Nanomedicine

Question 1

Particle size

Answer 1

Directly or indirectly implicated in all aspects of drug delivery

Cellular uptake: endocytosis, phagocytosis

Flow in capillaries; embolization; extravasation

Adsorption of ligands: interactions with receptors

Question 2

Why nano?

Answer 2

Injectable intravenously

Unique biodistribution

With proper surface modification, nanoparticles can enter cells

Potential to modify biodistribution of a drug and increase drug delivery to target tissues via intravenous injection

Question 3

Nanoparticulate drug carriers

Answer 3

micelles/polymeric micelles

liposomes

protein nanoparticles

Question 4

Micelles

Answer 4

Hydrophilic moiety on hydrophilic head

Hydrophobic moiety on hydrophobic tail

As concentration of a surfactant increases above a critical concentration, the surfactant molecule self-associate into small aggregates called micelles

The micelles formed in water have the hydrophobic groups of the surfactant oriented toward the center of the micelle.

Question 5

Micelles (cont.)

Answer 5

Surfactant molecules aggregate in aqueous solution to form micelles at certain concentrations and temperatures

Question 6

Surfactant

Answer 6

hydrophilic polar head

anionic, cationic, zwitterionic, non-ionic

non-polar long chain tail

Question 7

Block copolymers

Answer 7

hydrophilic polymer block (PEG)

hydrophobic polymer block (PLA)

Question 8

High CMC

Answer 8

fast disintegration of micelles upton dilution

not desirable for synthetic drug delivery

Question 9

Polymeric micelles

Answer 9

for a micelle to be stable CMC must be low

Question 10

Taxol

Answer 10

Paclitaxel and Cremophor in 1 mL of 49.7% dehydrated alcohol

Question 11

Indications for Taxol

Answer 11

First-line for treatment of advanced carcinoma of the ovary

adjuvant treatment of node-positive breast cancer

first-line treatment of non-small cell lung cancer

second-line of AIDS

Question 12

Paclitaxel

Answer 12

bark of pacific yew tree

prepared via semi-synthetic process

prevents depolymerization of microtubules

highly lipophilic; insoluble in water

Question 13

Cremophor EL

Answer 13

non-ionic surfactant

Question 14

Precaution of cremophor

Answer 14

potential to leach out plasticizers from standard IV tubing
need special infusion sets

hypersensitivity reactions

premedicated with corticosteroids, antihistamines

Question 15

Polymeric micelles

Answer 15

amphiphilic block-polymer

PEG
PAA
PGA

Help solubilize hydrophobic drugs in water

less toxic than surfactants

Question 16

Liposomes

Answer 16

phospholipids: natural or synthetic

form thermodynamically most stable bilayer structures

cholesterol

Question 17

Cholesterol

Answer 17

immobilize the first few hydrocarbon groups of the phospholipid molecules. This makes the lipid bilayer less deformable and decrease permeability

Question 18

Stealth liposomes

Answer 18

Surface PEG prevents opsonization by:

shielding the surface charge

increasing surface hydrophilicity

enhancing repulsive interaction between liposomes and blood compartments

increase circulation time

Question 19

Abraxane

Answer 19

avoids complications related to surfactants

maximum tolerated dose: 50% higher than typical dose used with taxol