American Journal of Agricultural and Biological Sciences 3 (2): 444-450, 2008
ISSN 1557-4989
© 2008 Science Publications
Corresponding Author: Aroonsri Priprem, Faculty of Pharmaceutical Sciences, Khon Kaen University,
Khon Kaen 40002, Thailand Tel: +66-43-362092 Fax: +66-43-362092
444
Comparative Permeation Studies between Scale Region of Shed Snake Skin
and Human Skin In vitro
Aroonsri Priprem, Chidchanok Khamlert, Thaned Pongjanyakul,
Sarayut Radapong, Theera Rittirod and Padungkwan Chitropas
Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
Abstract: Scales of shed king cobra (Ophiophagus hannah) skin from the dorsal portions, (SSS) and
human breast epidermis (HE) were used as barrier membranes for comparison in an in vitro drug
permeation study of nine active compounds (MW range 150-300 g mol
-1
, pK
a
3-10). Each compound,
saturated in a donor solution at pH 4.0 or 5.6, permeated through the barrier membrane, fully hydrated.
A receptor solution at pH 7.4 was sampled for quantification at its λ
max
by UV-Visible
spectrophotometry and/or HPLC. The permeability coefficients of nine compounds were correlated to
the n-octanol/water partition coefficients of these compounds. The permeability coefficient of these
compounds using HE and SSS was correlated. Scales of shed skin from the dorsal portions of king
cobras were shown to be well correlated to the human breast epidermis in this in vitro aqueous
permeation study of these compounds.
Key words: Scale region, shed king cobra skin, human skin, permeation, barrier membrane
INTRODUCTION
Permeation of drugs through the skin barrier has
been the basis of transdermal delivery
[1]
. The human
skin is an effective and selective barrier to chemical
permeation
[2]
; however, it is not always possible to do
actual skin permeation studies in humans. In vitro
permeation studies and model barrier membranes using
excised skins (human cadaver and animals) or artificial
materials have been employed. Animal skins generally
gave higher permeation profiles than the human skin
because of the differences in thickness, stratum
corneum, density of hair follicles, sweat glands and
appendages
[3]
. The idea of using shed snake skin as the
barrier membrane in in vitro permeation studies was
introduced by Higuchi and Kans
[4]
. It is a non-living
tissue which can be obtained without sacrifices, lacks
hair follicles, and gives less variation than human or
animal skin. Shed skins of several snakes, such as
Elaphe obsoleta
[3,5,6,7,8]
, Python reticulatus
[9]
and
Ophiophagus hannah
[10]
, have been investigated.
Haigh et al.
[7]
emphasized the effect of species, sites
and regions of the shed snake skin used. Good
correlation of results to human skin suggested the use
of shed snake skin as a model membrane for
permeation studies despite the differences in anatomical
and chemical compositions
[5,11,12]
. Haigh et al.
[7]
suggested that the differences in lipid contents, a vital
component of the skin, between shed snake and human
skin could affect the permeability of compounds.
Shed snake skin usually consists of three
distinctive layers; beta, mesos and alpha-layers
[3]
.
Major lipid compositions of shed snake skins are
phospholipids while that of the human skin are
ceramides
[13]
. Shed snake skin is composed of two very
different regions; scales and separating these, hinges.
The scales are rigid while the hinge is elastic. The
scales on the dorsal part are much smaller and usually
thinner than the scales on the ventral part. Most of the
studies related to the use of shed snake skins employed
whole skin which included the scales and hinges,
except that of Harada et al.
[9]
which used only the
scales of Python reticulatus for in vitro permeability of
salicylic acid.
Factors affecting the permeation of different
compounds include ionization
[14]
, partition, and
molecular weight
[14]
. Takahashi et al.
[6]
used six basic
compounds with low pK
a
(0.6-5.3) and found that
non-ionized forms permeated at a greater rate
(0.01-33.3×10
-3
cm h
-1
). Potts and Guy
[15]
selected more
than 90 compounds from various reports with
molecular weights ranging from 18 to 750 and
n-octanol/water partition coefficients (log K
o/w
) ranging
from 3 to 6 to predict skin permeability using multiple
linear regressions.