Frequently Asked Questions about PharmaIN PGC Platform
A: Loading is based on weight/weight with API/PGC. It depends on the affinity to PGC. Typical loading is 2-10% loading and we recommend initial testing at 5% loading.
Q: How does the API bind to PGC?
A: Non-covalent interaction, mainly hydrophobic interaction.
Q: How can I know if my API will bind to PGC?
A: Peptide will likely bind if the recommended criteria are met. Testing is only way to find out with certainty.
Q: Can the binding and releasing mechanisms be changed?
A: Yes, by custom PGC engineering.
Q: When you say you custom PGC engineering, what does this mean?
A: By changing the binding mode using a different binding moiety.
Q: Can PGC work with a very small peptide (< 15 amino acids)?
A: Unfortunately the chances are low, because the binding affinity relies on multiple binding moieties on the API. However, we can offer a peptide engineering option.
Q: Would a monoclonal antibody work with PGC?
A: Not likely because it would exceed our size criteria.
Q: I have a peptide with a covalently attached cholesterol tail, would this work with PGC?
A: Yes, a peptide with fatty acid/hydrophobic moiety will likely work.
Q: How heavy a load can PGC take?
A: Up to 20% by weight, depending on API affinity.
Q: How is the API released?
A: PGC-API is in equilibrium with a small amount of free API and surroundings. As free API is eliminated, more will be released from PGC.
Q: How does the API affect the release rate?
A: Each API would have different degree of binding. High affinity API will have a slow release rate, low affinity API will have a fast release rate.
Q: Can I estimate the half-life extension of my API with PGC?
A: No, this must be determined by experiment.
Q: Can the PK profile be changed?
A: Yes, by changing the loading %. The lower loading will extend the PK profile, and the higher loading will shorten the PK profile.
Q: Are the PEGs all the same size?
Q: Why 5kDa PEG?
A: Because once it is cleaved from PGC by enzymes, it is removed from circulation within minutes. Smaller PEG won’t provide shielding of API. Larger PEG won’t be eliminated as fast.
Q: Please explain how the passive targeting works?
A: Because the size of PGC is 15-22nm and the leaky vasculature of solid tumor, infection, inflammation has porosity of the similar size.
Q: Could PGC work for a mucosal therapy?
A: It is possible, but not tested.
Q: What amount of depot effect would subcutaneous PGC give?
A: Often to support daily or up to weekly retention time after SC administration.
Q: How fast does PGC get eliminated from the body?
A: PGC half life is 20±5 hrs.
Q: How does PGC eliminated?
A: PGC degradation products are eliminated primarily through the kidney.
Q: Is the safety of PGC already proven?
A: PGC is proven to be non-toxic in dogs for at least 20x recommended dose, and we are entering clinical trials very soon.
Q: What buffers are compatible with PGC?
A: Avoid using Phosphate buffers for metal bridge carrier.
Q: Are there any incompatible formulation components when using PGC?
A: Do not use Detergents
Q: How do I formulate my peptide with PGC?
A: Contact PharmaIN