14: Protein Formulation and Delivery Flashcards
polypeptides with ____ amino acids are called proteins
> 40
what determines the function of a protein
- covalent interactions
- primary structure
- affinity to binding proteins
- noncovalent 3D structure
4
where can you find out more about protein drugs
drugbank
classes of protein pharmaceuticals
vaccines
peptides
blood products
recombinant therapeutic proteins
which of the following is not a therapeutic protein
- vaccines
- factor X
- interferon beta
- secretagogues
4
T or F: proteins are very large but are stable as they are held together by strong covalent forces
F- weak noncovalent forces
T or F: proteins are very large but are stable as they are held together by strong covalent forces
F- weak noncovalent forces
which of the following is a problem with proteins in vivo
- elimination by dendritic cells
- small proteins filtered out by kidneys very fast
- tends to stay in the body for too long
- can’t be injected SQ
2
which of the following is not a noncovalent in vitro problem for protein drugs
- denaturation
- oxidation
- aggregation
- precipitation
oxidation (covalent change)
list some covalent problems for protein drugs in vitro
deamination
oxidation
disulfide exchange
proteolysis
what method of storage is best for long term storage
freeze drying
what is a problem with freezing proteins
freeze/ thawing process can denature proteins
why do low temps prolong storage times
reduces microbial growth and metabolism
reduces thermal or spontaneous denaturation
reduces adsorption
what is the best packaging for proteins
smooth glass walls to reduce adsorption or precipitation
which of the following is true
- protein drugs should be packed in polystyrene or containers with silanyl or plasticizer coatings to prevent adsorption
- stabilizing salts or ions actually cause proteins to aggregate
- argon atmosphere reduces protein drug oxidation
- freeze drying requires sugars or dextran to displace water/ reduce microbe growth
3
how to avoid light oxidation
dark, opaque walled containers
what do polyols do
help protein drug solubilize
T or F: in the process of freeze drying, some proteins will become deactivated as water is removed
Tt
how to deal with protein stability problems by changing the formulation
modify protein sequency PEGylation proteinylation microsphere/ nanosphere encapsulation formulating with permeabilizers
what is site directed mutagenesis
protein sequence modification at specific sites to increase stability
ex- more disulfide bonds with cysteines = higher Tm, substituting AA to reduce chance of oxidation
what are some benefits of PEGylation
decreases immunogenicity and depot loss at injection sites
increases in vivo half life, protease resistance, and solubility and stability
attachment of additional or secondary proteins for invivo protection describes
proteinylation
what is encapsulation
encapsullating protein or peptide drugs in small porous particles for protection from insults + for sustained release
what are the 2 types of microspheres
nonbiodegradable
biodegradable
nonbiodegradable micropheres include
ceramic particles
– polyethylene co-vinyl acetate
– polymethacrylic acid/PEG
what type of microspheres are preferred
biodegradable
what kind of microsphere release is good for burst release
hydrophilic
what kind of microsphere release is good for sustained release
hydrophobic
what is a problem with hydrophobic microsphere release
tends to denature proteins
what kind of release is a hybrid microsphere release good for
sustained release + keeps proteins active
3 subgroups of polymer degradation
hydrolysis
enzymative degradation
combination
what are nanospheres
lipid micelles for protein delicery
what are some examples of nanoparticles for protein delivery
exosomes
niosomes
solid lipid nanoparticles
polymersomes
which of the following are true
- exosomes are 10-20nm
- niosomes are nonionic surfactant vesicles made from surfactants and cholesterol
- solid lipid nanoparticles are composed of a liquid lipid nucleus
- polymersomes are lipophilic
2
what is the hydrophobic and hydrophilic portions of polymersomes
peptide core =hydrophobic
peg shell = hydrophilic
list permeabilizer adjuvant examples
salicylates
fatty acids
metal chelators
anything that is known to punch holes into the intestine or lumen
what route of delivery allows for most protein to be absorbed
parenteral IV
what are some problems with IV protein
overdosing, necrosis, local tissue reactions, hypersensitivity
what is exubera
dry powder insulin
how was oralin absorbed
insulin absorbed through thin tissue layers in mouth and throat
what kind of system are pH sensitive microspheres dependent on
gel/ micrcosphere system with polymethacrylic acid + PEG
how do pH sensitive microspheres work
pores shrink in stomach with low pH
pores open in small intestine with neutral pH = releases proteins
the process of shrinking and swelling of pH sensitive microspheres is called
complexation
what are GIT patches
a form of delivery where you swallow the capsule, it goes into the intestines and adheres, releasing the drug slowly = mucoadhesive patch
what protects drugs from proteolytic degradation in a mucoadhesive patch
ethylcellulose film
what are the 4 layers of a mucoadhesive patch
ehtylcellulose backing
drug container
mucoadhesive glu
pH surface layer
how does the GIT patches know where to stick
has a pH sensitive surface layer that determines the adhesive site in the GIT
transdermal patches are basically a less painful form of _____ delivery
parenteral
what is micromachining
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
