Applied Chemistry at Protein Interfaces - ACS Publications - American

These show that some polar molecules travel 50 times as fast in hair and follicles and .... Cell removed from the abdominal skin of a man by washing w...
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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

Downloaded by UNIV LAVAL on June 8, 2017 | http://pubs.acs.org Publication Date: June 1, 1975 | doi: 10.1021/ba-1975-0145.ch003

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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< Λ ,« c/)

2

Rapid diffusion occurs through hair and sweat ducts during time lag for stratum corneum.

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