Function (& Dysfunction) of the Skin

Question 1

skin barrier

Answer 1

microbial barrier, physical barrier, chemical barrier, immunological barrier, neuro-sensory

Question 2

Atopic Dermatitis (AD)- break down of skin barrier

Answer 2

Chronic, recurrent and inflammatory disease of the skin
Affects both children and adults (though higher in children)

Question 3

Healthy SC- breakdown of the skin barrier

Answer 3

Corneocytes (keratin-rich differentiated keratinocytes) are held together by corneodesmosomes with the space in between filled with lipid-rich matrix
The lipid matrix prevents transepidermal water loss

Question 4

Wound repair in skin

Answer 4

Haemostasis: Vasoconstriction of blood vessels and platelet aggregation to stop bleeding
Inflammation: Influx of cells to begin inflammatory process (neutrophil and macrophage differentiation)
Proliferation: Formation of granulation tissue
Maturation: Strengthening the matrix

Question 5

Transdermal drug delivery

Answer 5

non-invasive delivery of drugs via absorption for a variety of reasons: pain relief, hormone therapy, diseases of the cardiovascular and central nervous systems etc.
No loss due to first-pass metabolism
No interference from pH, enzymes, intestinal bacteria
Minimal burden on patient
Can be used for all ages

Question 6

route of Transdermal drug delivery systems

Answer 6

Intercellular: In between cells (predominant pathway)
Intracellular: Through cells
Follicular: Through hair follicles

Question 7

Stratum corneum: bricks and mortar

Answer 7

Bricks: Corneocytes (terminally differentiated flat keratinocytes filled with keratin)
Corneodesmosomes link the ‘bricks’
Mortar: Lipid matrix (a mixture of ceramides, cholesterol and free fatty acids)

Hydrophobic drugs can travel 
through the ‘mortar’ while 
hydrophilic drugs travel mainly 
via the ‘bricks’ (though they still 
have lipid-rich mortar to navigate 
through)

Question 8

Active delivery-Transdermal drug delivery systems

Answer 8

Disruption of the stratum corneum

Question 9

Passive delivery-Transdermal drug delivery systems

Answer 9

Do not disrupt the stratum corneum

Question 10

Iontophoresis:

Answer 10

moving ions across the membrane

Question 11

Sonophoresis:

Answer 11

using ultrasound to improve drug delivery

Question 12

Electroporation

Answer 12

creating pores in the SC using electric impulses

Question 13

Photomechanical waves

Answer 13

using photodynamic waves to penetrate the SC

Question 14

Microneedle

Answer 14

needles pierce the superficial layer of skin

Question 15

Thermal ablation

Answer 15

localised heat to create microchannels in skin

Question 16

Fentanyl ITS

Answer 16

ITS: iontophoretic transdermal system
Management of acute, moderate-to-severe postoperative pain

Self-administered pre-programmed doses of fentanyl delivered non-invasively (low-	intensity electric current) to transport ionised drug molecules actively through 	skin into 	systemic system

Increase patient compliance: ease of use and automatic reminders to change dosages

Question 17

Botulinum Toxin Type A

Answer 17

To treat sweaty palms (hyperhidrosis): overactive sweat glands on palms of hands
Drug: Botulinum toxin
Solid microneedle delivery
Phase I clinical trials complete

Question 18

Transdermal drug delivery systems-Passive delivery methods

Answer 18

Vesicles: water filled particles with a bilayer to carry drugs
Polymer nanoparticles: >1000nm to control release and extend residence time
Nanoemulsion: mixture of oil and water

Question 19

BuTrans skin patch

Answer 19

Strong opioid used to treat opioid use disorders but also strong painkiller
Active ingredient: buprenorphine

A transdermal patch: potent low MW analgesic acting on the 
central nervous system suspended in polymer patch 

High-affinity binding to mu-opioid receptors and 
slow-dissociation kinetics (unlike agonists like morphine 
and fentanyl) allowing withdrawal symptoms to be 
milder/ less uncomfortable for patients

Question 20

Lipid nanoparticles

Answer 20

Can easily travel through the ‘mortar’ of the epidermis

Companies are using modified lipid nanoparticles for targeted therapies
E.g., gene therapy (traditionally viral vehicles but these are difficult to scale-up)

Question 21

Transungual drug delivery

Answer 21

Not hugely popular but…
A good way of treating fungal nail infections and avoiding liver toxicity and first pass metabolism

Nail composed of cross-linked keratin is difficult to penetrate
Chemical penetration enhancers to weaken nail structure
Etching, iontophoresis and ultrasound to mediate drug delivery
Lacquers: nail varnish with antimycotic 
agents

Question 22

Personalised biomedical devices

Answer 22

Soft implantable drug delivery device to treat epilepticus (fatal epileptic condition)
Wireless monitoring triggering subcutaneous drug release