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SKIN STRUCTURE AND
BARRIER
PRESENTED BY
JITU HALDER, 1ST YEAR, M.PHARM
GUIDED BY DR.GOUTAM RATH
DEPARTMENT OF PHARMACEUTICS
ISF COLLEGE OF PHARMACY
CONTENTS
 INTRODUCTION
 STRUCTURE OF SKIN
 LAYERS OF SKIN
 FUNCTION OF SKIN
 SKIN BARRIERS
 DRUG TRANSPORT ACROSS THE SKIN
 FUNDAMENTALS OF SKIN PERMEATION
 CRITERIA FOR BEST CANDIDATE DRUG
 REFERENCES
2
INTRODUCTION
The skin is part of the integumentary system that covers the body.
It is the largest organ by mass and size.
Weight 4 kg and area 2 square meters.
It consists of four different types of tissue-
Connective tissue
Epithelial tissue
Muscle tissue
Nervous tissue
3
STRUCTURE OF SKIN
4
LAYERS OF SKIN
 Epidermis
 Dermis
 Hypodermis(subcutaneous)
 EPIDERMIS
• Outermost layer (also called cuticle)
• No blood vessels
• Small nerve endings
 5 layers
 Stratum corneum
 Stratum lucidum
 Stratum granulosum
 Stratum spinosum
 Stratum basale
Thickmess fro less than 0.1mm to nearly 1mm
5
LAYERS OF EPIDERMIS
6
CELLS IN THE EPIDERMIS
 KERATINOCYTES 85%,
 MELANOCYTES
 LANGERHANS CELLS
 MERKEL CELLS
7
DERMIS
 lies between the epidermis and the subcutaneous fat.
 It supports the epidermis structurally and nutritionally.
 Its thickness varies, being greatest in the palms and soles and
least in the eyelids and penis.
LAYERS OF THE DERMIS
 Papillary layers
consists of connective tissue
 Reticular layers
contain dense connective tissue, contain blood vessels, root of
hair folicle, oil gland, sweat gland, receptors
8
FIBRES OF THE DERMIS
When the skin is stretched, collagen, with its high tensile
strength, prevents tearing, and the elastic fibres,
intermingled with the collagen, later return it to the
unstretched state
1. Collagen makes up 70–80% of the dry weight of the
dermis.
2. Reticulin fibres are fine collagen fibres, seen in foetal
skin and around the blood vessels and appendages of
adult skin.
3. Elastic fibres account for about 2% of the dry weight of
adult dermis. 9
MUSCLES
 Both smooth and striated muscle are found in the
skin.
 The smooth arrector pili muscles are vestigial in
humans ,may help to express sebum.
 Responsible for ‘goose pimples’ (bumps) from cold,
nipple erection, and the raising of the scrotum by
the dartos muscle.
 Striated fibres (e.g. the platysma) and some of the
muscles of facial expression are also found in the
dermis.
10
HYPODERMIS(SUBCUTANEOUS)
 Fatty layer also called adipose
 Bottom most layer of the skin
 Varies in the thickness
 Gives smoothness and contour to te body
 Energy source
 Protective cushion for the outer skin
 Contain macrophages
11
FUNCTIONS OF THE SKIN
FUNCTION
 PROTECTION AGAINST:
Chemical, particles
Ultraviolet radiation
Antigen, haptens
Microbes
 Preservation of a balanced internal
env.
 Shock absorber
 Strong, yet elastic and compliant
 Temp. regulation
 Insulation
 Sensation
 Lubrication
 Protection
 Calorie reserve
 Vitamin D synthesis
 Body odour
STRUCTURE/CELL INVOLVED
 Horny layer
 Melanocyte
 Langerhans cells
 Langerhance cells
 Horny layer
 Horny layers
 Dermis and subcutaneous fat
 Blood vessels
 Eccrine sweat glands
 Subcutaneous fat
 Specialized nerve endings
 Sebaceous glands
 Nails
 Subcutaneous fat
 Keratinocytes
 Apocrine sweat glands
12
SKIN BARRIER
 According to the definition, barrier refers to an object that separates
two distinct spaces and/or prevents the free passage between two
environments. In this sense, the skin barrier ensures the integrity of
the body and controls the exchange of substances with the
environment.
SKIN AS A BARRIERS TO DRUG TRANSPORT
 Stratum corneum
 High density of skin
 Low hydration of skin
 Low area for solute transport ( Because most solute enter through
the 0.1 micron intercellular space.)
