Skin delivery Flashcards
Which are the 3 routes of delivery across skin?
Transcellular: Through cells in stratum corneum
Intercellular: Around cells in stratum corneum
Transappendegeal: In through hair follicles and sweat glance
What is the stratum corneum? How is its structure?
A part of the epidermis layer of the skin, consisting of keratinocytes and lipids.
15 layers, 70 nm thickness and 36 nm pores to go through.
Summarize two main avenues for enhancing permeability across skin. Give at least two examples for each strategy
Physical distrubtion: Needles, laser, electroporation, ultrasound – make holes (microneedles)
Chemical distrubtion: Dissolve lipid layer in stratum corneum with solvents
What are the size limits and other physiochemical properties needed for NPs passage across intact skin into viable tissues with each of the three routes?
Transcellular: Small (20 nm), hydrophobic and uncharged particles - get into the cells.
Intercellular: Small enough to fit through the pores (<20 nm)
Transappendageal: 200 nm to get in through hair follicles and glands, but not go any further (<20 nm here as well?)
Describe the type, composition and benefits of nanoemulsions, and name the four subtypes.
General: Nanoscale oil-in-water or water-in-oil structures based on amphiphilic molecules.
+ Ease of preparation, solubilization of drugs in the hydrophobic core, increases permeability through the skin
Nanomicelles, liposomes, niosomes and pickering emulsions
Name 2 low energy self-assembly methods of nanoemulsion preparation. What are the differences between these methods?
Emulsion Inversion Point, EIP (dilute until system of small nanodroplets).
Phase Inversion Temperature, PIT (heat up to invert phase, cool down to invert back but smaller particles).
EIP constant temperature, PIT changing temperature.
Give at least one example of a method for manufacturing liposomes.
Hydration of dry lipid film: Dry lipid with solvent evaporation > film on bottom > add water > fold over > liposomes
Which method can be used for controlling the size of liposomes?
Sonication
Define edge-activators and explain their role in producing liposomes. Give at least 2 examples of edge-activator molecules.
Increase the flexibility in liposomes, make more flexible – go easier small openings
Ethanol and cholesterol, charged and non-ionic surfactants
Define Pickering emulsions. How can they be used in life sciences context?
Emulsions stabilized by NPs on the interface between to phases
Usedul when we don’t want to use surfactant, need slower release of cargo, sustained drug release, or depear penetration
What is the rationale for using inorganic NPs (TiO2; ZnO) as sunscreens? Elaborate on the nano-aspect (give at least 3 benefits)
Multiple mechanisms: Reflect, scatter and absorb UV
Not systemic, do not go into cells as easy (unlike organic)
Transparent
Broader absorption range of UV
What are micelles and what are their benefits?
Monolayer, hydrophobic core, single chain surfactant.
+ Topical use (low penetration)
What are liposomes and what are their benefits?
Bilayers with phosphoplidpids (neutral/charged), double chain surfactant, hydrophilic core
+ More stable than micelles, longer penetration
What are niosomes and what are their benefits?
Bilayers with synthtetic neutral molecules, single chain surfactant
+ High purity, cheap and stability
What are pickering emulsions and what are their benefits?
Particle held together by NPs on the interface of oil and water. Which type of particle depends on contact angle (<90 oil-in-water, “NP from water phase”)
