首页> 外文期刊>Environmental toxicology and pharmacology >In vivo lung deposition and sub-acute inhalation toxicity studies of nano-sized alendronate sodium as an antidote for inhaled toxic substances in Sprague Dawley rats
【24h】

In vivo lung deposition and sub-acute inhalation toxicity studies of nano-sized alendronate sodium as an antidote for inhaled toxic substances in Sprague Dawley rats

机译:纳米阿仑膦酸钠作为Sprague Dawley大鼠吸入有毒物质的解毒剂的体内肺沉积和亚急性吸入毒性研究

获取原文
获取原文并翻译 | 示例
       

摘要

Introduction: Alendronate sodium is a bisphosphonate agent used for the treatment of osteoporosis and other bone diseases. It has a strong chelating property to bind or, to some extent, counteract the effects of substances, such as magnesium, calcium citrate, ferrous fumarate, carbonyl iron, as well as the zinc gluconate, sulfate and acetate salts. The objective of the present study was to evaluate lung deposition and sub-acute inhalation toxicity of the alendronate sodium respiratory formulation. Methods: Particle dimension of aerosols of alendronate was measured using a particle size analyzer. Alendronate was radiolabeled using Technetium-99m for in vitro and in vivo biodistribution studies. Alendronate at doses, 0.5%, 1.0%, and 1.5% in ethanol-saline respiratory formulation was inhaled twice a day up to 5 weeks for inhalation toxicity investigations. Hematological, biochemical and lung toxicity biomarkers in bronchoalveolar lavage (BAL) fluid were determined at the end of the experiment. Histopathological analysis of lung tissues was carried out to observe any microscopic changes Results: Particle size analysis revealed the size within 300-500 nm. Anderson cascade impactor results showed that the particles exhibited higher respirable fraction (55.52%) with MMAD of 4.66 μm. Hematology, serum biochemistry and lung toxicity biomarkers in BAL fluid performed in the sub-acute toxicity studies indicated no adverse effects of alendronate sodium inhalation except for a significant increase in cholesterol levels and marginal increase in BAL fluid protein. At autopsy, no histopathological changes in major organs were observed.Conclusions: The lung deposition and safety evaluation data observed from these studies suggested that aerosolized nanosized alendronate sodium by the inhalation route could be a new and promising route of administration as an antidote to radioactive substances through an increase in the bioavailability of the drug as well as a decrease in side effects on systemic delivery.
机译:简介:阿仑膦酸钠是用于治疗骨质疏松症和其他骨骼疾病的双膦酸盐药物。它具有很强的螯合性能,可以结合或在某种程度上抵消诸如镁,柠檬酸钙,富马酸亚铁,羰基铁以及葡萄糖酸锌,硫酸盐和乙酸盐等物质的作用。本研究的目的是评估阿仑膦酸钠呼吸道制剂的肺部沉积和亚急性吸入毒性。方法:使用粒度分析仪测量阿仑膦酸盐气雾剂的颗粒尺寸。使用Technetium-99m对阿仑膦酸盐进行了放射性标记,用于体外和体内生物分布研究。在乙醇-盐水呼吸制剂中,分别以0.5%,1.0%和1.5%的剂量服用阿仑膦酸盐,每天两次,直至5周,以进行吸入毒性研究。在实验结束时确定支气管肺泡灌洗液中的血液学,生化和肺毒性生物标志物。进行肺组织的组织病理学分析以观察任何微观变化。结果:粒度分析揭示了300-500nm内的大小。 Anderson级联撞击器的结果表明,在MMAD为4.66μm的情况下,颗粒表现出较高的可吸入分数(55.52%)。在亚急性毒性研究中进行的BAL液的血液学,血清生化指标和肺毒性生物标志物表明,除了胆固醇水平显着升高和BAL液蛋白的少量升高外,吸入阿仑膦酸钠无不良影响。尸检时未观察到主要器官的组织病理学变化。结论:从这些研究中观察到的肺部沉积和安全性评估数据表明,通过吸入途径雾化的纳米级阿仑膦酸钠雾化可能是一种新的有希望的给药途径,作为放射性物质的解毒剂通过增加药物的生物利用度以及减少对全身递送的副作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号