Lecture 13C - Use of Liposomes Flashcards
What are liposomes?
spherical vesicles in which a lipid bilayer membrane delimitates a central aqueous compartment
What can liposomes carry?
hydrophilic and hydrophobic drugs
When do liposomes form?
when the phospholipids are exposed to an aqueous environment
Where are hydrophilic drugs carried in a liposome?
in the aqueous compartment
Where are lipophilic drugs carried in a liposome?
in the lipid bilayer membrane
What is fungizone?
amphotericin (antifungal agent used to treat invasive fungal infections such as candidiasis
sterile lyophilised powder
Fungizone after reconstitution?
micellar dispersion of amphotericin and sodium deoxycholate (surfactant)
How is fungizone administered?
as an IV infusion over 20-30 mins
What is a micelle?
assembly of surfactant molecules in water, with the hydrophilic head regions in contact with the surrounding solvent and the hydrophobic tail regions in the micelle centre
What are the problems of fungizone?
severe adverse side effects
renal toxicity (>80% patients, dose related and often irreverible)
haematological toxicity(thrombocytopenia, leukopenia, haemoglobin reduction)
CV toxicity (potentially fatal cardiac or cardiorespiratory arrest)
What does amphotericin bind to?
ergosterol present in fungal cell membranes
What causes toxicity of amphotericin?
Binds to cholesterol in mammalian healthy cell membranes
rapid release of the drug = toxicity on mammalian cells
What is ambisome?
small unilamellar vesicle
single bilayer
less than 100nm
How is the drug formulated in ambisome?
drug intercalated within the liposome membrane
Disadvantage of ambisome?
following IV injection, interaction with blood opsonins
this causes removal from the circulation
Where do the liposomes in ambisome end up?
in the tissues on the mononuclear phagocytosis system, mostly fixed to macrophages in the liver and spleen
Advantages of ambisome?
liposomes and fungi are taken up by the same mechanism
passive targeting of the liposomes to the infected organs
minimal exposure of non-target tissues
How much less toxic is ambisome than fungizone?
~80 times less toxic
What improves the therapeutic index of amphotericin?
when formulated as a liposome
Improved clinical efficacy of ambisome?
slow dissolution of amphotericin from liposome
prolonged circulation of ambisome in vivo
direct interaction of ambisome with fungal cells
minimal interaction of ambisome with mammalian cells
When is ambisome used?
the last resource for a patient suffering from a serious infection
What is the problem for fungizone vs ambisome?
fungizone is much cheaper
1 vial of fungizone = £6
1 vial of ambisome = £150
