Nano-Assembly of Quisinostat and Biodegradable Macromolecular Carrier Results in Supramolecular Complexes with Slow-Release Capabilities

Self-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 PEGyla...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ananda Chowdhury, Alexander Marin, David J. Weber, Alexander K. Andrianov
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	quisinostat polyphosphazenes PEGylation slow-release histone deacetylase inhibitors Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/974a39141b1f4bfabaf287a1638f48df
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:974a39141b1f4bfabaf287a1638f48df
record_format	dspace
spelling	oai:doaj.org-article:974a39141b1f4bfabaf287a1638f48df2021-11-25T18:41:01ZNano-Assembly of Quisinostat and Biodegradable Macromolecular Carrier Results in Supramolecular Complexes with Slow-Release Capabilities10.3390/pharmaceutics131118341999-4923https://doaj.org/article/974a39141b1f4bfabaf287a1638f48df2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1834https://doaj.org/toc/1999-4923Self-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.Ananda ChowdhuryAlexander MarinDavid J. WeberAlexander K. AndrianovMDPI AGarticlequisinostatpolyphosphazenesPEGylationslow-releasehistone deacetylase inhibitorsPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1834, p 1834 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	quisinostat polyphosphazenes PEGylation slow-release histone deacetylase inhibitors Pharmacy and materia medica RS1-441
spellingShingle	quisinostat polyphosphazenes PEGylation slow-release histone deacetylase inhibitors Pharmacy and materia medica RS1-441 Ananda Chowdhury Alexander Marin David J. Weber Alexander K. Andrianov Nano-Assembly of Quisinostat and Biodegradable Macromolecular Carrier Results in Supramolecular Complexes with Slow-Release Capabilities
description	Self-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.
format	article
author	Ananda Chowdhury Alexander Marin David J. Weber Alexander K. Andrianov
author_facet	Ananda Chowdhury Alexander Marin David J. Weber Alexander K. Andrianov
author_sort	Ananda Chowdhury
title	Nano-Assembly of Quisinostat and Biodegradable Macromolecular Carrier Results in Supramolecular Complexes with Slow-Release Capabilities
title_short	Nano-Assembly of Quisinostat and Biodegradable Macromolecular Carrier Results in Supramolecular Complexes with Slow-Release Capabilities
title_full	Nano-Assembly of Quisinostat and Biodegradable Macromolecular Carrier Results in Supramolecular Complexes with Slow-Release Capabilities
title_fullStr	Nano-Assembly of Quisinostat and Biodegradable Macromolecular Carrier Results in Supramolecular Complexes with Slow-Release Capabilities
title_full_unstemmed	Nano-Assembly of Quisinostat and Biodegradable Macromolecular Carrier Results in Supramolecular Complexes with Slow-Release Capabilities
title_sort	nano-assembly of quisinostat and biodegradable macromolecular carrier results in supramolecular complexes with slow-release capabilities
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/974a39141b1f4bfabaf287a1638f48df
work_keys_str_mv	AT anandachowdhury nanoassemblyofquisinostatandbiodegradablemacromolecularcarrierresultsinsupramolecularcomplexeswithslowreleasecapabilities AT alexandermarin nanoassemblyofquisinostatandbiodegradablemacromolecularcarrierresultsinsupramolecularcomplexeswithslowreleasecapabilities AT davidjweber nanoassemblyofquisinostatandbiodegradablemacromolecularcarrierresultsinsupramolecularcomplexeswithslowreleasecapabilities AT alexanderkandrianov nanoassemblyofquisinostatandbiodegradablemacromolecularcarrierresultsinsupramolecularcomplexeswithslowreleasecapabilities
_version_	1718410850520268800

Nano-Assembly of Quisinostat and Biodegradable Macromolecular Carrier Results in Supramolecular Complexes with Slow-Release Capabilities

Ejemplares similares