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

doi:10.1039/c6tb03038f

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 journal › Article › peer-review

16 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 language	English (US)
Pages (from-to)	2106-2114
Number of pages	9
Journal	Journal of Materials Chemistry B
Volume	5
Issue number	11
DOIs	https://doi.org/10.1039/c6tb03038f
State	Published - 2017

ASJC Scopus subject areas

Chemistry(all)
Biomedical Engineering
Materials Science(all)

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10.1039/c6tb03038f

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title = "HDAC inhibitor conjugated polymeric prodrug micelles for doxorubicin delivery",

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.",

author = "Senevirathne, {Suchithra A.} and Washington, {Katherine E.} and Miller, {Jason B.} and Biewer, {Michael C.} and David Oupicky and Siegwart, {Daniel J.} and Stefan, {Mihaela C.}",

note = "Funding Information: M. C. S. and D. O. acknowledge grant support from NIH (1R21EB019175-01A1). M. C. S. also acknowledges grant support from Welch Foundation (AT-1740) and NSF (DMR-1505950). D. J. S. acknowledges grant support from the Cancer Prevention and Research Institute of Texas (CPRIT) (R1212) and the Welch Foundation (I-1855). J. B. M. acknowledges fellowship support from CPRIT (RP140110). Publisher Copyright: {\textcopyright} The Royal Society of Chemistry.",

year = "2017",

doi = "10.1039/c6tb03038f",

language = "English (US)",

volume = "5",

pages = "2106--2114",

journal = "Journal of Materials Chemistry B",

issn = "2050-7518",

publisher = "Royal Society of Chemistry",

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TY - JOUR

T1 - HDAC inhibitor conjugated polymeric prodrug micelles for doxorubicin delivery

AU - Senevirathne, Suchithra A.

AU - Washington, Katherine E.

AU - Miller, Jason B.

AU - Biewer, Michael C.

AU - Oupicky, David

AU - Siegwart, Daniel J.

AU - Stefan, Mihaela C.

N1 - Funding Information: M. C. S. and D. O. acknowledge grant support from NIH (1R21EB019175-01A1). M. C. S. also acknowledges grant support from Welch Foundation (AT-1740) and NSF (DMR-1505950). D. J. S. acknowledges grant support from the Cancer Prevention and Research Institute of Texas (CPRIT) (R1212) and the Welch Foundation (I-1855). J. B. M. acknowledges fellowship support from CPRIT (RP140110). Publisher Copyright: © The Royal Society of Chemistry.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

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DO - 10.1039/c6tb03038f

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AN - SCOPUS:85015199670

SN - 2050-7518

VL - 5

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EP - 2114

JO - Journal of Materials Chemistry B

JF - Journal of Materials Chemistry B

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ER -

HDAC inhibitor conjugated polymeric prodrug micelles for doxorubicin delivery

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