Simvastatin was polymerized into copolymers to better control drug loading and release for therapeutic delivery. When using the conventional stannous octoate catalyst in ring-opening polymerization (ROP), reaction temperatures ≥ 200 °C were required, which promoted uncontrollable and undesirable side reactions. Triazabicyclodecene (TBD), a highly reactive guanidine base organocatalyst, was used as an alternative to polymerize simvastatin. Polymerization was achieved at 150 °C using 5 kDa methyl-terminated poly(ethylene glycol) (mPEG) as the initiator. ROP reactions with 2 kDa or 550 Da mPEG initiators were also successful using TBD at 150 °C instead of stannous octoate, which required a higher reaction temperature. Biodegradability of the poly(simvastatin) copolymer in phosphate-buffered saline was also improved, losing twice as much mass than the copolymer synthesized via stannous octoate. The three copolymers exhibited modified rates of simvastatin release, demonstrating tunablity for drug delivery applications.
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This research was funded by the National Institutes of Health (AR060964-02S1 and EB017902).
Asafo-Adjei, Theodora A.; Dziubla, Thomas D.; and Puleo, David A., "Tuning Properties of Poly(ethylene glycol)-block-poly(simvastatin) Copolymers Synthesized via Triazabicyclodecene" (2017). Biomedical Engineering Faculty Publications. 37.