Polysaccharide Nanoparticles Bearing HDAC Inhibitor as Nontoxic Nanocarrier for Drug Delivery

Abstract

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.

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

“…To date most of the research activity in the field has been focused on efforts of encapsulating quisinostat into various drug carriers. To that end, various macromolecular systems have been explored, such as nanoparticles on the basis of poly(lactide)-blockpoly(ethylene glycol) [15], poly (lactide-co-glycolide)-lecithin-poly(ethylene glycol) [6], and polysaccharide [16], as well as matrices composed of β-cyclodextrin-poly (β-amino ester) networks [17] and bioerodible radiopaque hydrogels [14]. Despite offering multiple distinct advantages, all of these methods usually involve sophisticated chemical and formulation approaches and require multi-step production processes.…”

Polysaccharide nanoparticles: from fabrication to applications

“…valproic acid. 225 The acid was attached via esterification and NPs formed via nanoprecipitation or emulsion method. The formed particles could be used for valproate release via enzymatic cleavage of the ester bond, which was studied in vitro and in shell-less Hen's egg tests.…”

Nanomedicine to Overcome Multidrug Resistance Mechanisms in Colon and Pancreatic Cancer: Recent Progress

“…Accordingly, Gd-metallofullerenol nanomaterials were able to inhibit the interaction between histone deacetylase I (HDAC1) and metastasis-associated protein (MTA1), suppressing cell invasion and metastasis in PAC [ 162 ]. Valproic acid, an HDAC2 inhibitor, was encapsulated in polysaccharide NPs, allowing its hemocompatibility and avoiding toxicity [ 163 ]. In addition, other HDAC inhibitors, such as vorinostat and quisinostat, were associated with PLGA-lecithin-PEG NPs to increase the radiosensitization of these tumors [ 164 ].…”