Lipid-Based Delivery Systems Flashcards
What are liposomes made of?
Lipids (hydrophilic head, hydrophobic tail), and surfactants, forming a bilayer to stabilise in water
What does concentric mean?
Having 1 centre.
How is each layer in a liposome separated?
By a water compartment, creating a hydrophobic environment.
What is the function of cholesterol in liposomes?
It is an excipient and helps in packing the liposomes when administering them.
What are the names given to one bilayer, and multiple bilayers of liposomes?
- Vesicle = liposome
- Lamellae = 1 bilayer
- Multi lamellae vesicles (MLV)
How can you prevent aggregation of liposomes?
- Charging the suface of the liposome
2. Attach a PEG on the surface, so 2 liposomes cannot come together due to steric hindrance.
How are liposomes classified?
By the number of layers they have, & their size (diameter).
<100nm = small vesicle
>100nm = large vesicle
What are some characteristics of a liposomal bilayer?
- Contains an aqueous core
- They can be PEGylated to prevent liposome aggregation & prolong its half-life
- Drug would be crystallised within the aq. fluid
- Some can be attached with antibodies to target a specific site –>less side effects
How can the half life of a liposome be prolonged?
- PEGylation
2. Freeze drying them so only lipid sheets are present (like a solid powder)
How are liposomes administered?
As IV injections/infusions, since they are suspended in water
What monomer is used to make liposomes?
Phospholipids, derived from lecithin or hydrated soya
Which part of the phospholipid allows its hydrophilic, and hydrophobic nature to occur?
Choline = hydrophilic nature
Alkyl chains = hydrophobic nature
What is the critical packing parameter (CPP)?
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
What occurs in the lipid hydration method of liposome preparation?
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.
What occurs in the evaporation method of liposome preparation?
Lipids are freeze-dried to remove water, so a powder is obtained.
it is then reconstituted with water when administered.
What occurs in the sonication method of lipid preparation?
Large liposomes are broken up into smaller ones
Why must the phase transition temperature (i.e. melting point) be >60 when working with bilayers?
To allow the lipids to open up and obtain the liposomes.
>60 degrees would form a liquid crystalline phase
What factors can affect the releasing characteristics of a drug in a liposome?
- Solute
- Liquid surfactant used
- Surface charge - use an oppositely charged lipid
- Cholesterol content
- Size of vesicle - too big can block blood vessels
What are the 3 methods for controlling the size of vesicle?
- Fractionation - either centrifugation or size-exlusion chromatography
- Sonication
- Extrusion
What occurs in fractionation for vesicle sizing?
EITHER:
- Centrifugation - spinning liposomes, so light ones end up at the top & larger ones at the bottom
- Size-exlusion chromatography - as above
What occurs in the extrusion process of vesicle sizing?
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
What are some examples of drugs which use a lipid formulation?
- Doxorubicin
- Cytarabine
- AmBisome
- Epaxal
What is Caelyx?
It is a sterile, red liposomal dispersion anti-cancer drug optimised for targeted delivery. The surface is also PEGylated for a longer circulation time.
What is a STEALTH liposome? What is an example of one?
A liposome which is PEGylated, and remains in the blood but are not detected by immune cells.
An example is Caelyx (doxorubicin)
