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Topic: Polymer-Prodrug Ester bond  (Read 295 times)

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Offline skh1996

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Polymer-Prodrug Ester bond
« on: March 16, 2020, 03:52:59 PM »
Hi ,
I have a polymer prodrug consisting of polymer attached to camptothecin via an ester bond. I am wanting to remove excess drug from the mixture to yield a pure sample. One of the protocols I have read mentions they used a dialysis method for this but used deionised water to do so  :o. Would this surely not cleave the ester bond?  Am I missing something vital in this?

Many Thanks

Offline Babcock_Hall

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Re: Polymer-Prodrug Ester bond
« Reply #1 on: March 16, 2020, 05:49:16 PM »
What things do you know that catalyze the hydrolysis of ester bonds?

Offline pgk

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Re: Polymer-Prodrug Ester bond
« Reply #2 on: March 18, 2020, 02:01:16 PM »
Please, do not confuse the liberation of the drug bonded with a prodrug carrier via ester hydrolysis in body fluids at a particular pH, with ester hydrolysis in neutral deionized water.
Besides, edible oils and butter are not hydrolyzed in boiling water during cooking; neither polyester-made boats are hydrolyzed at sea. 
« Last Edit: March 18, 2020, 02:52:19 PM by pgk »

Offline skh1996

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Re: Polymer-Prodrug Ester bond
« Reply #3 on: March 18, 2020, 04:43:03 PM »
Please, do not confuse the liberation of the drug bonded with a prodrug carrier via ester hydrolysis in body fluids at a particular pH, with ester hydrolysis in neutral deionized water.
Besides, edible oils and butter are not hydrolyzed in boiling water during cooking; neither polyester-made boats are hydrolyzed at sea. 

What things do you know that catalyze the hydrolysis of ester bonds?

Thank you both for your help, it is very much appreciated :)  ;
So as I understand ( ???), hydrolysis of an ester has mechanisms which can either be catalysed by base, or by acid.

And since deionised water is neutral, it would not be able to participate in either of these processes to attack the ester bond?

Therefore were I to conduct ultracentrifugal dialysis in water (or even water/ethanol mix) within a 60 minute time period followed by freeze drying, my prodrug ester bond in the compound should remain intact (?)

Offline hollytara

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Re: Polymer-Prodrug Ester bond
« Reply #4 on: March 19, 2020, 12:41:06 AM »
Yes, but it is always good to be certain.  Will you have enough material to take an IR before and after?  If there is any odd hydrolysis (maybe your pro-drug self-catalyzes its own hydrolysis?), you will see the carboxylic acid appear through O-H and C=O stretch changes.

Offline Babcock_Hall

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Re: Polymer-Prodrug Ester bond
« Reply #5 on: March 19, 2020, 10:01:26 AM »
It is not beyond the realm of possibility that an esterase enzyme could present as a contaminant.  I don't think it is terribly likely, but contaminating proteases and nucleases have been known to cause problems in other applications.

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