Skin structure and Barriers

A brief description of human skin structures and barriers. Its include elaborate description of skin structure and basics of skin barriers which prevent or control the trans dermal drug delivery.

1. SKIN STRUCTURE AND BARRIER PRESENTED BY JITU HALDER, 1 ST 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

4. STRUCTURE OF SKIN 4

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

6. LAYERS OF EPIDERMIS 6

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

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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

16. TRANSPORT ACROSS SKIN 16

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