Advanced delivery system

Question 1

How can we fix ADME properties

Answer 1

Decrease metabolism
Stabilize negative charge
Increase tissue distribution

Question 2

Describe RNA nanoparticle drugs

Answer 2

Use same basic technology as Doxil (liposome)
From lipid nanoparticle rather than a liposome

Question 3

Describe nucleic acid formulations

Answer 3

Cationic lipids used to condense nucleic acids and shield negative charge
Cholesterol and helper lipids used to maintain membrane stability
PEG-lipid shields from antibodies and cell adhesion in body
mRNA vaccines used very similar formulation

Question 4

Describe CRISPr formulations

Answer 4

lipid nanoparticles - Targets PCSK9 gene in liver
LNP
body doesn’t like particles - go to liver, spleen, lungs and kidney

Question 5

What is the biggest limitation to CRISPr technology

Answer 5

We can’t get it to where we want in the body
Formulations key to fully unlock technology if it ever happens.

Question 6

Describe the mechanism of VERVE-101 action

Answer 6

High blood LDL-C -> clogged arteries resulting in ASCVD
mRNA translated into base editing protein - turns off PCSK9 gene and lowers blood LDL-C

Question 7

Describe transdermal drug delivery

Answer 7

0 order release
Improved patient compliance
Reduces abuse potential of opioids

Question 8

What are the disadvantages of transdermal drug delivery

Answer 8

Only small molecule drugs
Must be hydrophobic
Typically need to be very potent

Question 9

What is the logP of transdermal drug delivery

Answer 9

between 1 and 3
less than 1 mg per day
MP < 200 degrees C

Question 10

What is the release rate of transdermal patches

Answer 10

Consistent levels rarely seen in in vivo
Drug conc. fluctuate and individual variability observed

Question 11

Describe implanted drug delivery

Answer 11

Can utilize 0 order release
Must have high potency
Can improve patient compliance

Question 12

Describe implant device release

Answer 12

Relatively consistent release (30-70 micrograms/day)
- decrease drug conc. over time
- Slight variation in conc. occur over time

Question 13

Describe transnasal drug delivery

Answer 13

Local delivery to sinus cavity
Bypass first-pass metabolism to get to circulation
Rapid onset of action
Possibility for bypassing blood-brain barrier for CNS drugs

Question 14

What are the disadvantages to intranasal drug delivery

Answer 14

Cleared more rapidly
Nasal cavity is sensitive
Mucus prevents absorption of drugs into blood
Limited volumes administered (100-150 microL)