A safety and tolerability study of differently-charged nanoparticles for local pulmonary drug delivery
A safety and tolerability study of differently-charged nanoparticles for local pulmonary drug delivery
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DOI：
10.1016/j.taap.2010.04.011
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发表时间：
2010-07-01
影响因子：
3.8
通讯作者：
Benita, Simon
中科院分区：
文献类型：
--
作者：
Harush-Frenkel, Oshrat;Bivas-Benita, Maytal;Benita, Simon
基于纳米颗粒（NP）的药物递送系统在肺部疾病的治疗中提供了有希望的机会。在这里，我们检查了肺部递送的由PEG-PLA组成的NP的安全性和耐受性作为颗粒表面电荷的函数。这种比较的基本原理应归因于带正电荷和带负电荷的PEG-PLA NP的不同肺毒性。因此，在每天气管内滴注5天后，研究肺部施用的NP对BALB/c小鼠的局部和全身作用，所述小鼠在实验的第八或第十九天被安乐死。我们收集支气管肺泡灌洗液，并研究血液学和组织化学参数。值得注意的是，基于阳离子硬脂胺的PEG-PLA NP在第8天和第19天引起增加的局部和全身毒性作用。相比之下，类似大小的阴离子NP的耐受性要好得多，仅在肺灌注后的第八个实验天观察到局部炎症作用。未观察到全身毒性作用，但观察到血小板计数中度变化，认为不具有临床意义。滴注阴离子NP后，在内脏器官中未检测到病理学观察结果。总之，这些观察结果表明，阴离子PEG-PLA纳米颗粒是有用的肺部药物载体，应该被认为是一个有前途的治疗药物递送系统。(C)2010年爱思唯尔公司All rights reserved.
Nanoparticle (NP) based drug delivery systems provide promising opportunities in the treatment of lung diseases. Here we examined the safety and tolerability of pulmonary delivered NPs consisting of PEG-PLA as a function of particle surface charge. The rationale for such a comparison should be attributed to the differential pulmonary toxicity of positively and negatively charged PEG-PLA NP. Thus, the local and systemic effects of pulmonary administered NPs were investigated following 5 days of daily endotracheal instillation to BALB/c mice that were euthanized on the eighth or nineteenth day of the experiment. We collected bronchoalveolar lavages and studied hematological as well as histochemistry parameters. Notably, the cationic stearylamine based PEG-PLA NPs elicited increased local and systemic toxic effects both on the eighth and nineteenth day. In contrast, anionic NPs of similar size were much better tolerated with local inflammatory effects observed only on the eighth experimental day after pulmonary instillation. No systemic toxicity effect was observed although a moderate change was noted in the platelet count that was not considered to be of clinical significance. No pathological observations were detected in the internal organs following instillation of anionic NPs. Overall these observations suggest that anionic PEG-PLA NPs are useful pulmonary drug carriers that should be considered as a promising therapeutic drug delivery system. (C) 2010 Elsevier Inc. All rights reserved.