Topical drug delivery

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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

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Skin anatomy

• Epidermis
• --0.8 to 0.006 mm.
• --stratum corneum 10 mm when dry, horny layer
  (10-20 moisture)
• Dermis
• --3-5 mm
• --a matrix of connective tissues woven
  fibrous proteins
• --Nerves, blood vessels (lt 0.2 mm deep),
  lymphatics
• Subcutaneous tissue
• --mechanical cushion, thermal barrier, energy
  storage
• Appendages
• --Sweat glands
• --hair follicles
• --Sebaceous glands
• --Nails

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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

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Stages on percutaneous absorption from a
suspension ointment
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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

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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
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UV spectrum
Factors affecting exposure to UVR Time of the
day, Altitude, environmental factors, and
predisposed factors.
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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, 20-30 min, oxidation of melanin
  and dilation of dermal venules
• -- True sunburn erythema, 2-8 h
• -- Localized edema and pain, 14-20 h, last
  1-3 days
• Other reactions to UVR
• -- actinic keratosis, squamous cell
  carcinoma, basal cell carcinoma, melanoma.

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Sunscreen agents

• SPF Minimal, 2-12 Moderate, 12-30
• high, gt 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.
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Dihydroxyacetone (DHA)
Coppertone
Erythrulose
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.
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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

http//www.skincarephysicians.com/acnenet/acne.htm
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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.

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Assessment of acne severity
Self treatment with OTC agents is only OK for
grade I.
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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 Unblocki
ng the sebaceous ducts Kill the bacteria
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OTC acne product

• Benzoyl peroxide
• -- 2.5 to 10
• -- Most effective OTC
• -- Kill P. acnes and irritant to increase
  epithelial cell turnover rate.
• -- gel, cream, or lotion
• Salicylic acid
• -- 0.5-2, irritant keratolytic agent,
  lotion, creams
• Sulfur, 3-8 combined with resorcinol 2, or
  resorcinol monacetate 3.
• keratolytic and antibacteria, color/odor
• Resorcinol
• -- 1-4, keratolytic when combined with sulfur

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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

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Tretinoin is very effective
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Hair follicular cycle
Human Normally up to 90 of the hair follicles
are in anagen phase while, 1014 are in telogen
and 12 in catagen. Rodent hair follicles are
synchronized in the first two cycles.
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Hair follicles as a route for drug/vaccine
delivery
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Macromolecules access skin via hair follicles
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Contact dermatitisInflammation 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.

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Allergic contact dermatitis

• Hapten contacts skin epidermis
• Hapten complexes with protein
• Hapten-protein enters lymphatic systems
• Generation of specific Th1 CD4 and CD8 T cells.
• Re-exposure
• Dermatitis responses
• Urushiol from poison ivy, poison oak, and sumac.

Hapten small molecules that are only antigenic
when combined with a carrier protein.
http//www.poison-ivy.org/
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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.

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Topical corticosteriod preparations
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Some brand names of hydrocortisone