Title

Ph Driven Precipitation Of Quisinostat Onto Pla-Peg Nanoparticles Enables Treatment Of Intracranial Glioblastoma

Department

neurobiology

Document Type

Article

Abstract

Histone deacetylases (HDACs) are known to be key enzymes in cancer development and progression through their modulation of chromatin structure and the expression and post-translational modification of numerous proteins. Aggressive dedifferentiated tumors, like glioblastoma, frequently overexpress HDACs, while HDAC inhibition can lead to cell cycle arrest, promote cellular differentiation and induce apoptosis. Although multiple HDAC inhibitors, such as quisinostat, are of interest in oncology due to their potent in vitro efficacy, their failure in the clinic as monotherapies against solid tumors has been attributed to poor delivery. Thus, we were motivated to develop quisinostat loaded poly(D,L-lactide)-b-methoxy poly(ethylene glycol) nanoparticles (NPs) to test their ability to treat orthotopic glioblastoma. In developing our NP formulation, we identified a novel, pH-driven approach for achieving over 9% (w/w) quisinostat loading. We show quisinostat-loaded NPs maintain drug potency in vitro and effectively slow tumor growth in vivo, leading to a prolonged survival compared to control mice.

Publication Date

6-1-2018

Publication Title

Colloids and Surfaces B: Biointerfaces

ISSN

09277765

Volume

166

First Page

37

Last Page

44

Digital Object Identifier (DOI)

10.1016/j.colsurfb.2018.02.048

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