Invited
Speaker
Effect of Different Enhancers on The Transdermal Permeation
of Insluin Analog
Krishna M. Yerramsetty, Vijay K. Rachakonda, Brian J. Neely,
Sundararajan V. Madihally and Khaled A. M. Gasem
USA
Using chemical penetration enhancers (CPEs), transdermal drug delivery
(TDD) offers an alternative route for insulin administration, wherein
the CPEs reversibly reduce the barrier resistance of the skin. However,
there is a lack of sufficient information concerning the effect of
CPE chemical structure on insulin permeation. To address this limitation,
we examined the effect of CPE functional groups on the permeation
of insulin. A virtual design algorithm that incorporates quantitative
structure-property relationship (QSPR) models for predicting the CPE
properties was used to identify 43 potential CPEs. This set of CPEs
was prescreened using a resistance technique, and the 22 best CPEs
were selected. Next, standard permeation experiments in Franz cells
were performed to quantify insulin permeation.
Our results indicate that specific functional groups are not directly
responsible for enhanced insulin permeation. Rather, permeation enhancement
is produced by molecules that exhibit positive log Kow
values and possess at least one hydrogen donor or acceptor. Toluene
was the only exception among the 22 potential CPEs considered. In
addition, toxicity analyses of the 22 CPEs were performed. A total
of eight CPEs were both highly enhancing (with permeability coefficient
at least four times the control value) and non-toxic; of which, five
of these are new discoveries.
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