Lecture 23

Question 1

nano-particulate drug carriers

Answer 1

micelles/polymeric micelles
liposomes
protein nanoparticles

Question 2

micelles

Answer 2

surfactant molecules aggregate in aqueous solution to form micelles at certain concentration and temperature

Question 3

surfactant in micelles

Answer 3

hydrophilic polar head (anionic, cationic, zwitterionic, non-ionic)
non-polar long chain tail

Question 4

block co-polymers in micelles

Answer 4

hydrophilic polymer blocker (PEG)
hydrophobic polymer blocker (PLA)

Question 5

taxol (bristol-myers squibb)

Answer 5

paclitaxel (6mg) and cremophor el (527mg, non-ionic surfactant) in 1mL of 49.7% dehyrdate alcohol
indications
- first line and subsequent therapy for treatment of advanced carcinoma of the ovary (together cisplatin)
- adjuvant treatment of node-positive breast cancer
- first line treatment of non-small cell lung cancer
- second line treatment of AIDS-related Kaposi’s sarcoma

Question 6

paclitaxel

Answer 6

part of taxol
bark of a pacific yew tree
prepared via semi-synthetic process from Taxus baccata
prevents depolymerization of microtubules
highly lipophilic, insoluble in water

Question 7

liposomes

Answer 7

vesicular structures based on one or more lipid bilayers
made up of phospholipids and cholesterol

Question 8

phospholipids

Answer 8

can be natural or synthetic
hydrophilic polar head group and nonpolar hydrophobic group
spontaneously arrange to form thermodynamically most stable bilayer structures, where hydrophilic head groups protrude outside into the aqueous environment and hydrophobic tails orient inward, away from water
flat bilayers self-close into concentric compartments around a central aqueous phase to form liposomes

Question 9

doxil (doxorubicin in liposome)

Answer 9

composed of doxorubicin HCl and pegylated liposomes
indications - ovarian cancer, AIDS-related Kaposi’s sarcoma, multiple myeloma (brotezomib)
side effects - hand foot syndrome

Question 10

albumin

Answer 10

protein nanoparticle
natural carrier of hydrophobic molecules (vitamins, hormones, other plasma constituents) in the blood
reversibly binds to hydrophobic substances
facilitates endothelial transcytosis of albumin-bound drug (binds to gp60 receptor, caveolae-mediated transcytosis)
preferential intratumoral accumulation of paclitaxel via binding to SPARC

Question 11

SPARC

Answer 11

secreted protein acidic and rich in cysteine
an extracellular matrix glycoprotein overexpressed in a variety of cancers

Question 12

abraxane

Answer 12

paclitaxel protein-bound particles for injectable suspensions
indicated - treatment of metastatic breast cancer
100 mg of paclitaxel and 900 mg of human albumin
free of solvent or surfactant
avoids complications related to surfactants (like with cremophor EL)
maximum tolerated dose: 50% higher than typical dose used with taxol