Last lecture

Question 1

Can CNS drug targeting be viewed as advanced drug delivery?

Answer 1

Yes; needs to pass BBB

Question 2

What are categories of nanoparticulate systems?

Answer 2

• nanocapsule (encapsulated drug, reservoir)

- nanospheres (drug-polymer matrix)

Question 3

T/F; Polymeric nanoparticles can only carry low MW substances.

Answer 3

False

• can deliver both low and high MW substances
• ex. genes, proteins

Question 4

What are the advantages of nanoparticles?

Answer 4

• increased bioavailability
• protection from degradation
• specific targets

Question 5

characteristics of tumor vasculature

Answer 5

• heterogeneous distribution
• larger in size
• high vascular density
• more permeable
• more leaky

Question 6

What factor allows retention of NP in solid tumors?

Answer 6

• high vasculature

- production of vascular mediators

Question 7

F

Answer 7

• bioavailability

- dose / AUC

Question 8

How can you actively target a tumor?

Answer 8

• ligand-receptor

- antibody-antigen

Question 9

How are NPs utilized in targeting cancer cells?

Answer 9

NP conjugated with tissue or cell-specific ligand

Question 10

examples of ligands

Answer 10

• lectins
• carbohydrates
• transferrin
• folate

Question 11

passive targeting

Answer 11

delivering drug at local site

Question 12

What are vectors?

Answer 12

gene carrier used in gene therapy

Question 13

Steps in gene therapy

Answer 13

• genetic material packaged in vector to be transferred
• vector enters cytoplasm
• gene from vector to nucleus
• gene integrated into cellular DNA (if need be)
• gene expressed

Question 14

What are the categories used in gene therapy?

Answer 14

• viral

- non-viral

Question 15

viral vectors

Answer 15

• part of viral genome replaced by therapeutic gene

- this gene taken up by target cells and expressed

Question 16

examples that viral vectors were used for

Answer 16

• retrovirus
• adenovirus
• adeno-associated virus
• herpes simplex virus (HSV)

Question 17

risks of viral vectors

Answer 17

• inflammation

- cellular / humoral immune response

Question 18

What are the components of a non-viral vector?

Answer 18

• therapeutic gene
• gene expression system
• gene delivery system

Question 19

plasmid-based vectors

Answer 19

non-viral

Question 20

size of plasmid DNA

Answer 20

• huge polyanion

- 100-200 nm

Question 21

Plasmid potency can be reduced by which factors?

Answer 21

• chemical instability
• enzymatic instability
• colloidal instability
• sequestered by immune system
• uptake / adsorption of non-target cells

Question 22

What are the most commonly used synthetic gene carrier?

Answer 22

• cationic polymers

- lipids

Question 23

What are advantages of using cationic polymers / lipids as a gene carrier?

Answer 23

they condense plasmids into small particles and protect them from degradation

Question 24

Lipid-based gene delivery

Answer 24

• low efficiency
• pH sensitive
• fusogenic at acidic pH
• facilitate release of plasmid in endosome

Question 25

Peptide-based gene delivery

Answer 25

linked macromolecules complexed into plasmids via electrostatic interaction

Question 26

Polymer-based gene delivery

Answer 26

• made to interact at a more cellular / protein level

- high specificity

Question 27

ideal features of gene delivery system

Answer 27

• reach appropriate cellular target
• penetrate into target cells
• gene integrate with cell’s DNA
• avoid destruction by body

Question 28

ex-vivo

Answer 28

• take cells out of body
• cells treated in lab
• cell inserted back in body

Question 29

in-vivo

Answer 29

• administration of vector in body

- low integration / efficacy