HI 6 human serum albumin nanoparticles-Development and transport over an in vitro blood-brain barrier model
HI 6 human serum albumin nanoparticles-Development and transport over an in vitro blood-brain barrier model
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DOI：
10.1016/j.toxlet.2011.06.027
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发表时间：
2011-09-25
影响因子：
3.5
通讯作者：
Kreuter, Joerg
中科院分区：
文献类型：
--
作者：
Dadparvar, Miriam;Wagner, Sylvia;Kreuter, Joerg
有机磷(OP)化合物中毒的标准治疗包括使用作为乙酰胆碱酯酶(AChE)再激活解毒剂的肟类药物。然而，血脑屏障(BBB)限制了这些药物从血液中快速进入大脑的治疗相关浓度。由于人血清白蛋白(HSA)纳米颗粒能够通过血脑屏障将各种药物输送到大脑中。在本研究中，HI-6二甲基磺酸盐和HI-6一水合物被结合到这些纳米粒子上。所得吸附等温线与Freundlich的经验吸附等温线比与Langmuir的吸附等温线更符合。在pH为8.3时，测得HI-6二甲磺酸盐和HI-6一水合氯化物的最大药物结合容量分别为每毫克纳米粒344.8和322.6微克。这些计算值高于先前研究中测定的人血清白蛋白纳米粒对奥比磷定的吸附容量93.5微克/毫克。在原代猪脑毛细血管内皮细胞(PBCEC)中进行的纳米颗粒肟制剂的体外测试表明，OP抑制的AChE的复活能力是游离肟的两倍。这些发现表明，即使在中枢神经系统(CNS)内，HSA制成的纳米颗粒也可以用HI 6衍生物实现足够的解毒剂OP中毒治疗。(C)2011爱思唯尔爱尔兰有限公司。保留所有权利。
The standard treatment of intoxication with organophosphorus (OP) compounds includes the administration of oximes acting as acetylcholinesterase (AChE) reactivating antidotes. However, the blood-brain barrier (BBB) restricts the rapid transport of these drugs from the blood into the brain in therapeutically relevant concentrations. Since human serum albumin (HSA) nanoparticles enable the delivery of a variety of drugs across the BBB into the brain. HI 6 dimethanesulfonate and HI 6 dichloride monohydrate were bound to these nanoparticles in the present study. The resulting sorption isotherms showed a better fit to Freundlich's empirical adsorption isotherm than to Langmuir's adsorption isotherm. At the pH of 8.3 maximum drug binding capacities of 344.8 mu g and 322.6 mu g per mg of nanoparticles were calculated for HI 6 dimethanesulfonate and HI 6 dichloride monohydrate, respectively. These calculated values are higher than the adsorption capacity of 93.5 mu g/mg for obidoxime onto HSA nanoparticles determined in a previous study. In vitro testing of the nanoparticulate oxime formulations in primary porcine brain capillary endothelial cells (pBCEC) demonstrated an up to two times higher reactivation of OP-inhibited AChE than the free oximes. These findings show that nanoparticles made of HSA may enable a sufficient antidote OP-poisoning therapy with HI 6 derivatives even within the central nervous system (CNS). (C) 2011 Elsevier Ireland Ltd. All rights reserved.