3 Barrier Surfaces of Skin M. M. MERSHON
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Biomedical Laboratory, Edgewood Arsenal, Aberdeen Proving Ground, Maryland 21010 Stratum corneum, the nonliving layer of skin, is refractory as a substrate for chemical reactions, but it has a strong physical affinity for water. The chemical stability of stratum corneum is evident in its mechanical barriers which include insoluble cell membranes, matrix-embedded fibers, special ized junctions between cells, and intercellular cement. The hygroscopic properties of stratum corneum appear to reside in an 80 Α-thick mixture of surface-active proteins and lipids that forms concentric hydrophilic interfaces about each fiber. This combination of structural features and surface -activeproperties can explain how stratum corneum retains body fluids and prevents disruption of living cells by envi ronmental water or chemicals. ' " " p h e s t r a t u m c o r n e u m , the outermost l a y e r of s k i n , controls w a t e r flux A
a n d t h e r e b y protects o u r tissues f r o m f a t a l d r y i n g a n d f r o m o s m o t i c
damage b y bathing. This tough,
flexible
l a y e r restricts the passage of
m o s t substances to a d e g r e e t h a t varies w i t h the substance a n d t h e c o n ditions of exposure. P e r m e a t i o n is l i m i t e d b y i n t e r r e l a t e d c o n t r i b u t i o n s of s t r u c t u r a l elements, t i m e factors, s p a t i a l arrangements, c h e m i c a l c o m p o sitions, a n d p h y s i c a l p r o p e r t i e s . Differences Among
Barriers
Size. S t r a t u m c o r n e u m surfaces t h a t i m p e d e d i f f u s i o n f a l l i n t o f o u r sizes. T h e largest structures, s u c h as h a i r a n d the c o r n i f i e d surface, are v i s i b l e . C e l l surfaces, t h e i r interfaces, a n d t h e i r elaborations are m i c r o scopic.
K e r a t i n i z e d elements are u l t r a m i c r o s c o p i c .
F i n a l l y , interactions
b e t w e e n solvents, solutes, a n d b a r r i e r surfaces o c c u r o n the m o l e c u l a r level.
T h e functions of these structures are i n t e g r a t e d i n t o a n o v e r a l l
barrier capability. 41 Baier; Applied Chemistry at Protein Interfaces Advances in Chemistry; American Chemical Society: Washington, DC, 1975.
42
APPLIED CHEMISTRY A T PROTEIN
INTERFACES
PERCUTANEOUS ABSORPTION OF SOLUTIONS WITH TIME AND SITE sweat duct
hair
stratum corneum solution str. corneun air bubble basal cells capillary
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dermis sweat duct hair shaft Figure 1. Schematic drawing showing relative sizes of sweat ducts, hair follicles, and cornified layers of human abdominal skin. Approximate transient concentrations of polar molecules in each site at different times are shown by variations in density of stippling. Adapted from Réf. 1. Routes of E n t r y .
M i c r o s c o p i c sections s h o w t h e s t r a t u m c o r n e u m
( S C ) of t h e a b d o m e n as t h i n layers of d e a d , flattened cells a r r a y e d over a m u c h t h i c k e r l a y e r of e p i t h e l i a l cells. B o t h layers are p i e r c e d at i n t e r vals b y h a i r f o l l i c l e s a n d sweat ducts ( F i g u r e 1 ) ( 1 ). S e b u m flows into, l u b r i c a t e s , a n d tends to fill t h e space b e t w e e n e a c h h a i r shaft a n d its s u r r o u n d i n g c o n i c a l sheath (2).
S w e a t ducts a r e c e l l u l a r tubes
that
s p i r a l t h r o u g h e p i d e r m i s w i t h i n c r e a s i n g r a d i u s a n d d e c r e a s i n g p i t c h (3). T h e r e f o r e , t h e y a p p r o a c h t h e surface at a n acute angle a n d e m p t y t h r o u g h s l i t - l i k e pores
(2,3).
C o n f l i c t i n g e v i d e n c e a n d d i v e r g e n t v i e w s exist c o n c e r n i n g t h e r e l a t i v e capacities of h a i r f o l l i c l e s , sweat ducts, a n d S C as p a r a l l e l routes f o r a d m i s s i o n o f c h e m i c a l s (1, 2, 4r-21).
P r e f e r e n t i a l p e n e t r a t i o n of f o l l i c l e s
a n d t h e i r associated sebaceous glands is suggested b y tracer studies u s i n g dyes, h e a v y metals, a n d s u l f o n a m i d e s (4).
