Lecture 13C - Use of Liposomes

Question 1

What are liposomes?

Answer 1

spherical vesicles in which a lipid bilayer membrane delimitates a central aqueous compartment

Question 2

What can liposomes carry?

Answer 2

hydrophilic and hydrophobic drugs

Question 3

When do liposomes form?

Answer 3

when the phospholipids are exposed to an aqueous environment

Question 4

Where are hydrophilic drugs carried in a liposome?

Answer 4

in the aqueous compartment

Question 5

Where are lipophilic drugs carried in a liposome?

Answer 5

in the lipid bilayer membrane

Question 6

What is fungizone?

Answer 6

amphotericin (antifungal agent used to treat invasive fungal infections such as candidiasis

sterile lyophilised powder

Question 7

Fungizone after reconstitution?

Answer 7

micellar dispersion of amphotericin and sodium deoxycholate (surfactant)

Question 8

How is fungizone administered?

Answer 8

as an IV infusion over 20-30 mins

Question 9

What is a micelle?

Answer 9

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

Question 10

What are the problems of fungizone?

Answer 10

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)

Question 11

What does amphotericin bind to?

Answer 11

ergosterol present in fungal cell membranes

Question 12

What causes toxicity of amphotericin?

Answer 12

Binds to cholesterol in mammalian healthy cell membranes

rapid release of the drug = toxicity on mammalian cells

Question 13

What is ambisome?

Answer 13

small unilamellar vesicle

single bilayer
less than 100nm

Question 14

How is the drug formulated in ambisome?

Answer 14

drug intercalated within the liposome membrane

Question 15

Disadvantage of ambisome?

Answer 15

following IV injection, interaction with blood opsonins

this causes removal from the circulation

Question 16

Where do the liposomes in ambisome end up?

Answer 16

in the tissues on the mononuclear phagocytosis system, mostly fixed to macrophages in the liver and spleen

Question 17

Advantages of ambisome?

Answer 17

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

Question 18

How much less toxic is ambisome than fungizone?

Answer 18

~80 times less toxic

Question 19

What improves the therapeutic index of amphotericin?

Answer 19

when formulated as a liposome

Question 20

Improved clinical efficacy of ambisome?

Answer 20

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

Question 21

When is ambisome used?

Answer 21

the last resource for a patient suffering from a serious infection

Question 22

What is the problem for fungizone vs ambisome?

Answer 22

fungizone is much cheaper

1 vial of fungizone = £6
1 vial of ambisome = £150