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dc.contributor.authorChowdhury, Ananda
dc.contributor.authorMarin, Alexander
dc.contributor.authorWeber, David J.
dc.contributor.authorAndrianov, Alexander K.
dc.date.accessioned2021-11-18T18:42:29Z
dc.date.available2021-11-18T18:42:29Z
dc.date.issued2021-11-02
dc.identifier.urihttp://hdl.handle.net/10713/17153
dc.description.abstractSelf-assembly of ionically charged small molecule drugs with water-soluble biodegradable polyelectrolytes into nano-scale complexes can potentially offer a novel and attractive approach to improving drug solubility and prolonging its half-life. Nanoassemblies of quisinostat with water-soluble PEGylated anionic polyphosphazene were prepared by gradient-driven escape of solvent resulting in the reduction of solvent quality for a small molecule drug. A study of binding, analysis of composition, stability, and release profiles was conducted using asymmetric flow field flow fractionation (AF4) and dynamic light scattering (DLS) spectroscopy. Potency assays were performed with WM115 human melanoma and A549 human lung cancer cell lines. The resulting nano-complexes contained up to 100 drug molecules per macromolecular chain and displayed excellent water-solubility and improved hemocompatibility when compared to co-solvent-based drug formulations. Quisinostat release time (complex dissociation) at near physiological conditions in vitro varied from 5 to 14 days depending on initial drug loading. Multimeric complexes displayed dose-dependent potency in cell-based assays and the results were analyzed as a function of complex concentration, as well as total content of drug in the system. The proposed self-assembly process may present a simple alternative to more sophisticated delivery modalities, namely chemically conjugated prodrug systems and nanoencapsulation-based formulations.en_US
dc.description.sponsorshipNational Science Foundationen_US
dc.description.urihttps://doi.org/10.3390/pharmaceutics13111834en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofPharmaceuticsen_US
dc.subjectHistone deacetylase inhibitorsen_US
dc.subjectPEGylationen_US
dc.subjectPolyphosphazenesen_US
dc.subjectQuisinostaten_US
dc.subjectSlow-releaseen_US
dc.titleNano-assembly of quisinostat and biodegradable macromolecular carrier results in supramolecular complexes with slow-release capabilitiesen_US
dc.typeArticleen_US
dc.identifier.doi10.3390/pharmaceutics13111834
dc.source.volume13
dc.source.issue11


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