Pathway for skin penetration.ppt(1)

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  • *Delivery System Handbook for Personal Care and Cosmetic Products . By Meyer
  • *Delivery System Handbook for Personal Care and Cosmetic Products . By Meyer
  • Bos ,J.D., Meinardi ,M.M..(2000). The 500 Dalton rule for the skin penetration of chemical compounds and drugs. experimental terminology. 9(3), 165-9.
  • Harry s cosmeticology (eighth edition ) page 352
  • *
  • Tanja ,M.Greve .Kristine ,B.Andersen ,Ole ,F.Nielsen2..(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.
  • Mechanism of skin penetration-enhancing effect by laurocapram (the name of article)
  • Pathway for skin penetration.ppt(1)

    1. 1. GHAZWA SHAWASH بسم الله الرحمن الرحيم University Of Jordan
    2. 2. Pathway For Skin Penetration
    3. 3. What is skin components ?
    4. 5. What is penetration ? <ul><li>Skin penetration is differs from skin permeation. </li></ul><ul><li>skin penetration is the former describes the passage of an ingredients into the skin ( we hope to the target skin layer). </li></ul><ul><li>Skin permeation is the passage of an ingredient through the skin to the circulatory system. </li></ul>
    5. 6. <ul><li>Interaction between a given compound and the skin is physicochemical in nature. </li></ul>
    6. 7. what is the penetration pathway? <ul><li>(Penetration between SC corenocytes is the pathway by witch most compounds penetrate the skin ) </li></ul><ul><li>The intercellular pathway .*( 5%-30%of total area) </li></ul><ul><li>The intracellular pathway </li></ul><ul><li>3. The intrafollicular pathway and the </li></ul><ul><li>sebaceous glands pathway </li></ul><ul><li>4. The polar pathway . </li></ul>
    7. 8. The intercellular pathway and the intracellular pathway <ul><li>* Hydrophilic compounds may preferably partition into the intracellular domain </li></ul><ul><li>*lipophilic compound may cross the SC through the intercellular rout. </li></ul><ul><li>So the major pathway for a compound is highly dependent upon its partition coefficient. </li></ul>
    8. 9. stratum corneum constituents 75%-80% protein , 5%-15% lipids , 5%-10% unidentified element
    9. 10. <ul><li>Skin can </li></ul><ul><li>absorb water </li></ul><ul><li>and the proof </li></ul><ul><li>is wrinkle of this finger </li></ul>
    10. 11. The intrafollicular pathway and the sebaceous glands pathway <ul><li>*(Mainly for lipid and surprisingly it is for a charge and large polar molecule) . </li></ul><ul><li>sebaceous gland on the total skin surface represent not more than 0.1% , but some time it will be the target such as acne </li></ul><ul><li>*Delivery System Handbook for Personal Care and Cosmetic Products . By Meyer </li></ul>
    11. 12. Follicle distribution
    12. 13. The polar pathway <ul><li>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. </li></ul>
    13. 14. The polar pathway <ul><li>The localization of the </li></ul><ul><li>hydrophilic pores is unclear, </li></ul><ul><li>but they think that : </li></ul><ul><li>1- it is intercellular . </li></ul><ul><li>2- it is intracellular keratin . </li></ul>
    14. 15. The polar pathway <ul><li>We need 3-10 corneocytes to create a columns that form a cluster. </li></ul><ul><li>Corneocytes edges inside each cluster were found to intercalate extensively , but neighboring cluster were separated by gaps of a few micrometers. </li></ul>
    15. 16. The polar pathway <ul><li>So know we will say that we have 2 different hydrophilic pathway : </li></ul><ul><li>1- inter-cluster rout (within low penetration resistant) </li></ul><ul><li>2- inter-coreocyte pathway (higher penetration resistance), it is twisted between coreocyte ,may be act as an actual channel in the skin. </li></ul>
    16. 17. it is also thought to be the route by whitch water evaporates through the skin
    17. 18. Factor Affecting Skin Penetration <ul><li>1- size of the molecule and MW. </li></ul><ul><li>2- affinity of the molecule to the surface of the skin. </li></ul><ul><li>3- compatibility with the intercellular lipids. </li></ul><ul><li>4- the skin condition. </li></ul><ul><li>5- the moisture content. </li></ul><ul><li>6- tempreture . </li></ul><ul><li>7- thickness of the SC. </li></ul><ul><li>8- physical integrity. </li></ul>