T h i s i n d i c a t i o n is r e i n f o r c e d
b y results w i t h a p p l i c a t i o n s of h i s t a m i n e o r n a p h t h a z o l i n e base hydrocortisone
or organophosphorus
pesticides
( 6 ) , o r other
(5),
organo-
phosphates (7). T h e s e d r u g s p r o d u c e e n h a n c e d responses i n areas w h e r e sebaceous glands a r e m o s t n u m e r o u s . H o w e v e r , responses to e t h y l n i c o tinate ( 5 ) a n d r a d i o a c t i v e tracer studies w i t h t r i b u t y l p h o s p h a t e s h o w n o difference
between
h a i r y a n d h a i r - f r e e areas.
M a i b a c h a n d associates suspect that differences
(8)
Furthermore,
i n S C , rather than i n
f o l l i c u l a r p e n e t r a t i o n , a c c o u n t f o r i n c r e a s e d a b s o r p t i o n i n h a i r y sites (6). F r e d r i k s s o n (9) suggests that c h e m i c a l affinities c a n e x p l a i n t h e h i g h concentrations of l a b e l e d pesticides t h a t h e f o u n d i n ducts a n d f o l l i c l e s (10).
Baier; Applied Chemistry at Protein Interfaces Advances in Chemistry; American Chemical Society: Washington, DC, 1975.
3.
MERSHON
Barrier
43
Surfaces of Skin
T h e a v a i l a b l e d a t a a r e s i m i l a r l y d i v e r g e n t f o r p e n e t r a t i o n via sweat ducts. V a n K o o t e n a n d M a l i (11) estimate t h a t sweat ducts c o n t a i n 7 0 % of t h e p r e c i p i t a t e f o r m e d w h e n p o t a s s i u m f e r r o c y a n i d e a n d a m m o n i u m ferrisulfate diffuse i n t o s k i n f r o m opposite suggests
preferential sweat-duct
pounds.
Wahlberg
(13)
sides
conduction
T h i s result
(10, 12).
of strongly ionized
c a m e to t h e opposite
conclusion,
com
i.e., t h a t
s o d i u m c h l o r i d e passes t h r o u g h S C faster t h a n i t does t h r o u g h ducts o r follicles (6, 12).
S u c h strongly ionized or polar compounds
penetrate s k i n v e r y p o o r l y
generally
(4,14,15,16).
S c h e u p l e i n a n d associates r e p o r t that p o l a r steroids p e n e t r a t e p r e f e r e n t i a l l y t h r o u g h sweat ducts a n d h a i r follicles w h i l e m o r e l i p i d - s o l u b l e steroids a n d p r i m a r y alcohols penetrate r a p i d l y i n S C (16, 17). Downloaded by UNIV LAVAL on June 8, 2017 | http://pubs.acs.org Publication Date: June 1, 1975 | doi: 10.1021/ba-1975-0145.ch003
tant p r o p e r t i e s of c o m p o u n d s
Surfac
f a c i l i t a t e t h e i r p e n e t r a t i o n of ducts a n d
follicles (18). H o w e v e r , massage displaces a i r a n d i m p r o v e s p e n e t r a t i o n t h r o u g h f o l l i c u l a r structures (19).
L i n d s e y (14) reconciles s u c h d i v e r s e
e v i d e n c e b y stating t h a t b a r r i e r p r o p e r t i e s d o n o t d e p e n d o n structures, b u t t h e y v a r y w i t h t h e p r o p e r t i e s o f the p e n e t r a n t . H a i r shafts also constitute routes of e n t r y ; w a t e r a n d o t h e r c h e m i c a l s t e n d to diffuse t h r o u g h h a i r shafts m o r e r e a d i l y t h a n t h r o u g h S C (20). S o m e o r g a n i c solvents enter s k i n t h r o u g h u n p r o t e c t e d h a i r t h a t p r o t r u d e s t h r o u g h a n i m p e r v i o u s c o a t i n g over S C , pores, a n d f o l l i c u l a r openings (22). Biphasic Diffusion.
M u c h of t h e c o n f u s i o n
has b e e n r e s o l v e d b y S c h e u p l e i n (1).
a b o u t routes of e n t r y
H i s w o r k shows t h a t a n y o n e of
the routes c a n b e d o m i n a n t u n d e r a p p r o p r i a t e c o n d i t i o n s .
F o r instance,
d o m i n a n c e m a y v a r y w i t h t i m e ( F i g u r e 2 ). S c h e u p l e i n o b s e r v e d b i p h a s i c diffusion w i t h r a p i d onset a n d i n i t i a l d o m i n a n c e of flux via ducts, h a i r , 3h -J
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2
Rapid diffusion occurs through hair and sweat ducts during time lag for stratum corneum.
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