Polymers Flashcards
What is a polymer drug conjugate?
chemically conjugate between a polymer and a drug
What is a Targeting moiety ?
target specific receptors/tissue. Can attach that to one of the chemical functions on the polymer chain.
What is a NEUTRAL polymer example?
Neutral: PEG, hydroxypropylmethacrylamide (HPMA), dextran
What is a CATIONIC polymer example?
Poy(lysine)
Cationic polymers are used to deliver nucleic acids such as plasma and DNA
What is a ANIONIC polymer example?
Poly(aspartic acid), Poly(glutamic acid)
What are the 2 main reasons to why nanomedicine can disappear from the blood circulation?
- It’s being degraded and eliminated by the kidney
2. Left the blood compartment and is accumulating in the tissue compartment
What is the EPR effect?
E = enhanced P = permeation “badly made blood vessels” R = retention “poor waste collection”
EPR: The basis to why nanomedicine is used for Tumours. Tumours develop quickly so they form new blood vessels, they will have larger pores so then nano-medicines, if the size is right, will be able to leave the blood circulation and be able to accumulate outside environment of the tumours. Once they are close to the tumour cells, lymphatic drainage – doesn’t work that well in tumours. When the nanomedicine gets to close to the tumour, it can stay very long there.
What is the main elimination route for polymer conjugates?
As polymer conjugates are water soluble, main elimination is through renal filtration.
What is the ideal size for a nanomedicine?
Ideal size for a nanomedicine is 60-100nm
What size will cause the polymer to be eliminated by the kisneys?
Glomerular filtration (limit 30-50 kDa) - Anything below 30-50, there is an increased chance the polymer will be eliminated by the kidney
What is the role of the MPS?
M = Mononuclear P = phagocyte S = system
Removal by the body’s defences (MPS) – Body can recognize it as something foreign so will be removed by phagocytes. More likely for large, hydrophobic or charged nanoparticles.
What size do you need to aim before to avoid accumulation in healthy tissue?
2-6 nm – minimum size (Need to target sizes above this to avoid accumulation in healthy tissues, large enough)
What is the mechanism of action of polymer-drug conjugates?
Once in tumour environment:
Take them up by pinocytosis (the ingestion of liquid into a cell by the budding of small vesicles from the cell membrane). – so take up anything in the aqueous environment.
Polymer drug conjugate will end up in an endosome which gets converted into a lisosome, and is enzymatically active. If they are degraded, then it can be released into the cytoplasm of the cell and exert its anticancer activity.
How does Polymer flexibility and morphology and orientation impact accumulation/elimination?
• Improved accumulation for rigid, tubular polymer chains
What are the different types of linkers?
- Non-biodegradable linkers - Should be avoided – as drug will be attached to polymer forever and never release the drug.
- Environment-sensitive linkers - pH-sensitive: esters and hydrazones – will tend to be degraded at acidic Ph. The outside environment around the tumor is slightly acidic in comparison to health tissues. pH can decrease to 5.5.-7.6. Risk that some of the drug will be released outside of the tumour.
• Sensitive to intracellular enzymatic degradation – to increase drug release
o Gly-Phe-Leu-Gly Ala–Leu-Ala-Leu (2 specific sequences of amino acids that the enzymes inside the liposomes will recognize
