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.

中文翻译：

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具有HDAC抑制剂的多糖纳米颗粒可作为无毒纳米载体用于药物输送。

组蛋白脱乙酰基酶抑制剂（HDACi）是治疗炎性疾病和特定癌症类型的有效药物。但是，HDACi的主要缺点（例如丙戊酸（VPA））受限于血清半衰期，副作用和循环时间短。因此，将VPA固定在多糖基质中可避免这些问题并设计合适的纳米载体系统。因此，VPA通过酯化共价连接到纤维素和右旋糖酐，取代度（DS）值最高为2.20。通过纳米沉淀和乳化技术，将得到的疏水性聚合物成形为流体动力学直径在138至221 nm之间，多分散指数为0.064至0.094的球形纳米颗粒（NPs）。NP的脂肪酶处理会导致VPA的体外释放，从而导致在HDAC2分析中抑制HDAC2活性。NP被HeLa细胞迅速吸收，并且主要定位在细胞质中。如无壳母鸡的卵模型所揭示的，NP具有血液相容性且无毒。