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Responsive nanogels for application as smart carriers in endocytic pH-triggered drug delivery systems

机译:响应性纳米凝胶,用作内吞pH触发药物递送系统中的智能载体

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Various specially designed poly(N-isopropylacrylamide-co-acrylic acid) (NIPA-co-AAc) nanogels (NGs) with different NIPA/AAc molar composition were synthesized by precipitation/dispersion polymerization and evaluated as carriers for drug delivery systems (DDSs) of doxorubicin hydrochloride (DOXO-HCl) for cancer therapies. The NGs presented excellent dispersability in physiological environments (pH 7.4 and 5 at 37 degrees C), as shown by dynamic light scattering (DLS). Moreover, the NGs exhibited high drug loading capacity and efficiency due to the ionic interaction of the cationic drug with the anionic NGs. NG-DOXO-HCl formulation presented excellent dispersability in water and minimal leakage of the cargo at plasma simulated medium (pH 7.4 and 0.14 M NaCl) at 37 degrees C and.a triggered release at lysosomal simulated medium (pH 5 and 0.14 M NaCl). This release behavior together with their size and the low cytotoxicity determined by the MTT assay converts these NGs in great candidates for their application as carriers in cancer therapies based on the enhanced permeability and retention effect (EPR) with drug pH-triggered release after endocytosis in tumor cells. (C) 2016 Elsevier Ltd. All rights reserved.
机译:通过沉淀/分散聚合合成了具有不同NIPA / AAc摩尔组成的各种特殊设计的聚(N-异丙基丙烯酰胺-共丙烯酸)(NIPA-co-AAc)纳米凝胶(NGs),并将其评估为药物递送系统(DDS)的载体盐酸阿霉素(DOXO-HCl)用于癌症治疗。如动态光散射(DLS)所示,NG在生理环境(pH 7.4和5在37摄氏度)下表现出出色的分散性。此外,由于阳离子药物与阴离子NGs的离子相互作用,NGs显示出高的载药量和效率。 NG-DOXO-HCl制剂在37°C的血浆模拟培养基(pH 7.4和0.14 M NaCl)下表现出优异的水分散性和最小的货物泄漏,并在溶酶体模拟培养基(pH 5和0.14 M NaCl)下触发释放。这种释放行为连同其大小以及通过MTT分析确定的低细胞毒性将这些NGs转化为非常适合的候选物,可作为它们在癌症治疗中的载体而应用,这是基于增强的通透性和保留作用(EPR),而药物在细胞内吞后通过pH触发释放肿瘤细胞。 (C)2016 Elsevier Ltd.保留所有权利。

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