Synthesis of pro-drugs for carboxylic acid containing drugs for polyurethane drug delivery materials
Adamson, Nathan Joseph
Tonks, Neal E
Chemistry and Biochemistry
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Polyurethanes are being developed for drug delivery purposes by incorporating a pro-drug diol into the polyurethane matrix to produce a material that will slowly release the drug under physiological conditions. Two novel methods have been developed for pro-drug synthesis: 1. acylation of anhydride intermediate and 2. via Mitsunobu esterification The pro-drug is produced via the esterification with (2,2-dimethyl-1,3-dioxolan-4-yl)methanol (solketal) followed by cleavage of the ketal to reveal a diol. The diol allows the pro-drug to be covalently incorporated into the polyurethane backbone produced using an aliphatic diisocyanate and a biologically derived polyol. The ester linkage to the polyurethane backbone is easily cleaved under physiological conditions for drug releasing purposes, and it is possible to detect drug release using HPLC after incubating the polyurethane in PBS media at 37°C.