Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA, 90095, USA.
California NanoSystems Institute, University of California, Los Angeles, CA, 90095, USA.
Small. 2020 Sep;16(36):e2000673. doi: 10.1002/smll.202000673. Epub 2020 May 14.
The rate of translational effort of nanomedicine requires strategic planning of nanosafety research in order to enable clinical trials and safe use of nanomedicine in patients. Herein, the experiences that have emerged based on the safety data of classic liposomal formulations in the space of oncology are discussed, along with a description of the new challenges that need to be addressed according to the rapid expansion of nanomedicine platform beyond liposomes. It is valuable to consider the combined use of predictive toxicological assessment supported by deliberate investigation on aspects such as absorption, distribution, metabolism, and excretion (ADME) and toxicokinetic profiles, the risk that may be introduced during nanomanufacture, unique nanomaterials properties, and nonobvious nanosafety endpoints, for example. These efforts will allow the generation of investigational new drug-enabling safety data that can be incorporated into a rational infrastructure for regulatory decision-making. Since the safety assessment relates to nanomaterials, the investigation should cover the important physicochemical properties of the material that may lead to hazards when the nanomedicine product is utilized in humans.
纳米医学的转化效率要求对纳米安全研究进行战略规划,以便能够在临床试验中以及在患者中安全使用纳米医学。本文讨论了基于肿瘤学领域经典脂质体制剂的安全性数据所获得的经验,同时还描述了根据纳米医学平台超越脂质体的快速扩展而需要解决的新挑战。考虑到结合使用基于吸收、分布、代谢和排泄(ADME)和毒代动力学特征等方面的深思熟虑的研究来进行预测性毒理学评估,以及在纳米制造过程中可能引入的风险、独特的纳米材料特性和不明显的纳米安全性终点等因素,这是有价值的。这些努力将允许生成可纳入用于监管决策的合理基础设施的新药研究使能安全性数据。由于安全性评估涉及纳米材料,因此调查应涵盖可能导致纳米医学产品在人类中使用时出现危害的材料的重要物理化学特性。