Pathway for Skin Penetration.ppt

(1)

(2)

What is skin components

(3)

(4)

What is penetration ?

Skin penetration is differs from skin

Skin penetration is differs from skin

permeation.

skin penetration

skin penetration is the former describes _{is the former describes}

the passage of an ingredients into the

skin ( we hope to the target skin layer).

Skin permeation

Skin permeation is the passage of an _{is the passage of an}

ingredient through the skin to the

ingredient through the skin to the

circulatory system.

(5)

Interaction between a

given compound

and the skin is

physicochemical in

nature.

(6)

what is the penetration pathway?

(Penetration between SC corenocytes is

(Penetration between SC corenocytes is

the pathway by witch most compounds

penetrate the skin

penetrate the skin ) ) 1.

1. The intercellular pathway _{The intercellular pathway}.*(.*(5%-30%of 5%-30%of total area)

total area)

2.

2. The intracellular pathway The intracellular pathway

3. The intrafollicular pathway and the

3. The intrafollicular pathway and the

sebaceous glands pathway

4. The polar pathway .

(7)

The intercellular pathway

and the intracellular

pathway

* Hydrophilic compounds

* Hydrophilic compounds may_may preferably _preferably

partition into the intracellular domain

*lipophilic compound

*lipophilic compound may_may cross the SC _{cross the SC}

through the intercellular rout.

So the major pathway for a compound is

So the major pathway for a compound is

highly dependent upon its partition

coefficient.

(8)

stratum corneum constituents

75%-80% protein , 5%-15% lipids , 5%-10% unidentified element

(9)

Skin can

absorb water

and the proof and the proof

(10)

The intrafollicular pathway and the

sebaceous glands pathway

*(Mainly for lipid and surprisingly it is for

a charge and large polar molecule) .

sebaceous gland on the total skin surface

represent not more than 0.1% , but some

represent not more than 0.1% , but some

time it will be the target such as acne

(11)

Follicle distribution

(12)

The polar pathway

This route is believed to be

hydrophilic in natural , it is

composed of aqueous region

surrounded by polar lipids

that create the walls of

microchannels.

(13)

The polar pathway

The localization of the

hydrophilic pores is unclear,

but they think that :

1- it is intercellular .

2- it is intracellular keratin .

(14)

The polar pathway

We need 3-10 corneocytes to create a

columns that form a cluster.

Corneocytes edges inside each cluster

were found to intercalate extensively

, but neighboring cluster were

separated by gaps of a few

micrometers.

(15)

The polar pathway

So know we will say that we have

2 different hydrophilic pathway :

1- inter-cluster rout (within low

penetration resistant)

2- inter-coreocyte pathway (higher

penetration resistance), it is

twisted between coreocyte ,may

be act as an actual channel in

(16)

(17)

Factor Affecting Skin Penetration

1- size of the molecule and MW.

1- size of the molecule and MW.

2- affinity of the molecule to the surface of the skin.

3- compatibility with the intercellular lipids.

4- the skin condition.

5- the moisture content.

5- the moisture content.

6- tempreture .

7- thickness of the SC.

8- physical integrity.

(18)

size of the molecule.

*smaller size more penetration.

*molecular weight (MW) of a

compound must be under 500

Dalton to allow skin absorption.

(19)

the skin condition

Scarred skin in Comparison to

normal skin will be with no hair

follicle and sebaceouse gland and

thinning of the collagenouse

fibers , penetration rate throw

Scarred skin will be so less than

normal skin .

(20)

compatibility with the intercellular

lipids

To do that we use

Penetration

enhancers

witch is a substances that

can partition into, and interact with,

skin constituents .

(21)

thickness of the SC

By increasing the thickness of

the SC amount of water and

lipid will increase and

penetration of the skin

increase. (sink condition)

(22)

The moisture content

As the amount of free moisture in the

intercellular spaces increases the

intercellular become larger and the

amount of a substances penetrating

the skin increase .

