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HDAC Inhibitor Conjugated Polymeric Prodrug Micelles for Doxorubicin Delivery.


ABSTRACT: Amphiphilic diblock copolymers bearing histone deacetylase inhibitors (HDACi) (4-phenyl butyric acid and valproic acid) were synthesized by the ring-opening polymerization of ?-4-phenylbutyrate-?-caprolactone (PBACL), ?-valproate-?-caprolactone (VPACL), and ?-caprolactone (CL) from a poly(ethylene glycol) macroinitiator (PEG). 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.

SUBMITTER: Senevirathne SA 

PROVIDER: S-EPMC5473365 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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HDAC Inhibitor Conjugated Polymeric Prodrug Micelles for Doxorubicin Delivery.

Senevirathne Suchithra A SA   Washington Katherine E KE   Miller Jason B JB   Biewer Michael C MC   Oupicky David D   Siegwart Daniel J DJ   Stefan Mihaela C MC  

Journal of materials chemistry. B 20170220 11


Amphiphilic diblock copolymers bearing histone deacetylase inhibitors (HDACi) (4-phenyl butyric acid and valproic acid) were synthesized by the ring-opening polymerization of γ-4-phenylbutyrate-ε-caprolactone (PBACL), γ-valproate-ε-caprolactone (VPACL), and ε-caprolactone (CL) from a poly(ethylene glycol) macroinitiator (PEG). These amphiphilic diblock copolymers self-assembled into stable pro-drug micelles and demonstrated excellent biocompatibility. High loading of doxorubicin (DOX) up to 5.1  ...[more]

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