Toxicity of polyamidoamine dendrimers in vivo

A. Stanavaya, V. Abashkin, A. Vcherashniaya, M. Terehova, V. Zhogla, I. Halets-Bui, S. S. Zhyvitskaya, Dzmitry G. Shcharbin
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Abstract

The development of effective drug delivery systems is a crusial task for modern medicine. The main problem is the occurrence of non-specific toxicity leading to undesirable side effects in vivo.This article aims at reviewing resent research on the toxicity of polyamidoamine (PAMAM) dendrimers in vivo. The research results show that the toxicity of PAMAM dendrimers and modified nanoparticles depends both on the characteristics of the particles themselves (size, generation and surface charge) and on the administration parameters. It has been shown that cationic PAMAM dendrimers of small and medium generations are non-toxic in vivo when administered intravenously and intraperitoneally to mice at doses up to 10 mg/kg. In turn, anionic, neutral, and modified PAMAM dendrimers do not exhibit toxicity, regardless of the route of administration. Thus, by varying methods of administration, the dose, and modifying the surface of dendrimers, the decrease in toxicity can be achieved, promising a path towards their successfully aplication as drug carriers.
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聚胺胺树状大分子的体内毒性
开发有效的给药系统是现代医学的一项重要任务。主要问题是在体内发生非特异性毒性,导致不良的副作用。本文综述了近年来聚胺胺(PAMAM)树状大分子的体内毒性研究进展。研究结果表明,PAMAM树状大分子和修饰纳米颗粒的毒性既取决于颗粒本身的特性(大小、生成和表面电荷),也取决于给药参数。研究表明,当以高达10 mg/kg的剂量静脉注射和腹腔注射给小鼠时,小代和中代的阳离子PAMAM树状大分子在体内无毒。反过来,阴离子、中性和改性PAMAM树状大分子不表现出毒性,无论给药途径如何。因此,通过不同的给药方法、剂量和修饰树状大分子的表面,可以实现毒性的降低,这为它们作为药物载体的成功应用提供了一条途径。
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