(the mechanism by witch hydration

increase skin penetration is not will

understood)

(23)

tempreture

As the tempreture increases the

As the tempreture increases the

penetration increase , because of :

1- lowering of the activity coefficient of

pharmaceutical substances in the skin.

2- increases in drug solubility.

3- increase in diffusion and blood flow .

3- increase in diffusion and blood flow .

4- transition from gel to liquid crystal of

layer lipid hydrocarbon chain will

reduce the viscosity so increase the

duffusion.

(24)

Penetration Enhancer

There are more than one way to

There are more than one way to

differentiate and classify skin

penetration enhancer :

1

1- classifying them according to the _{- classifying them according to the}

preferred rout of penetration.

2- according to carry different molecule .

2- according to carry different molecule .

3

3- according to their mechanism of - according to their mechanism of enhancement.

(25)

Penetration Enhancer according to

the

preferred rout

of penetration

1- solvent that enhance penetration

through both polar and non-polar

pathway.

2- enhancers that preferentially affect

the polar route .

3- enhancer that mainly modify the

non-polar route.

(26)

the preferred rout of penetration

1- solvent that enhance penetration

through both polar and non-polar

pathway such as:

a.

2-pyrrolidone

b. N-methyl pyrrolidone

c.

N-methyl-formaide

d. propylene glycol in combination

with azon.

(27)

2- enhancer that mainly

modify the non-polar route,

such as :

a.

propylene glycol and oleic

acid.

b.

(28)

3- enhancers that preferentially

affect the polar route , such as:

a. Propylene glycol in combination

(29)

The 3 major mechanisms (polar) :

The 3 major mechanisms (polar) :

1.

1. Extraction the SC lipids: (The Extraction the SC lipids: (The permeability coefficient of polar

permeability coefficient of polar

molecule increased with increasing lipid

extraction).

2. Inducing a relaxation of the polymeric

structure of the cytoplasmic matrix in

structure of the cytoplasmic matrix in

keratinocytes cell.

3. Changing the solvent properties of the

SC. (surfactant)

(30)

Penetration Enhancer according to

*Surfactant:

enhance transport of polar molecule by

enhance transport of polar molecule by

solubilization and removal of

intercellular lipid and binding to keratin

filament of the intracellular matrix , this

resulted in cell order disruption .

resulted in cell order disruption .

non-ionic surfactant were shown to shows

fluidizing effect on the SC.

(31)

Penetration Enhancer according to

their

mechanism

of enhancement.

1- Enzyme .

2- Chemical enhancers .

3- Vesicular system .

4- Ceramides (one of the lipid classes

in the SC).

(32)

(1) Enzyme

Using an enzyme to affect the

barrier properties of the SC

refer to either affecting activity

of :

1- enzyme present in the skin.

2- Or to enzyme applied to it from

(33)

How dose the enzyme work ?

1- by affecting the synthesis of lipid class

1- by affecting the synthesis of lipid class

in SC (fatty acid, cholesterol and

ceramides), such as:

* 5-(tetradecyloxy)-2-furancarboxylic

acid. this will prevent fatty acid

synthesis.

* Fluvastatin .

(34)

How dose the enzyme work ?

2-by affecting metabolism and

2-by affecting metabolism and

biochemical cascade in the skin , such

as:

* papian ; is a proteolytic enzyme , that

increase the SC thickness , and the

living epiderm.

(35)

How dose the enzyme work ?

3- subtissues phase separation ,

lamellar bodies formation and

created disorder in lamellar

(36)

(2) Chemical enhancers

Most chemical enhancers affect the

intercellular lipid bilayers in the

SC , it allows the creation of various

types of (openings) in the bilayers.

Example:

* isopropyl myristate.

* isopropyl alcohol.

* oleic acid.

(37)

Chemical enhancers

*

oleic acid :

It was observed that oleic acid

make alteration in the SC

specifically in the intercellular

spaces.

(38)

Another Chemical

enhancers

(39)

Penetration enhancers (

DMSO)

*

*Dimethyl sulfoxide (DMSO):Dimethyl sulfoxide (DMSO):

By changing in the conformation of the skin

Keratins from an α-helical to a β-sheet

Conformation ,that happen because of (DMSO

tended to bind to free water before the

tended to bind to free water before the

protein-bound water was replaced and the

protein conformational changes were

induced.

