Pharmacological chaperones (PCs) are low-molecular weight chemical molecules used in patients for the treatment of some rare diseases caused primarily by protein instability. A controlled and on-demand release of PCs via nanoparticles is an alternative for cases in which long treatments are needed and prolonged oral administration could have adverse effects. In this work, pyrimethamine (PYR), which is a potent PC consisting of pyrimidine-2,4-diamine substituted at position 5 by a p-chlorophenyl group and at position 6 by an ethyl group, was successfully loaded in electroresponsive poly(3,4-ethylenedioxythiophene) nanoparticles (PEDOT NPs). The PYR-loading capacity was 11.4 ± 1.5%, with both loaded and unloaded PEDOT NPs exhibiting similar sizes (215 ± 3 and 203 ± 1 nm, respectively) and net surface charges (−26 ± 7 and −29 ± 6 mV, respectively). In the absence of electrical stimulus, the release of PC from loaded NPs is very low (1.6% in 24 h and 18% in 80 days) in aqueous environments. Instead, electrical stimuli that sustained for 30 min enhanced the release of PYR, which was ∼50% when the voltage was scanned from –0.5 V to 0.5 V (cyclic voltammetry) and ∼35% when a constant voltage of 1.0 V was applied (chronoamperometry).

中文翻译：

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导电聚合物纳米粒子用于电压控制释放的药理伴侣

药理分子伴侣（PCs）是用于患者的低分子量化学分子，用于治疗一些主要由蛋白质不稳定引起的罕见疾病。通过纳米粒子控制和按需释放PC是需要长期治疗且长时间口服可能产生不利影响的情况的替代方法。在这项工作中，乙胺嘧啶（PYR）是一种有效的PC，由在第5位被p取代的嘧啶-2,4-二胺组成-氯苯基和在6位上的乙基被成功装载到电响应性聚（3,4-乙撑二氧噻吩）纳米颗粒（PEDOT NPs）中。PYR的负载能力为11.4±1.5％，已加载和未加载的PEDOT NP都显示出相似的大小（分别为215±3和203±1 nm）和净表面电荷（分别为-26±7和-29±6 mV） ）。在没有电刺激的情况下，在水性环境中，PC从负载的NP中释放的比例非常低（24小时为1.6％，80天为18％）。相反，持续30分钟的电刺激会增强PYR的释放，当电压从–0.5 V扫描至0.5 V（循环伏安法）时约为50％，而施加1.0 V恒定电压时约为35％（计时电流法）。