly used in creams and other
substances applied topically, the particles in microemulsions are
extremely tiny. And it’s precisely this property that Muderhwa has
harnessed and thinks deserves further study.
“If
I were to make an emulsion (of oil and water), which is just a cream
and white, that emulsion would separate within weeks,” he said. “If you
make a vaccine containing an emulsion, it’s only (good for) probably a
few months because the emulsion is not thermodynamically stable. The
surface tension is too high, and the molecules are repelling one another
until the emulsion fails.” An everyday example of this would be the
separation of salad dressing left in a refrigerator or pantry for a
couple of days. But when vaccines separate, giving them a good shake
doesn’t do the trick, making the administration of them more difficult.
“You
can make those particles in a cream smaller and smaller and smaller,”
he explained. “The way you do that is you have to lower the surface
tension to near zero. You know if you take water and put it in the oil,
they don’t mix. So you have to add a compound that can bring them
together. If you take egg yolk—it has phospholipids, and these are
emulsifiers—that helps to bring the water and oil to combine.”
Muderhwa
used a series of emulsifiers, such as Span 80 and Tween 60, and
glycerol as the co-emulsifier needed to lower the surface tension of the
tiny water and oil particles. That was only the first hurdle to
overcome. The real worry was how the then-four-part compound would react
if he added a fifth, the adjuvant needed to amplify the immune system’s
response to an antigen.
“Microemulsions
are very sensitive to change. If you add an extra compound, they (also)
separate quickly,” he said. “But what I discovered is that, if I take …
an aluminum adjuvant, which is the only one approved by the (Food and
Drug Administration) to be used in humans, and I mix that microemulsion
with the aluminum compound, … it is still stable.”
The aluminum adjuvant Muderhwa used is found in the influenza vaccine.
While
microemulsions are now used for drug delivery, such as antibiotics and
syrups, using them for vaccines could open up a new area of study, Maj.
Muderhwa said. These microemulsions are formed readily and sometimes
spontaneously, he said.
“Another
part of the presentation is for the future—to tell people that these
products can be used as a tool to investigate the effect of the surface
area on the immune response,” he explained. “If you make the molecules
smaller and smaller and smaller, what happens? What happens if you
increase the surface area? It will be interesting for research purposes
to see the effects when the surface area increases on the immune
response using this compound.”
Source: American Society for Biochemistry and Molecular Biology
Filed Under: Drug Discovery