    18. 19. size of the molecule. <ul><li>*smaller size more penetration. </li></ul><ul><li>*molecular weight (MW) of a </li></ul><ul><li>compound must be under 500 </li></ul><ul><li>Dalton to allow skin absorption. </li></ul><ul><li>*Bos ,J.D., Meinardi ,M.M..(2000). The 500 Dalton rule for the skin penetration of chemical </li></ul><ul><li>compounds and drugs. experimental terminology. 9(3), 165-9. </li></ul>
    19. 20. the skin condition <ul><li>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 . </li></ul>
    20. 21. compatibility with the intercellular lipids <ul><li>To do that we use Penetration enhancers witch is a substances that can partition into, and interact with, skin constituents . </li></ul>
    21. 22. thickness of the SC <ul><li>By increasing the thickness of the SC amount of water and lipid will increase and penetration of the skin increase. (sink condition) </li></ul><ul><li>My opinion </li></ul>
    22. 23. The moisture content <ul><li>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 . </li></ul><ul><li>(the mechanism by witch hydration increase skin penetration is not will understood) </li></ul><ul><li>Harry s cosmeticology (eighth edition ) page 352 </li></ul>
    23. 24. tempreture <ul><li>As the tempreture increases the penetration increase , because of : </li></ul><ul><li>1- lowering of the activity coefficient of pharmaceutical substances in the skin. </li></ul><ul><li>2- increases in drug solubility. </li></ul><ul><li>3- increase in diffusion and blood flow . </li></ul><ul><li>4- transition from gel to liquid crystal of layer lipid hydrocarbon chain will reduce the viscosity so increase the duffusion. </li></ul>
    24. 25. Penetration Enhancer <ul><li>There are more than one way to differentiate and classify skin penetration enhancer : </li></ul><ul><li>1 - classifying them according to the preferred rout of penetration. </li></ul><ul><li>2- according to carry different molecule . </li></ul><ul><li>3 - according to their mechanism of enhancement. </li></ul>
    25. 26. Penetration Enhancer according to the preferred rout of penetration <ul><li>1- solvent that enhance penetration through both polar and non-polar pathway. </li></ul><ul><li>2- enhancers that preferentially affect the polar route . </li></ul><ul><li>3- enhancer that mainly modify the non-polar route. </li></ul>
    26. 27. Penetration Enhancer according to the preferred rout of penetration <ul><li>1- solvent that enhance penetration through both polar and non-polar pathway such as: </li></ul><ul><li>2-pyrrolidone </li></ul><ul><li>b. N-methyl pyrrolidone </li></ul><ul><li>N-methyl-formaide </li></ul><ul><li>d. propylene glycol in combination with azon. </li></ul>
    27. 28. Penetration Enhancer according to the preferred rout of penetration <ul><li>2- enhancer that mainly modify the non-polar route, such as : </li></ul><ul><li>propylene glycol and oleic acid. </li></ul><ul><li>propylene glycol alone. </li></ul>
    28. 29. Penetration Enhancer according to the preferred rout of penetration <ul><li>3- enhancers that preferentially affect the polar route , such as: </li></ul><ul><li>a. Propylene glycol in combination with decylmethylsulfoxide. </li></ul>
    29. 30. Penetration Enhancer according to the preferred rout of penetration <ul><li>The 3 major mechanisms (polar) : </li></ul><ul><li>Extraction the SC lipids: (The permeability coefficient of polar molecule increased with increasing lipid extraction). </li></ul><ul><li>2. Inducing a relaxation of the polymeric structure of the cytoplasmic matrix in keratinocytes cell. </li></ul><ul><li>3. Changing the solvent properties of the SC. (surfactant) </li></ul>
    30. 31. Penetration Enhancer according to the preferred rout of penetration <ul><li>*Surfactant: </li></ul><ul><li>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 . </li></ul><ul><li>non-ionic surfactant were shown to shows fluidizing effect on the SC. </li></ul>
    31. 32. Penetration Enhancer according to their mechanism of enhancement. <ul><li>1- Enzyme . </li></ul><ul><li>2- Chemical enhancers . </li></ul><ul><li>3- Vesicular system . </li></ul><ul><li>4- Ceramides (one of the lipid classes in the SC). </li></ul>
    32. 33. (1) Enzyme <ul><li>Using an enzyme to affect the barrier properties of the SC refer to either affecting activity of : </li></ul><ul><li>1- enzyme present in the skin. </li></ul><ul><li>2- Or to enzyme applied to it from outside. </li></ul>
    33. 34. How dose the enzyme work ? <ul><li>1- by affecting the synthesis of lipid class in SC (fatty acid, cholesterol and ceramides), such as: </li></ul><ul><li>* 5-(tetradecyloxy)-2-furancarboxylic acid. this will prevent fatty acid synthesis. </li></ul><ul><li>* Fluvastatin . </li></ul><ul><li>this will prevent cholesterol synthesis . </li></ul>
