Function (& Dysfunction) of the Skin

Question 1

Skin as a barrier

Answer 1

5 barriers

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

Question 2

Wound repair in skin

Answer 2

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 3

Transdermal drug delivery systems

Answer 3

Skin is easily accessible and a potentially non-invasive route to delivering drugs

Transdermal drug delivery: 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

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

Question 4

Stratum corneum: bricks and mortar

Answer 4

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 5

Transdermal drug delivery systems

Answer 5

Active delivery: Disruption of the stratum corneum
Passive delivery: Do not disrupt the stratum corneum

Active delivery methods;

Iontophoresis: moving ions across the membrane
Sonophoresis: using ultrasound to improve drug delivery

Electroporation: creating pores in the SC using electric impulses
Photomechanical waves: using photodynamic waves to penetrate the SC

Microneedle: needles pierce the superficial layer of skin

Thermal ablation: localised heat to create microchannels in skin

Question 6

Fentanyl ITS

Answer 6

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 7

Botulinum Toxin Type A

Answer 7

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

Question 8

Transdermal drug delivery systems- passive

Answer 8

Active delivery: Disruption of the stratum corneum
Passive delivery: Do not disrupt the stratum corneum

Passive delivery methods;
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 9

BuTrans skin patch

Answer 9

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 10

Lipid nanoparticles

Answer 10

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 11

Hair

Answer 11

Transappendageal/ transfollicular: Part of the integumentary system
Hairy skin covers 90% of the body

Question 12

Nails

Answer 12

Transungual drug delivery
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 13

3D printing

Answer 13

3D print implantable biomaterials
Precision control (avoid human error)
Rapid
Match patient wound-site geometry

Bioprinting: Combining material and cells in a printable ‘ink’