Liposomal Drug Release (G4)

Question 1

What is an amphiphilic molecule?

Answer 1

• A molecule made up of 2 parts, a hydrophilic and hydrophobic part

Question 2

Under what conditions are micelles formed?

Answer 2

In aqueous solutions, amphiphilic molecules (have a hydrophilic and phobic part) form micelles when their concentration becomes larger than the critical micellar concentration

Question 3

What is the difference between a micelle, a vesicle and an emulsion drop?

Answer 3

• Emulsion droplets are significantly larger
• Vesicles have a lipid bilayer, while the others have a single layer of amphiphilic molecules

Question 4

Describe the structure of a liposome

Answer 4

• Spherical structure composed of single or multiple concentric bilayers
• Bilayers consist of a series of phospholipids assembled with polar heads at the surface and hydrophobic tails toward the inner of the bilayer

Question 5

What are the names given to liposome structures with 1, a few or many structured lipid bilayers?

Answer 5

Question 6

Aside from multiple bilayers, how else can liposomes vary in morphology?

Answer 6

• comprised of different sized vesicles
• the lipid bilayer consisting of different amphiphilic molecules

Question 7

What is the size classification of liposomes?

Answer 7

Question 8

Describe the structure of a phospholipid

Answer 8

• 1 glycerol bonded to
• 2 fatty acid tails and
• a phosphate group

Question 9

What is special about phosphatidyl choline and phosphatidyl serine and describe their structure

Answer 9

• They are derivatives of phospholipids but more efficient at forming bilayers
• Exactly the same as a phospholipid structure except a the alcohol group of the choline or serine group bound onto the alcohol group of the phosphate head, releasing H2O product

Question 10

What are the 2 release mechanisms of the active ingredient from a liposome?

Answer 10

1. Fusion of liposome bilayer with the cell membrane
2. Diffusion through a carrier protein in the membrane

Question 11

What is a stealth liposome? And the benefits of it

Answer 11

A stealth liposome is a liposome that has been modified to evade the detection by the bodys immune system
- This results in extended circulation time, and by extension increased therapeutic efficiency and drug delivery

Question 12

What is a targeted liposome? and the benefits of using them?

Answer 12

• This is a liposome that has been modified to have specific target ligands/antibodies on the surface that bind to a specific receptors on target cells
• Increases precision and efficiency of drug delivery to target tissues while reducing side effects to non-target areas

Question 13

What is a cationic liposome? and the benefits of them?

Answer 13

• A liposome with a positively charged surface due to the presence of cationic lipids (+ly charged) making up the bilayer.
• phosphatidyl choline is a commonly used cationic lipid
• These are used because positively charged liposomes can facilitate favourable reactions with Negatively charged molecules like DNA and RNA.
• Cationic liposomes exhibit increased stability and longer shelf life

Question 14

What is a PEGylated liposome used for?

Answer 14

• Utilised for delivery of specific cancer cell targeting drugs
• They are liposomes modified to have PEG chains on their surface
• This increases their stability, stealth and time in the circulation leading to a longer and better therapeutic effect
• They can also permeate more into cancer cells

Question 15

What is the mechanism behind, Antibody-directed enzyme prodrug therapy (ADEPT) work?

Answer 15

• Specialised cancer targeting monoclonal antibodies with an enzyme attachment are administered to the patient
• These anitbody-enzyme complexes circulate the body until they bind to receptors on target cancer cells
• A harmless prodrug is then administered to the patient
• The enzyme attached to the cancer cell activates the prodrug, converting it into its cytotoxic form right on the cancer cell
• Since the prodrug is activated at the cancer cell it kills the cancer cells and not surrounding tissue

Question 16

Under what conditions must liposomes be fabricated?

Answer 16

• 5-10 degrees above the chain melting transition temperature because they are fluid e in this state

Question 17

How are liposomes fabricated?
5 steps

Answer 17

1) Choose a lipid molecule that you want to create a bilayer from
2) Dissolve the lipid in an organic solvent
3) Evaporate the solvent, leaving a thin film of lipid
4) Hydrate the lipid film by adding an aqueous solution containing the drug, from this large Multilamellar vesicles (MLVs) varying in size will naturally form containing the drug solution
5) Subject the MLVs to sonication or extrusion to reduce the size of the vesicles to similar sized Small unilamellar vesicles (SUVs)