I have tried synthesizing PEG-PLGA diblock copolymer using traditional EDC/NHS reaction. The problem here is the yield of the final product. It was around 20%. What could be the reason for this? Kindly suggest how to overcome this problem.
P.S.: I have used PLGA-COOH and mPEG-NH2 for the reaction. activated PLGA was precipitated with ice-cold ether and PEG-PLGA was precipitated with ice-cold methanol.
Your problem is quite different.: since the polyester is highly unstable towards hydrolysis and amino lysis the yield must be low with an carbodiimid !
Thus, I recommend simply to mix both polymers and some base, eg triethylamine, to deprotonate the amino end group and keep it without solvent at elevated temperature .
then you must obtain statistically composed block copolymers in quantitative yield.
good luck
Dear John,
Thanks for your suggestion.
I have followed EDC/NHS procedure after referring to many peer-reviewed publications which talked of PEG-PLGA synthesis. I will try with DIC/NHS this time. Can I use icecold methanol for precipitation?
Kindly suggest if this process can be performed as single-pot synthesis.
Thanks
Dear Prof. Ritter,
Thanks for your advice. New concept it is for me.
Kindly explain
How do I keep the polymers (solids) in solution state for reaction without addition of solvent? Doesn't it require activation of carboxylic group of PLGA in this process? What range of temperatures should I maintain for the reaction to occur?
Thanks in advance.
Dear Dr Kuranyi, ok, my suggestion depends on the MW of your polymers. If you use oligomers you may work in bulk around 100 -150 'C above the Tg values.
Alternatively, please try to use a commen dry solvent and mix both polymers plus traces of the tert. amine. Then it should work even around room temp.
All the best !!!
Dear Prof. Ritter,
We are using PLGA-COOH of mol.wt. of avg 31000 and PEG-NH2 of 5000 mol.wt. Was it the ring opening polymerization procedure you were suggesting?. Could that be followed for preformed polymers!!
Thanks
Dear Kiran,
Did you get a high conjugation between PLGA-COOH with amino-PEG? At present, I also used PLGA-COOH in solid state, we tried to conjugate with amino-protein, but the conjugation efficiency is still very low. Could you give me some suggestion to improve it? Thank you so much.
Hi Vishnu,
I am facing the same problem. I use PLGA-NHS with PEG-COOH in presence of DIEA in chloroform.
When i precipitate it, I get very small amount of precipitates. I have also tried centrifuging the solution, but I didn't get anything.
Kindly write if you were successful in getting a higher yield. Thanks
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