14: Protein Formulation and Delivery

Question 1

polypeptides with ____ amino acids are called proteins

Answer 1

> 40

Question 2

what determines the function of a protein

1. covalent interactions
2. primary structure
3. affinity to binding proteins
4. noncovalent 3D structure

Answer 2

4

Question 3

where can you find out more about protein drugs

Answer 3

drugbank

Question 4

classes of protein pharmaceuticals

Answer 4

vaccines
peptides
blood products
recombinant therapeutic proteins

Question 5

which of the following is not a therapeutic protein

1. vaccines
2. factor X
3. interferon beta
4. secretagogues

Answer 5

4

Question 6

T or F: proteins are very large but are stable as they are held together by strong covalent forces

Answer 6

F- weak noncovalent forces

Question 7

T or F: proteins are very large but are stable as they are held together by strong covalent forces

Answer 7

F- weak noncovalent forces

Question 8

which of the following is a problem with proteins in vivo

1. elimination by dendritic cells
2. small proteins filtered out by kidneys very fast
3. tends to stay in the body for too long
4. can’t be injected SQ

Answer 8

2

Question 9

which of the following is not a noncovalent in vitro problem for protein drugs

1. denaturation
2. oxidation
3. aggregation
4. precipitation

Answer 9

oxidation (covalent change)

Question 10

list some covalent problems for protein drugs in vitro

Answer 10

deamination
oxidation
disulfide exchange
proteolysis

Question 11

what method of storage is best for long term storage

Answer 11

freeze drying

Question 12

what is a problem with freezing proteins

Answer 12

freeze/ thawing process can denature proteins

Question 13

why do low temps prolong storage times

Answer 13

reduces microbial growth and metabolism
reduces thermal or spontaneous denaturation
reduces adsorption

Question 14

what is the best packaging for proteins

Answer 14

smooth glass walls to reduce adsorption or precipitation

Question 15

which of the following is true

1. protein drugs should be packed in polystyrene or containers with silanyl or plasticizer coatings to prevent adsorption
2. stabilizing salts or ions actually cause proteins to aggregate
3. argon atmosphere reduces protein drug oxidation
4. freeze drying requires sugars or dextran to displace water/ reduce microbe growth

Answer 15

3

Question 16

how to avoid light oxidation

Answer 16

dark, opaque walled containers

Question 17

what do polyols do

Answer 17

help protein drug solubilize

Question 18

T or F: in the process of freeze drying, some proteins will become deactivated as water is removed

Answer 18

Tt

Question 19

how to deal with protein stability problems by changing the formulation

Answer 19

modify protein sequency
PEGylation
proteinylation
microsphere/ nanosphere encapsulation
formulating with permeabilizers

Question 20

what is site directed mutagenesis

Answer 20

protein sequence modification at specific sites to increase stability
ex- more disulfide bonds with cysteines = higher Tm, substituting AA to reduce chance of oxidation

Question 21

what are some benefits of PEGylation

Answer 21

decreases immunogenicity and depot loss at injection sites

increases in vivo half life, protease resistance, and solubility and stability

Question 22

attachment of additional or secondary proteins for invivo protection describes

Answer 22

proteinylation

Question 23

what is encapsulation

Answer 23

encapsullating protein or peptide drugs in small porous particles for protection from insults + for sustained release

Question 24

what are the 2 types of microspheres

Answer 24

nonbiodegradable

biodegradable

Question 25

nonbiodegradable micropheres include

Answer 25

ceramic particles – polyethylene co-vinyl acetate – polymethacrylic acid/PEG

Question 26

what type of microspheres are preferred

Answer 26

biodegradable

Question 27

what kind of microsphere release is good for burst release

Answer 27

hydrophilic

Question 28

what kind of microsphere release is good for sustained release

Answer 28

hydrophobic

Question 29

what is a problem with hydrophobic microsphere release

Answer 29

tends to denature proteins

Question 30

what kind of release is a hybrid microsphere release good for

Answer 30

sustained release + keeps proteins active

Question 31

3 subgroups of polymer degradation

Answer 31

hydrolysis enzymative degradation combination

Question 32

what are nanospheres

Answer 32

lipid micelles for protein delicery

Question 33

what are some examples of nanoparticles for protein delivery

Answer 33

exosomes niosomes solid lipid nanoparticles polymersomes

Question 34

which of the following are true 1. exosomes are 10-20nm 2. niosomes are nonionic surfactant vesicles made from surfactants and cholesterol 3. solid lipid nanoparticles are composed of a liquid lipid nucleus 4. polymersomes are lipophilic

Answer 34

2

Question 35

what is the hydrophobic and hydrophilic portions of polymersomes

Answer 35

peptide core =hydrophobic | peg shell = hydrophilic

Question 36

list permeabilizer adjuvant examples

Answer 36

salicylates fatty acids metal chelators anything that is known to punch holes into the intestine or lumen

Question 37

what route of delivery allows for most protein to be absorbed

Answer 37

parenteral IV

Question 38

what are some problems with IV protein

Answer 38

overdosing, necrosis, local tissue reactions, hypersensitivity

Question 39

what is exubera

Answer 39

dry powder insulin

Question 40

how was oralin absorbed

Answer 40

insulin absorbed through thin tissue layers in mouth and throat

Question 41

what kind of system are pH sensitive microspheres dependent on

Answer 41

gel/ micrcosphere system with polymethacrylic acid + PEG

Question 42

how do pH sensitive microspheres work

Answer 42

pores shrink in stomach with low pH | pores open in small intestine with neutral pH = releases proteins

Question 43

the process of shrinking and swelling of pH sensitive microspheres is called

Answer 43

complexation

Question 44

what are GIT patches

Answer 44

a form of delivery where you swallow the capsule, it goes into the intestines and adheres, releasing the drug slowly = mucoadhesive patch

Question 45

what protects drugs from proteolytic degradation in a mucoadhesive patch

Answer 45

ethylcellulose film

Question 46

what are the 4 layers of a mucoadhesive patch

Answer 46

ehtylcellulose backing drug container mucoadhesive glu pH surface layer

Question 47

how does the GIT patches know where to stick

Answer 47

has a pH sensitive surface layer that determines the adhesive site in the GIT

Question 48

transdermal patches are basically a less painful form of _____ delivery

Answer 48

parenteral

Question 49

what is micromachining

Answer 49

use of photolithography of electron beams to carve holes into metal plates which are placed over small boxes containing islet cells- insulin can leak out but antibodies too big to get in