Topical drug delivery Skin anatomy Functions of skin Five main target regions in dermatological therapy Sunscreen on skin surface Acne to target hair follicles and pilosebaceous unites Delivery of macromolecules via the hair follicles Contact dermatitis and viable epidermis and dermis

Skin anatomy Epidermis to mm. --stratum corneum: 10  m when dry, horny layer (10-20% moisture) Dermis mm --a matrix of connective tissues woven fibrous proteins --Nerves, blood vessels (< 0.2 mm deep), lymphatics Subcutaneous tissue --mechanical cushion, thermal barrier, energy storage Appendages --Sweat glands --hair follicles --Sebaceous glands --Nails

Functions of skin Mechanical function -- mainly from the dermis and s.c. tissues -- epidermis (minor) Protective function -- Microbiological barrier -- Chemical barrier -- Radiation barrier -- Heat barrier/temperature regulation -- Immune response

Stages on percutaneous absorption from a suspension ointment

Five main target regions in dermatology Surface treatment -- Camouflage, protective layer, insect repellent, antimicrobial/antifungal, Sunscreen Stratum corneum -- Emollient, keratosis Skin appendage -- Acne, antibiotics, depilatory, antiperspirant, vaccine Viable epidermis/dermis -- antiinflammation, anesthetics, antihistamine, antipruritic Systemic treatment -- transdermal

Sunlight, sunscreen, suntan UVA: suntan, and PUVA treatment of psoriasis (psoralen + UVA), photosensitivity, photoaging, photodermatoses, and augment cancerous effects of UVB. UVB: Vitamin D synthesis Cause sunburn, skin cancers UVC

UV spectrum Factors affecting exposure to UVR Time of the day, Altitude, environmental factors, and predisposed factors.

Suntan and sunburn Sun tanning: a result of two processes -- Oxidation of melanin/immediate darkening -- Stimulation of melanocytes/delayed tanning Tanning increases tolerance to additional sun light. Sunburn: a superficial burn involving the epidermis. -- Normal sequence -- Erythema, min, oxidation of melanin and dilation of dermal venules -- True sunburn erythema, 2-8 h -- Localized edema and pain, h, last 1-3 days Other reactions to UVR -- actinic keratosis, squamous cell carcinoma, basal cell carcinoma, melanoma.

Sunscreen agents SPF: Minimal, 2-12; Moderate, high, > 30 SPF is the minimal erythema dose (MED) of protected skin over the MED of unprotected skin. MED is the amount of solar radiation needed to produce minimal skin redness. Types of sunscreens Physical sun blockers Titanium dioxide, Zinc oxide, Red petrolatum Chemical sun absorbers (1) PABA (2) Cinnamates (3) Salicylates (4) Benzophenones (5) Avobenzone (Parsol 1789) Physical blockers are opaque formulations that reflect and scatter up to 99% of light in both VR and vis ranges. Less cosmetically acceptable/greasy. Sunscreens just need to bind and remain on the skin for sufficient time.

Dihydroxyacetone (DHA) Erythrulose Coppertone DHA is a chemical agent that darkens the skin by reacting with keratin in the stratum corneum to produce artificial suntan. It provides no protection against UV rays, and may not be natural looking. The Eryhtrulose is also in some products. It can be in lotion, gel, spray, solution, etc.

Acne Acne vulgaris is a disorder of the pilosebaceous units. A plug of the pilosebaceous duct and follicle opening. Drugs have to get into the hair follicles and pilosabaceous units /acnenet/acne.html

Etiology Increased sebum production Androgens regulate sebum production. Testosterone converted to DHT, which induces sebaceous glands to increase in size and activity, resulting in increased amount of sebum. Abnormal clumping of epithelial horny cells in the pilosebaceous unit Horny cells usually sloughed off from epithelial lining of the pilosebaceous duct. Retention hyperkeratosis (increased adherence and production of follicular epithelial cells) Presence of Propionibacterium acnes P. acnes lipases break triglyceride to fatty acids, which are irritating, cause comedones, and result in inflammation.

Assessment of acne severity GradeQualitative descriptionQuantitative description IComedonal acneComedones only, < 10 on face, none on trunk, no scars, non- inflammatory lesion IIPapular10-25 papules, mild scarring, inflammatory lessoin (< 5 mm) IIIPustule  25 pustules, moderate scarring IVPustulocytic acneNodules or cysts, extensive scarring, inflammatory lessions. 5 mm. Cytic acneExtensive nodule/cysts Self treatment with OTC agents is only OK for grade I.

Approaches for treatment Increased sebum production Testosterone converted to DHT, which induces sebaceous glands size and activity. Abnormal clumping of epithelial horny cells in the pilosebaceous unit Retenion hyperkeratosis Presence of Propionibacterium acnes P. acnes lipases break triglyceride to fatty acids, which are irritating, causing comedones. Decreasing the amount of sebum produced Unblocking the sebaceous ducts Kill the bacteria

OTC acne product Benzoyl peroxide % to 10% -- Most effective OTC -- Kill P. acnes and irritant to increase epithelial cell turnover rate. -- gel, cream, or lotion Salicylic acid %, irritant keratolytic agent, lotion, creams Sulfur, 3-8% combined with resorcinol 2%, or resorcinol monacetate 3%. keratolytic and antibacteria, color/odor Resorcinol %, keratolytic when combined with sulfur

Prescription Tretinoin (retin-A): increase the turnover rate of nonadhering horny cells in follicles. Cream, gel, topical solution More effective agent for acne Increase hair growth Others: Adapalene (Differin), Tazarotene gel and cream (Tazorac), antibiotics (tetracyline, erythromycin, clindamycin, etc) Isotretinoin (Accutane) For severe racalcitrant nodulocytic acnes Decrease sebum and keratinization Reduce population of P. acnes Birth defect

Tretinoin is very effective

Hair follicular cycle Human: Normally up to 90% of the hair follicles are in anagen phase while, 10– 14% are in telogen and 1–2% in catagen. Rodent: hair follicles are synchronized in the first two cycles.

Hair follicles as a route for drug/vaccine delivery

Macromolecules access skin via hair follicles

Contact dermatitis: Inflammation of the skin Irritant contact dermatitis Caused by direct contact with the irritant Absolute primary irritants: acids, alkalis, industrial chemicals, Relative primary irritants: soaps, detergent, benzoyl peroxide, etc) Allergic contact dermatitis: The result of direct contact with a contact allergen, such as poison ivy and nickel. Allergic contact dermatitis is considered a T-cell mediated delayed-response immune reaction, because elicitation of an allergic reaction typically takes 48 to 72 hours to occur after reexposure to the same allergen.

Allergic contact dermatitis 1.Hapten contacts skin epidermis 2.Hapten complexes with protein 3.Hapten-protein enters lymphatic systems 4.Generation of specific Th1 CD4+ and CD8+ T cells. 5.Re-exposure 6.Dermatitis responses Urushiol from poison ivy, poison oak, and sumac. Hapten = small molecules that are only antigenic when combined with a carrier protein.

Treatments Severe eruptions: systemic corticosteriods Less severe eruptions: Relieve itching Local anesthetics (benzocaine) Antihistamines (oral or topical, mainly sedative effect) Topical hydrocortisone Treatment Topical hydrocortisone.

Topical corticosteriod preparations

Some brand names of hydrocortisone