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

7 Citations (Scopus)

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 - Jan 1 2017

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Histone Deacetylase Inhibitors
Prodrugs
Valproic Acid
Micelles
Doxorubicin
Polyethylene glycols
Block copolymers
Bearings (structural)
Butyric acid
Butyric Acid
Ethylene Glycol
Ring opening polymerization
Biocompatibility
Polymerization
Pharmaceutical Preparations
Molecules
Acids
caprolactone
Therapeutics
Drug Liberation

ASJC Scopus subject areas

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

Cite this

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

HDAC inhibitor conjugated polymeric prodrug micelles for doxorubicin delivery. / Senevirathne, Suchithra A.; Washington, Katherine E.; Miller, Jason B.; Biewer, Michael C.; Oupicky, David; Siegwart, Daniel J.; Stefan, Mihaela C.

In: Journal of Materials Chemistry B, Vol. 5, No. 11, 01.01.2017, p. 2106-2114.

Research output: Contribution to journalArticle

Senevirathne, SA, Washington, KE, Miller, JB, Biewer, MC, Oupicky, D, Siegwart, DJ & Stefan, MC 2017, 'HDAC inhibitor conjugated polymeric prodrug micelles for doxorubicin delivery', Journal of Materials Chemistry B, vol. 5, no. 11, pp. 2106-2114. https://doi.org/10.1039/c6tb03038f
Senevirathne SA, Washington KE, Miller JB, Biewer MC, Oupicky D, Siegwart DJ et al. HDAC inhibitor conjugated polymeric prodrug micelles for doxorubicin delivery. Journal of Materials Chemistry B. 2017 Jan 1;5(11):2106-2114. https://doi.org/10.1039/c6tb03038f
Senevirathne, Suchithra A. ; Washington, Katherine E. ; Miller, Jason B. ; Biewer, Michael C. ; Oupicky, David ; Siegwart, Daniel J. ; Stefan, Mihaela C. / HDAC inhibitor conjugated polymeric prodrug micelles for doxorubicin delivery. In: Journal of Materials Chemistry B. 2017 ; Vol. 5, No. 11. pp. 2106-2114.
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