Biocompatible sulfated valproic acid-coupled polysaccharide-based nanocarriers with HDAC inhibitory activity

in: Journal of Controlled Release (2021)
Kühne, Marie; Lindemann, Henry; Grune, Christian; Schröder, Daniel; Cseresnyes, Zoltan; Godmann, Maren; Koschella, Andreas; Figge, Marc Thilo; Eggeling, Christian; Fischer, Dagmar; Heinze, Thomas; Heinzel, Thorsten
The development of bio-based nanoparticles (NPs) as drug containers is of increasing interest to circumvent several obstacles in drug therapy such as rapid drug metabolization, short serum half-life, and unspecific side effects. The histone deacetylase inhibitor valproic acid (VPA) is known for its anti-inflammatory as well as for its anti-cancer activity. Here, recently developed VPA-loaded NPs based on cellulose- and dextran VPA esters were modified with sulfuric acid half ester moieties to improve intracellular drug release. The NPs show rapid cellular uptake, are non-toxic in vitro and in vivo, and able to induce histone H3 hyperacetylation. Thus, they represent a potent drug delivery system for the application in a variety of treatment settings, such as inflammation, sepsis and defined cancer types. In addition, the flexible NP-system offers a broad range of further options for modification, e.g. for targeting strategies and multi-drug approaches.

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