Transcript Topical drug delivery

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
--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 (< 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, 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.
Sunscreen agents
• SPF: Minimal, 2-12; Moderate, 12-30
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)
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.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
Grade
Qualitative description
Quantitative description
I
Comedonal acne
Comedones only, < 10 on face,
none on trunk, no scars, noninflammatory lesion
II
Papular
10-25 papules, mild scarring,
inflammatory lessoin (< 5 mm)
III
Pustule
25 pustules, moderate scarring
IV
Pustulocytic acne
Nodules or cysts, extensive
scarring, inflammatory lessions .
5 mm.
Cytic acne
Extensive 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
Decreasing the amount of sebum
produced
Unblocking the sebaceous ducts
Retenion hyperkeratosis
• Presence of
Propionibacterium acnes
P. acnes lipases break triglyceride to
fatty acids, which are irritating, causing
comedones.
Kill the bacteria
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
Prescription
• Tretinoin (retin-A):
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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)
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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.
http://www.poison-ivy.org/
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