Delivering Drugs Through Impermeable Barriers Flashcards
What is the structure of epidermis?
Stratum corneum
Stratum lucidum
Stratum granulosum
Stratum spinosum
Stratum basale
Basement membrane
Dermis
What are the different barriers?
Skin
BBB
Intestinal mucosal barrier
Paracellular + transcellular diffusion barrier
What are the challenges of impermeable barrier?
Lipid bilayers
Mucus
Enzyme transporters
What are the challenges of passive diffusion?
Macromolecules (eg. proteins, DNA)
Tight junction
Viscous mucus
What are the challenges of efflux mechanisms?
P-glycoprotein
Multidrug resistant proteins
What are the challenges of invasiveness?
Limitations of needle-based devices
What are the limitations of needle-based injections?
Specialist training
Invasive
Pain
Needle phobia
What is the injection degree for IM?
90
What is the injection degree for SC?
45
What is the injection degree for IV?
25
What is the injection degree for ID (intra-dermal)?
15
What are the chemical approaches (formulation-based) to overcome barriers?
Chemical penetration enhancers (CPEs)
Prodrug
Carrier
What are the physical approaches (device-based) to overcome barriers?
Iontophoresis
Electroporation
Ultrasound
Jet injector
Laser-assisted strategies
Microneedles
What are the job of CPE?
Modulate barrier function
How do pro-drugs work?
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
What is an example of a prodrug?
Enalapril
How do Enalapril work as a prodrug?
Higher intestinal permeability
Bioactivated in the liver
How does a codrug work (“mutual prodrug”)?
Releases active drug with no inactive by-product
What are the uses of a carrier?
Improve drug solubility/permeability
Control drug release
Improve drug targeting
What are the types of carriers?
Lipid vesicles - eg. micelles
Dendrimers
Nanoparticles - eg. nanospheres
Drug carrier conjugates - eg. cell-penetrating peptides
Viral carriers
What is sonophoresis for?
Ultrasound
Drug delivery in the skin
How does sonophoresis work?
Ultrasound
Ultrasound waves create vibration + heat
Acoustic cavitation
Increase kinetic energy
What is acoustic cavitation?
Ultrasound
Creation + subsequent collapse of microbubbles create shockwaves
= disrupt skin barrier = increase skin permeability
What is sonoporation?
Ultrasound
Drug delivery into cells across plasma membrane
What is iontophoresis?
Continuous electrical current applied across membrane barrier
For transdermal drug delivery
What is electrorepulsion?
Iontophoresis
Ionic drug propelled across membrane barrier
What is electroosmosis?
Iontophoresis
Electorepulsion creates solvent flow, which carries along dissolved neutral/polar molecules
What can the electrical field do?
Iontophoresis
Directly enhance membrane permeability, enhancing passive diffusion
What is electroporation?
Drug delivery into cells
= short, intense electrical impulses
How does electroporation work?
Destabilisation of lipid bilayer = transient pore formation
= drug diffuses passively through hydrophilic pores
What is a jet injector?
Injects medication across skin
What are the types of jet injectors?
Spring-loaded
Pressurised gas
What is the mechanism of jet injectors?
High pressure jet of liquid erodes membrane barrier
Can deliver range of doses
How does laser assisted strategies work?
Ablation
Enlargement of lacunar space
Thermal damage
What does laser assisted strategies do?
Improve skin permeability
Improve depth of drug penetration
What are microneedles?
Miniature needles
Minimally invasive
Patch or injector format
Dermal, ocular + oral drug delivery
What are solid microneedles?
Microneedle pre-treatment
Followed by topical application of drug
What are coated solid microneedles?
Drug formulation coats microneedle surface
What are dissolving solid microneedles?
Drug encapsulated with microneedles, which dissolve/biodegrade in membrane barrier
What are hydrogel-forming solid microneedles?
Drug diffuses into membrane from reservoir as hydrogel microneedles swell upon hydration
What are hollow microneedles?
Drug injected from reservoir through orifice in microneedles
What is bad about poke + flow microneedles?
Difficult to control amount
What is bad about coated microneedles?
Small SA = limited amount given
Sharp waste
What is bad about dissolving microneedles?
Not suitable for extended release
Limited amount of drug in needles
What is good about hydrogel microneedles?
Increased dose over an extended time
How would an oral insulin delivery work?
Needle in each pod
Come into correct contact with correct orientation
= inject insulin
