HDAC inhibitor conjugated polymeric prodrug micelles for doxorubicin delivery

Suchithra A. Senevirathne, Katherine E. Washington, Jason B. Miller, Michael C. Biewer, David Oupicky, Daniel J. Siegwart, Mihaela C. Stefan

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Amphiphilic diblock copolymers bearing histone deacetylase inhibitors (HDACis) (4-phenyl butyric acid and valproic acid) were synthesized by ring-opening polymerization of γ-4-phenylbutyrate-ε-caprolactone (PBACL), γ-valproate-ε-caprolactone (VPACL), and ε-caprolactone (CL) from a poly(ethylene glycol) (PEG) macroinitiator. These amphiphilic diblock copolymers self-assembled into stable pro-drug micelles and demonstrated excellent biocompatibility. High loading of doxorubicin (DOX) up to 5.1 wt% was achieved. Optimized micelles enabled sustained drug release in a concentration-dependent manner over time to expand the therapeutic window of cytotoxic small molecule drugs.

Original languageEnglish (US)
Pages (from-to)2106-2114
Number of pages9
JournalJournal of Materials Chemistry B
Volume5
Issue number11
DOIs
StatePublished - 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biomedical Engineering
  • Materials Science(all)

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    Senevirathne, S. A., Washington, K. E., Miller, J. B., Biewer, M. C., Oupicky, D., Siegwart, D. J., & Stefan, M. C. (2017). HDAC inhibitor conjugated polymeric prodrug micelles for doxorubicin delivery. Journal of Materials Chemistry B, 5(11), 2106-2114. https://doi.org/10.1039/c6tb03038f