    34. 35. How dose the enzyme work ? <ul><li>2-by affecting metabolism and biochemical cascade in the skin , such as: </li></ul><ul><li>* papian ; is a proteolytic enzyme , that increase the SC thickness , and the living epiderm. </li></ul>
    35. 36. How dose the enzyme work ? <ul><li>3- subtissues phase separation , lamellar bodies formation and created disorder in lamellar structures in the SC . </li></ul>
    36. 37. (2) Chemical enhancers <ul><li>Most chemical enhancers affect the intercellular lipid bilayers in the SC , it allows the creation of various types of (openings) in the bilayers. </li></ul><ul><li>Example: </li></ul><ul><li>* isopropyl myristate. </li></ul><ul><li>* isopropyl alcohol. </li></ul><ul><li>* oleic acid. </li></ul>
    37. 38. Chemical enhancers <ul><li>* oleic acid : </li></ul><ul><li>It was observed that oleic acid make alteration in the SC specifically in the intercellular spaces. </li></ul>
    38. 39. <ul><li>Another Chemical enhancers </li></ul>
    39. 40. Penetration enhancers ( DMSO) <ul><li>* Dimethyl sulfoxide (DMSO): </li></ul><ul><li>By changing in the conformation of the skin </li></ul><ul><li>Keratins from an α-helical to a β-sheet </li></ul><ul><li>Conformation ,that happen because of (DMSO </li></ul><ul><li>tended to bind to free water before the </li></ul><ul><li>protein-bound water was replaced and the </li></ul><ul><li>protein conformational changes were </li></ul><ul><li>induced. </li></ul>
    40. 41. Penetration enhancers (azon) <ul><li>Azone may act on the lipid-rich route because it fluidizes the stratum corneum lipids . </li></ul><ul><li>on the water-rich route because it enriches the water content . </li></ul><ul><li>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 skin barrier </li></ul>
    41. 42. (3) Vesicular system <ul><li>What is Vesicular system ? </li></ul><ul><li>It is an Encapsulation of the drug in vesicular structures such as liposomes . </li></ul>
    42. 43. (3) Vesicular system <ul><li>A major force driving vesicle penetration through the skin may be the water gradient across the epidermis. </li></ul>
    43. 44. (3) Vesicular system <ul><li>We have </li></ul><ul><li>* classic multi-layered phosphoplipid liposomes : </li></ul><ul><li>Act as a reservoir and would not be the carrier of choice. </li></ul><ul><li>* SC lipid-based liposomes : </li></ul><ul><li>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. </li></ul>
    44. 45. (3) Vesicular system <ul><li>On the another hand the scientist found that : </li></ul><ul><li>*phospholipids liposomes increase SC lipid bilayer disorder and increase permeation . </li></ul><ul><li>*SC lipid-based liposomes have a high affinity to the SC and generate a reservoir because it increase the order of the lipid in the intercellular lamellae . </li></ul>
    45. 46. (4) ceramides
    46. 47. (4) ceramides <ul><li>Ceramides in certain concentration were shown to create an imbalance in the intercellular lamellar organization and to enhance skin penetration . </li></ul><ul><li>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 primary alcohol. </li></ul>
    47. 48. <ul><li>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 </li></ul>
    48. 49. Summary <ul><li>We talk a bout four of the skin penetration pathways ( the intercellular pathway ,the intracellular pathway, the intrafollicular pathway and the </li></ul><ul><li>sebaceous glands pathway, and the polar pathway ) and four types of penetration enhancer ( enzymes, chemical enhancer , and the vesicular system , ceramides ) </li></ul>
    49. 50. THE END
    50. 51. References <ul><li> Cosmetic & toiletries magazine.(vol.120,No. 6/2005) </li></ul><ul><li> Delivery System Handbook for Personal Care and Cosmetic Products. By Meyer </li></ul><ul><li> Bos ,J.D., Meinardi ,M.M..(2000). The 500 Dalton rule for the skin penetration of chemical compounds and drugs. experimental terminology. 9(3), 165-9. </li></ul><ul><li> Harry s cosmeticology (eighth edition ) page 352 </li></ul><ul><li> Tanja ,M.Greve .Kristine ,B.Andersen ,Ole ,F.Nielsen2..(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. </li></ul><ul><li> Mechanism of skin penetration-enhancing effect by laurocapram (the name of article) </li></ul>

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