13
14
 Currently, it is considered that over 90% of the skin barrier function
resides in the epidermis and particularly in its outermost corneous
layer (stratum corneum)
 Initially, stratum corneum (SC) was considered an inert layer of dead
cells formed in the keratopoesis, interconnected through intercellular
lipid layer.
 SC with its main constituents the corneocytes and the intercellular
lamellar lipid bilayers, are considered the main structures
determining the speed of the transcutaneous exchange of substances.
 The mechanical resistance of the epidermal barrier is mainly due to
the corneocytes embedded in the so-called cornified envelope
 The main biochemical components of the skin barrier are lipids and
proteins
15
TRANSPORT ACROSS SKIN
16
PATHWAYS OF DRUG ABSORPTION
THROUGH THE SKIN
a) Transfollicular route
Transfollicular route is the shortest pathway that drug has to
follow to reach the systemic circulation that provides a
large area for diffusion of drugs .
b) Transcellular route
Drug delivering through this route passes from
corneocytes which has highly hydrated keratin creating
hydrophilic pathway. The drug passes through the
corneocytes of stratum corneum.
c) Intercellular route
In intercellular pathway the drug diffuses through the
continuous lipid matrix present between the cells.
17
FUNDAMENTALS OF SKIN PERMEATION
Rate of permeation, dQ/dt, across a skin can be expressed
as
dQ/dt = Ps [ cd – cr ]
Where
dQ/dt – Rate of permeation
Ps – permeability coefficient
Cd – Concentration in donor compartment
Cr – Concentration in receptor compartment
18
CRITERIA FOR BEST CANDIDATE DRUG
 molecular weight < 500 Da,
 melting point < 200 °C,
 log P octanol/water between 1 and 4,
 A dose < 50 mg per day, and ideally < 10 mg per day,
 ≤ 2 hydrogen-bonding groups,
 Not an irritant to the skin,
 Does not stimulate an immune reaction in the skin.
19
REFERENCES
 Darlenski R, et al, Skin Barrier Function : Morphological
Basis and regulatory mechanisms, Journal of clinical
medicine, 2011,(4),36-37
 Balazs Boglarka, Investigation of the skin barrier function
and transdermal drug delivery technique, University of
szeged, szeged ,2016
 Skin structure and function, https://en.wikipedia.org
(Accessed on October 23, 2018)
20

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Skin structure and Barriers

  • 1. SKIN STRUCTURE AND BARRIER PRESENTED BY JITU HALDER, 1ST YEAR, M.PHARM GUIDED BY DR.GOUTAM RATH DEPARTMENT OF PHARMACEUTICS ISF COLLEGE OF PHARMACY
  • 2. CONTENTS  INTRODUCTION  STRUCTURE OF SKIN  LAYERS OF SKIN  FUNCTION OF SKIN  SKIN BARRIERS  DRUG TRANSPORT ACROSS THE SKIN  FUNDAMENTALS OF SKIN PERMEATION  CRITERIA FOR BEST CANDIDATE DRUG  REFERENCES 2
  • 3. INTRODUCTION The skin is part of the integumentary system that covers the body. It is the largest organ by mass and size. Weight 4 kg and area 2 square meters. It consists of four different types of tissue- Connective tissue Epithelial tissue Muscle tissue Nervous tissue 3
  • 5. LAYERS OF SKIN  Epidermis  Dermis  Hypodermis(subcutaneous)  EPIDERMIS • Outermost layer (also called cuticle) • No blood vessels • Small nerve endings  5 layers  Stratum corneum  Stratum lucidum  Stratum granulosum  Stratum spinosum  Stratum basale Thickmess fro less than 0.1mm to nearly 1mm 5
  • 7. CELLS IN THE EPIDERMIS  KERATINOCYTES 85%,  MELANOCYTES  LANGERHANS CELLS  MERKEL CELLS 7
  • 8. DERMIS  lies between the epidermis and the subcutaneous fat.  It supports the epidermis structurally and nutritionally.  Its thickness varies, being greatest in the palms and soles and least in the eyelids and penis. LAYERS OF THE DERMIS  Papillary layers consists of connective tissue  Reticular layers contain dense connective tissue, contain blood vessels, root of hair folicle, oil gland, sweat gland, receptors 8
  • 9. FIBRES OF THE DERMIS When the skin is stretched, collagen, with its high tensile strength, prevents tearing, and the elastic fibres, intermingled with the collagen, later return it to the unstretched state 1. Collagen makes up 70–80% of the dry weight of the dermis. 2. Reticulin fibres are fine collagen fibres, seen in foetal skin and around the blood vessels and appendages of adult skin. 3. Elastic fibres account for about 2% of the dry weight of adult dermis. 9
