14: Protein Formulation and Delivery Flashcards

1
Q

polypeptides with ____ amino acids are called proteins

A

> 40

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2
Q

what determines the function of a protein

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

4

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3
Q

where can you find out more about protein drugs

A

drugbank

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4
Q

classes of protein pharmaceuticals

A

vaccines
peptides
blood products
recombinant therapeutic proteins

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5
Q

which of the following is not a therapeutic protein

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

4

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6
Q

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

A

F- weak noncovalent forces

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7
Q

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

A

F- weak noncovalent forces

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8
Q

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
A

2

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9
Q

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

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

oxidation (covalent change)

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10
Q

list some covalent problems for protein drugs in vitro

A

deamination
oxidation
disulfide exchange
proteolysis

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11
Q

what method of storage is best for long term storage

A

freeze drying

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12
Q

what is a problem with freezing proteins

A

freeze/ thawing process can denature proteins

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13
Q

why do low temps prolong storage times

A

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

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14
Q

what is the best packaging for proteins

A

smooth glass walls to reduce adsorption or precipitation

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15
Q

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
A

3

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16
Q

how to avoid light oxidation

A

dark, opaque walled containers

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17
Q

what do polyols do

A

help protein drug solubilize

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18
Q

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

A

Tt

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19
Q

how to deal with protein stability problems by changing the formulation

A
modify protein sequency
PEGylation
proteinylation
microsphere/ nanosphere encapsulation
formulating with permeabilizers
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20
Q

what is site directed mutagenesis

A

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

21
Q

what are some benefits of PEGylation

A

decreases immunogenicity and depot loss at injection sites

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

22
Q

attachment of additional or secondary proteins for invivo protection describes

A

proteinylation

23
Q

what is encapsulation

A

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

24
Q

what are the 2 types of microspheres

A

nonbiodegradable

biodegradable

25
Q

nonbiodegradable micropheres include

A

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

26
Q

what type of microspheres are preferred

A

biodegradable

27
Q

what kind of microsphere release is good for burst release

A

hydrophilic

28
Q

what kind of microsphere release is good for sustained release

A

hydrophobic

29
Q

what is a problem with hydrophobic microsphere release

A

tends to denature proteins

30
Q

what kind of release is a hybrid microsphere release good for

A

sustained release + keeps proteins active

31
Q

3 subgroups of polymer degradation

A

hydrolysis
enzymative degradation
combination

32
Q

what are nanospheres

A

lipid micelles for protein delicery

33
Q

what are some examples of nanoparticles for protein delivery

A

exosomes
niosomes
solid lipid nanoparticles
polymersomes

34
Q

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
A

2

35
Q

what is the hydrophobic and hydrophilic portions of polymersomes

A

peptide core =hydrophobic

peg shell = hydrophilic

36
Q

list permeabilizer adjuvant examples

A

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

37
Q

what route of delivery allows for most protein to be absorbed

A

parenteral IV

38
Q

what are some problems with IV protein

A

overdosing, necrosis, local tissue reactions, hypersensitivity

39
Q

what is exubera

A

dry powder insulin

40
Q

how was oralin absorbed

A

insulin absorbed through thin tissue layers in mouth and throat

41
Q

what kind of system are pH sensitive microspheres dependent on

A

gel/ micrcosphere system with polymethacrylic acid + PEG

42
Q

how do pH sensitive microspheres work

A

pores shrink in stomach with low pH

pores open in small intestine with neutral pH = releases proteins

43
Q

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

A

complexation

44
Q

what are GIT patches

A

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

45
Q

what protects drugs from proteolytic degradation in a mucoadhesive patch

A

ethylcellulose film

46
Q

what are the 4 layers of a mucoadhesive patch

A

ehtylcellulose backing
drug container
mucoadhesive glu
pH surface layer

47
Q

how does the GIT patches know where to stick

A

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

48
Q

transdermal patches are basically a less painful form of _____ delivery

A

parenteral

49
Q

what is micromachining

A

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