Delivering Drugs Through Impermeable Barriers

Question 1

What is the structure of epidermis?

Answer 1

Stratum corneum
Stratum lucidum
Stratum granulosum
Stratum spinosum
Stratum basale
Basement membrane
Dermis

Question 2

What are the different barriers?

Answer 2

Skin
BBB
Intestinal mucosal barrier
Paracellular + transcellular diffusion barrier

Question 3

What are the challenges of impermeable barrier?

Answer 3

Lipid bilayers
Mucus
Enzyme transporters

Question 4

What are the challenges of passive diffusion?

Answer 4

Macromolecules (eg. proteins, DNA)
Tight junction
Viscous mucus

Question 5

What are the challenges of efflux mechanisms?

Answer 5

P-glycoprotein
Multidrug resistant proteins

Question 6

What are the challenges of invasiveness?

Answer 6

Limitations of needle-based devices

Question 7

What are the limitations of needle-based injections?

Answer 7

Specialist training
Invasive
Pain
Needle phobia

Question 8

What is the injection degree for IM?

Answer 8

90

Question 9

What is the injection degree for SC?

Answer 9

45

Question 10

What is the injection degree for IV?

Answer 10

25

Question 11

What is the injection degree for ID (intra-dermal)?

Answer 11

15

Question 12

What are the chemical approaches (formulation-based) to overcome barriers?

Answer 12

Chemical penetration enhancers (CPEs)
Prodrug
Carrier

Question 13

What are the physical approaches (device-based) to overcome barriers?

Answer 13

Iontophoresis
Electroporation
Ultrasound
Jet injector
Laser-assisted strategies
Microneedles

Question 14

What are the job of CPE?

Answer 14

Modulate barrier function

Question 15

How do pro-drugs work?

Answer 15

Inactive pro-moiety bonded to active drug via temporary linkage
Biotransformation = labile bond cleaved in vivo
= releases active drug
Pro-moiety non-toxic + rapidly excreted

Question 16

What is an example of a prodrug?

Answer 16

Enalapril

Question 17

How do Enalapril work as a prodrug?

Answer 17

Higher intestinal permeability
Bioactivated in the liver

Question 18

How does a codrug work (“mutual prodrug”)?

Answer 18

Releases active drug with no inactive by-product

Question 19

What are the uses of a carrier?

Answer 19

Improve drug solubility/permeability
Control drug release
Improve drug targeting

Question 20

What are the types of carriers?

Answer 20

Lipid vesicles - eg. micelles
Dendrimers
Nanoparticles - eg. nanospheres
Drug carrier conjugates - eg. cell-penetrating peptides
Viral carriers

Question 21

What is sonophoresis for?
Ultrasound

Answer 21

Drug delivery in the skin

Question 22

How does sonophoresis work?
Ultrasound

Answer 22

Ultrasound waves create vibration + heat
Acoustic cavitation
Increase kinetic energy

Question 23

What is acoustic cavitation?
Ultrasound

Answer 23

Creation + subsequent collapse of microbubbles create shockwaves
= disrupt skin barrier = increase skin permeability

Question 24

What is sonoporation?
Ultrasound

Answer 24

Drug delivery into cells across plasma membrane

Question 25

What is iontophoresis?

Answer 25

Continuous electrical current applied across membrane barrier For transdermal drug delivery

Question 26

What is electrorepulsion? Iontophoresis

Answer 26

Ionic drug propelled across membrane barrier

Question 27

What is electroosmosis? Iontophoresis

Answer 27

Electorepulsion creates solvent flow, which carries along dissolved neutral/polar molecules

Question 28

What can the electrical field do? Iontophoresis

Answer 28

Directly enhance membrane permeability, enhancing passive diffusion

Question 29

What is electroporation?

Answer 29

Drug delivery into cells = short, intense electrical impulses

Question 30

How does electroporation work?

Answer 30

Destabilisation of lipid bilayer = transient pore formation = drug diffuses passively through hydrophilic pores

Question 31

What is a jet injector?

Answer 31

Injects medication across skin

Question 32

What are the types of jet injectors?

Answer 32

Spring-loaded Pressurised gas

Question 33

What is the mechanism of jet injectors?

Answer 33

High pressure jet of liquid erodes membrane barrier Can deliver range of doses

Question 34

How does laser assisted strategies work?

Answer 34

Ablation Enlargement of lacunar space Thermal damage

Question 35

What does laser assisted strategies do?

Answer 35

Improve skin permeability Improve depth of drug penetration

Question 36

What are microneedles?

Answer 36

Miniature needles Minimally invasive Patch or injector format Dermal, ocular + oral drug delivery

Question 37

What are solid microneedles?

Answer 37

Microneedle pre-treatment Followed by topical application of drug

Question 38

What are coated solid microneedles?

Answer 38

Drug formulation coats microneedle surface

Question 39

What are dissolving solid microneedles?

Answer 39

Drug encapsulated with microneedles, which dissolve/biodegrade in membrane barrier

Question 40

What are hydrogel-forming solid microneedles?

Answer 40

Drug diffuses into membrane from reservoir as hydrogel microneedles swell upon hydration

Question 41

What are hollow microneedles?

Answer 41

Drug injected from reservoir through orifice in microneedles

Question 42

What is bad about poke + flow microneedles?

Answer 42

Difficult to control amount

Question 43

What is bad about coated microneedles?

Answer 43

Small SA = limited amount given Sharp waste

Question 44

What is bad about dissolving microneedles?

Answer 44

Not suitable for extended release Limited amount of drug in needles

Question 45

What is good about hydrogel microneedles?

Answer 45

Increased dose over an extended time

Question 46

How would an oral insulin delivery work?

Answer 46

Needle in each pod Come into correct contact with correct orientation = inject insulin