  • 10. MUSCLES  Both smooth and striated muscle are found in the skin.  The smooth arrector pili muscles are vestigial in humans ,may help to express sebum.  Responsible for ‘goose pimples’ (bumps) from cold, nipple erection, and the raising of the scrotum by the dartos muscle.  Striated fibres (e.g. the platysma) and some of the muscles of facial expression are also found in the dermis. 10
  • 11. HYPODERMIS(SUBCUTANEOUS)  Fatty layer also called adipose  Bottom most layer of the skin  Varies in the thickness  Gives smoothness and contour to te body  Energy source  Protective cushion for the outer skin  Contain macrophages 11
  • 12. FUNCTIONS OF THE SKIN FUNCTION  PROTECTION AGAINST: Chemical, particles Ultraviolet radiation Antigen, haptens Microbes  Preservation of a balanced internal env.  Shock absorber  Strong, yet elastic and compliant  Temp. regulation  Insulation  Sensation  Lubrication  Protection  Calorie reserve  Vitamin D synthesis  Body odour STRUCTURE/CELL INVOLVED  Horny layer  Melanocyte  Langerhans cells  Langerhance cells  Horny layer  Horny layers  Dermis and subcutaneous fat  Blood vessels  Eccrine sweat glands  Subcutaneous fat  Specialized nerve endings  Sebaceous glands  Nails  Subcutaneous fat  Keratinocytes  Apocrine sweat glands 12
  • 13. SKIN BARRIER  According to the definition, barrier refers to an object that separates two distinct spaces and/or prevents the free passage between two environments. In this sense, the skin barrier ensures the integrity of the body and controls the exchange of substances with the environment. SKIN AS A BARRIERS TO DRUG TRANSPORT  Stratum corneum  High density of skin  Low hydration of skin  Low area for solute transport ( Because most solute enter through the 0.1 micron intercellular space.) 13
  • 14. 14
  • 15.  Currently, it is considered that over 90% of the skin barrier function resides in the epidermis and particularly in its outermost corneous layer (stratum corneum)  Initially, stratum corneum (SC) was considered an inert layer of dead cells formed in the keratopoesis, interconnected through intercellular lipid layer.  SC with its main constituents the corneocytes and the intercellular lamellar lipid bilayers, are considered the main structures determining the speed of the transcutaneous exchange of substances.  The mechanical resistance of the epidermal barrier is mainly due to the corneocytes embedded in the so-called cornified envelope  The main biochemical components of the skin barrier are lipids and proteins 15
  • 17. PATHWAYS OF DRUG ABSORPTION THROUGH THE SKIN a) Transfollicular route Transfollicular route is the shortest pathway that drug has to follow to reach the systemic circulation that provides a large area for diffusion of drugs . b) Transcellular route Drug delivering through this route passes from corneocytes which has highly hydrated keratin creating hydrophilic pathway. The drug passes through the corneocytes of stratum corneum. c) Intercellular route In intercellular pathway the drug diffuses through the continuous lipid matrix present between the cells. 17
  • 18. FUNDAMENTALS OF SKIN PERMEATION Rate of permeation, dQ/dt, across a skin can be expressed as dQ/dt = Ps [ cd – cr ] Where dQ/dt – Rate of permeation Ps – permeability coefficient Cd – Concentration in donor compartment Cr – Concentration in receptor compartment 18
  • 19. CRITERIA FOR BEST CANDIDATE DRUG  molecular weight < 500 Da,  melting point < 200 °C,  log P octanol/water between 1 and 4,  A dose < 50 mg per day, and ideally < 10 mg per day,  ≤ 2 hydrogen-bonding groups,  Not an irritant to the skin,  Does not stimulate an immune reaction in the skin. 19
  • 20. REFERENCES  Darlenski R, et al, Skin Barrier Function : Morphological Basis and regulatory mechanisms, Journal of clinical medicine, 2011,(4),36-37  Balazs Boglarka, Investigation of the skin barrier function and transdermal drug delivery technique, University of szeged, szeged ,2016  Skin structure and function, https://en.wikipedia.org (Accessed on October 23, 2018) 20