(40)

Penetration enhancers (azon)

Azone may act on the lipid-rich route

Azone may act on the lipid-rich route

because it fluidizes the stratum corneum

lipids .

on the water-rich route because it

enriches the water content .

enriches the water content .

The reason why Azone affects the skin

permeation of a relatively broad

spectrum of drugs may be that it affects

at least two permeation routes in the

at least two permeation routes in the

skin barrier

(41)

(3) Vesicular system

What is Vesicular system ?

It is an Encapsulation of the

drug in vesicular structures

such as liposomes

(42)

A major force driving vesicle

penetration through the skin

may be the water gradient across

(43)

We have

We have

*

* classic multi-layered phosphoplipid _{classic multi-layered phosphoplipid}

liposomes

liposomes :_:

Act as a reservoir and would not be the

carrier of choice.

*

*SC lipid-based liposomesSC lipid-based liposomes::

were found to deliver a greater amount of

were found to deliver a greater amount of

the drug to the deep layer of the skin

(epidermis and dermis) , the larger the

mean size the poorer the penetration to

SC layer.

(44)

(3) Vesicular system

On the another hand the scientist found

On the another hand the scientist found

that :

*phospholipids liposomes increase SC

lipid bilayer disorder and increase

permeation

permeation ..

*SC lipid-based liposomes have a high

affinity to the SC and generate a

affinity to the SC and generate a

reservoir because it increase the order

of the lipid in the intercellular

lamellae

(45)

(46)

(4) ceramides

Ceramides in certain concentration were

Ceramides in certain concentration were

shown to create an imbalance in the

intercellular lamellar organization and

to enhance skin penetration .

In the study *they found that polar head

In the study *they found that polar head

of an enhancer is responsible for the

penetration , and they found *that

branched-chain alcohol have lower

enhancement capability than the

enhancement capability than the

primary alcohol.

(47)

It is recommended to choose

enhancers with different

mechanisms of action ,

this will prevent

competition at the site of

action and has a better

probability of not

provoking irritation

(48)

Summary

We talk a bout four of the skin penetration

We talk a bout four of the skin penetration

pathways (

pathways (the intercellular the intercellular

pathway ,the intracellular pathway, the

intrafollicular pathway and the

sebaceous glands pathway, and the polar

pathway

pathway) and four types of penetration ) and four types of penetration enhancer (

enhancer (enzymes, chemical _{enzymes, chemical}

enhancer , and the vesicular system ,

ceramides

(49)

(50)

References



 Cosmetic & toiletries magazine.(vol.120,No. 6/2005)Cosmetic & toiletries magazine.(vol.120,No. 6/2005)



 Delivery System Handbook for Personal Care and Cosmetic Delivery System Handbook for Personal Care and Cosmetic Products. By Meyer

Products. By Meyer



 Bos ,J.D., Meinardi ,M.M..(2000). The 500 Dalton rule for Bos ,J.D., Meinardi ,M.M..(2000). The 500 Dalton rule for the skin penetration of chemical compounds and drugs.

the skin penetration of chemical compounds and drugs.

experimental terminology. 9(3), 165-9.



 Harry s cosmeticology (eighth edition ) page 352 Harry s cosmeticology (eighth edition ) page 352



 Tanja ,M.Greve .Kristine ,B.Andersen ,Ole ,F.Nielsen2..Tanja ,M.Greve .Kristine ,B.Andersen ,Ole ,F.Nielsen2.. (2008). Penetration mechanism of dimethyl sulfoxide in

(2008). Penetration mechanism of dimethyl sulfoxide in

human and pig ear skin: An ATR–FTIR and near-FT

Raman spectroscopic in vivo and in vitro study. 22(9).

405-417.

417.



 Mechanism of skin penetration-enhancing effect by Mechanism of skin penetration-enhancing effect by laurocapram (the name of article)