Polysaccharide Nanoparticles Bearing HDAC Inhibitor as Nontoxic Nanocarrier for Drug Delivery.


Journal

Macromolecular bioscience
ISSN: 1616-5195
Titre abrégé: Macromol Biosci
Pays: Germany
ID NLM: 101135941

Informations de publication

Date de publication:
06 2020
Historique:
received: 06 02 2020
pubmed: 7 4 2020
medline: 3 6 2021
entrez: 7 4 2020
Statut: ppublish

Résumé

The histone deacetylase inhibitors (HDACi) are potent drugs in the treatment of inflammatory diseases and defined cancer types. However, major drawbacks of HDACi, such as valproic acid (VPA), are limited serum half-life, side effects and the short circulation time. Thus, the immobilization of VPA in a polysaccharide matrix is used to circumvent these problems and to design a suitable nanocarrier system. Therefore, VPA is covalently attached to cellulose and dextran via esterification with degree of substitution (DS) values of up to 2.20. The resulting hydrophobic polymers are shaped to spherical nanoparticles (NPs) with hydrodynamic diameter between 138 to 221 nm and polydispersity indices from 0.064 to 0.094 by nanoprecipitation and emulsification technique. Lipase treatment of the NPs leads to in vitro release of VPA and hence to an inhibition of HDAC2 activity in a HDAC2 assay. NPs are rapidly taken up by HeLa cells and mainly localize in the cytoplasm. The NPs are hemocompatible and nontoxic as revealed by the shell-less hen's egg model.

Identifiants

pubmed: 32249554
doi: 10.1002/mabi.202000039
doi:

Substances chimiques

Drug Carriers 0
Histone Deacetylase Inhibitors 0
Polysaccharides 0
HDAC2 protein, human EC 3.5.1.98
Histone Deacetylase 2 EC 3.5.1.98

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2000039

Informations de copyright

© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Auteurs

Henry Lindemann (H)

Friedrich Schiller University Jena, Humboldtstraße 10, Jena, 07743, Germany.

Marie Kühne (M)

Friedrich Schiller University Jena, Hans-Knöll-Straße 2, Jena, 07745, Germany.

Christian Grune (C)

Institute of Pharmacy, Pharmaceutical Technology and Biopharmacy, Friedrich Schiller University Jena, Lessingstraße 8, Jena, 07743, Germany.

Paul Warncke (P)

Institute of Pharmacy, Pharmaceutical Technology and Biopharmacy, Friedrich Schiller University Jena, Lessingstraße 8, Jena, 07743, Germany.

Susanne Hofmann (S)

Friedrich Schiller University Jena, Hans-Knöll-Straße 2, Jena, 07745, Germany.

Andreas Koschella (A)

Friedrich Schiller University Jena, Humboldtstraße 10, Jena, 07743, Germany.

Maren Godmann (M)

Friedrich Schiller University Jena, Hans-Knöll-Straße 2, Jena, 07745, Germany.

Dagmar Fischer (D)

Institute of Pharmacy, Pharmaceutical Technology and Biopharmacy, Friedrich Schiller University Jena, Lessingstraße 8, Jena, 07743, Germany.

Thorsten Heinzel (T)

Friedrich Schiller University Jena, Hans-Knöll-Straße 2, Jena, 07745, Germany.

Thomas Heinze (T)

Friedrich Schiller University Jena, Humboldtstraße 10, Jena, 07743, Germany.

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