Nanomedicine and EPR

Question 1

What are liposomes made of

Answer 1

Hydrophilic head and hydrophobic tail
Amphipathic molecules and can self-assemble
Can also have cholesterol contained

Question 2

What does cholesterol do to liposomes

Answer 2

reduces permeability so increases drug retention in liposome

Question 3

What is passive and active loading of liposomes

Answer 3

Passive- Mix drug and lipids, lipids form into liposome with drug contained

Active (remote)- Preformed liposome with a pH / ionic gradient
Loading driven by pH/ionic gradient
Drug aggregate forms inside as travels with gradient into liposome

Question 4

Why do we encapsulate drugs in liposomes?

Answer 4

alter pharmacokinetics and distribution of drug
Function as drug reservoir (for sustained release)

Question 5

How can liposomes work for cancer

Answer 5

Liposomes can interact with blood opsonins (antibodies that mark foreign cells for phagocytosis)
Opsonised liposomes ender mononuclear phagocytic system (MPS)
Causes a build up of drug-containing liposomes at these sites
Mimics slow transfusion of drugs

Question 6

When MPS deposition isn’t useful for cancer what can we do:

Answer 6

Opsonisation must be avoided
Stability, clearance and tissue distribution is now important
Can used surface modifications to create hydrophilic surfaces that repel opsonins and maintain liposome in circulation
Allows liposomes to accumulate at pathogenic sites as EPR effect

Question 7

What is the EPR effect

Answer 7

Enhanced permeability and retention effect
Drug accumulates at site of action eg: tumours

Question 8

What is different between getting a liposome to aggregate at a site of action vs albumin

Answer 8

Albumin doesnt need PEGylation (modifications) to avoid markers

Question 9

What are solid lipid nanoparticles and why are they good

Answer 9

Lipid core matrix
High drug encapsulation efficiency

Usually increases oral bioavailability by 2-25x!!

Question 10

Why are mechanisms like self-nano-emulsifying drug delivery used

Answer 10

used for delivery of nucleic acids ETC to improve stability and delivery

Question 11

Explain clearance of nanoparticles

Answer 11

renal = urine
hepatic= bile= stools

Mononuclear phagocytic system- MPS- takes up large particles can retain for months / years
Surface coatings (PEG dextrans etc) can help avoid opsonisation and MPS uptake

If too large for renal clearance and avoiding MPS, hepatic clearance will occur

Question 12

What is EPR

Answer 12

Enhanced permeability and retention

tumours etc epithelial cells of blood vessels are distorted so liposome can go into tumour easily
Also retention as lymphatic system is broken and waste cant be removed