Lipid-Based Delivery Systems

Question 1

What are liposomes made of?

Answer 1

Lipids (hydrophilic head, hydrophobic tail), and surfactants, forming a bilayer to stabilise in water

Question 2

What does concentric mean?

Answer 2

Having 1 centre.

Question 3

How is each layer in a liposome separated?

Answer 3

By a water compartment, creating a hydrophobic environment.

Question 4

What is the function of cholesterol in liposomes?

Answer 4

It is an excipient and helps in packing the liposomes when administering them.

Question 5

What are the names given to one bilayer, and multiple bilayers of liposomes?

Answer 5

1. Vesicle = liposome
2. Lamellae = 1 bilayer
3. Multi lamellae vesicles (MLV)

Question 6

How can you prevent aggregation of liposomes?

Answer 6

1. Charging the suface of the liposome

2. Attach a PEG on the surface, so 2 liposomes cannot come together due to steric hindrance.

Question 7

How are liposomes classified?

Answer 7

By the number of layers they have, & their size (diameter).
<100nm = small vesicle
>100nm = large vesicle

Question 8

What are some characteristics of a liposomal bilayer?

Answer 8

1. Contains an aqueous core
2. They can be PEGylated to prevent liposome aggregation & prolong its half-life
3. Drug would be crystallised within the aq. fluid
4. Some can be attached with antibodies to target a specific site –>less side effects

Question 9

How can the half life of a liposome be prolonged?

Answer 9

1. PEGylation

2. Freeze drying them so only lipid sheets are present (like a solid powder)

Question 10

How are liposomes administered?

Answer 10

As IV injections/infusions, since they are suspended in water

Question 11

What monomer is used to make liposomes?

Answer 11

Phospholipids, derived from lecithin or hydrated soya

Question 12

Which part of the phospholipid allows its hydrophilic, and hydrophobic nature to occur?

Answer 12

Choline = hydrophilic nature

Alkyl chains = hydrophobic nature

Question 13

What is the critical packing parameter (CPP)?

Answer 13

CPP = V/a X l
It gives us a value to determine whether the vesicle will form a bilayer or not.

0.5-1 = bilayers form 
<0.5 = micelles form 
>1 = inverted micelles form

Question 14

What occurs in the lipid hydration method of liposome preparation?

Answer 14

Lipids in a flask are mixed with an organic solvent & aq. medium.
A 2 phase mixture is formed once you shake it.
Liposomes are then formed as a milky suspension.

Question 15

What occurs in the evaporation method of liposome preparation?

Answer 15

Lipids are freeze-dried to remove water, so a powder is obtained.
it is then reconstituted with water when administered.

Question 16

What occurs in the sonication method of lipid preparation?

Answer 16

Large liposomes are broken up into smaller ones

Question 17

Why must the phase transition temperature (i.e. melting point) be >60 when working with bilayers?

Answer 17

To allow the lipids to open up and obtain the liposomes.

>60 degrees would form a liquid crystalline phase

Question 18

What factors can affect the releasing characteristics of a drug in a liposome?

Answer 18

1. Solute
2. Liquid surfactant used
3. Surface charge - use an oppositely charged lipid
4. Cholesterol content
5. Size of vesicle - too big can block blood vessels

Question 19

What are the 3 methods for controlling the size of vesicle?

Answer 19

1. Fractionation - either centrifugation or size-exlusion chromatography
2. Sonication
3. Extrusion

Question 20

What occurs in fractionation for vesicle sizing?

Answer 20

EITHER:

1. Centrifugation - spinning liposomes, so light ones end up at the top & larger ones at the bottom
2. Size-exlusion chromatography - as above

Question 21

What occurs in the extrusion process of vesicle sizing?

Answer 21

Different pores sizes are present, and a syringe on either side pumps in liposomes into the extrusion membrane.

Liposomes are eventually broken down into the size of the pores

Question 22

What are some examples of drugs which use a lipid formulation?

Answer 22

1. Doxorubicin
2. Cytarabine
3. AmBisome
4. Epaxal

Question 23

What is Caelyx?

Answer 23

It is a sterile, red liposomal dispersion anti-cancer drug optimised for targeted delivery. The surface is also PEGylated for a longer circulation time.

Question 24

What is a STEALTH liposome? What is an example of one?

Answer 24

A liposome which is PEGylated, and remains in the blood but are not detected by immune cells.

An example is Caelyx (doxorubicin)