Barbara, Calif. – March 14, 2005 – In a paper published
in the Proceedings of the National Academy of Sciences
(http://www.pnas.org/), a group of researchers led
by Samir Mitragotri, a professor of chemical engineering
at the University of California, Santa Barbara, reports
the identification of fundamental mechanisms that
may facilitate the design of safer and more efficacious
topical drug delivery systems.
Certain molecules, called chemical penetration enhancers
(CPEs) help drugs absorb through the skin. After analyzing
more than 100 different CPEs to better understand
how they manage to increase skin permeability, the
researchers engineered more than 300 new CPEs. The
design of the new CPEs was based on the researchers'
understanding of the molecular forces that are associated
with CPE safety and potency. They then screened the
new CPEs, first using computer technology and then
testing the most promising ones in the laboratory
environment. The molecules identified broaden the
number of CPEs that can be used in the design of transdermal,
cosmetic and pharmaceutical products.
"The methods used in this
research not only increase our ability to create effective
new CPEs, but they also will expand our ability to
evaluate potential new CPEs for safety and efficacy,"
said Mitragotri. "By enhancing our ability to
deliver drugs topically, we will be able to reduce
the number of drugs that must be given by injection."
The skin is composed of several
layers. The top layer, Stratum Corneum (SC) is made
of dead cells that contain proteins and lipid molecules
which are arranged in bi-layers. The SC is a significant
barrier to the absorption of drug molecules across
the skin. CPEs help drug molecules penetrate into
the skin by changing the structure of the SC.
Different CPEs penetrate the
skin in unique ways. For example, some make microscopic
holes in the SC by removing lipids. Others insert
themselves in already-crowded lipid bi-layers to disorganize
them. Some can also break open the dead cells in the
SC and interact with the protein in those cells. CPEs
that cause skin irritation are typically associated
with the unfolding of proteins in skin cells.
By studying the molecular properties
of a CPE, its propensity to penetrate or irritate
the skin can be predicted. Simply put, the researchers
draw a CPE's structure on a computer, input its molecular
properties, and then compute its penetrability or
effectiveness and its potential to irritate the skin.
Such computer-aided modeling
facilitates the analysis of millions of molecules,
allowing researchers to then submit the most promising
candidates to further in-vivo laboratory analysis.
Barbara Bronson Gray: 818.889.5415;