Nanotechnology Characterization Laboratory, Advanced Technology Program, SAIC-Frederick Inc., NCI-Frederick, Frederick, MD 21702, USA.
J Control Release. 2013 Dec 10;172(2):456-66. doi: 10.1016/j.jconrel.2013.05.025. Epub 2013 Jun 3.
Preclinical characterization of novel nanotechnology-based formulations is often challenged by physicochemical characteristics, sterility/sterilization issues, safety and efficacy. Such challenges are not unique to nanomedicine, as they are common in the development of small and macromolecular drugs. However, due to the lack of a general consensus on critical characterization parameters, a shortage of harmonized protocols to support testing, and the vast variety of engineered nanomaterials, the translation of nanomedicines into clinic is particularly complex. Understanding the immune compatibility of nanoformulations has been identified as one of the important factors in (pre)clinical development and requires reliable in vitro and in vivo immunotoxicity tests. The generally low sensitivity of standard in vivo toxicity tests to immunotoxicities, inter-species variability in the structure and function of the immune system, high costs and relatively low throughput of in vivo tests, and ethical concerns about animal use underscore the need for trustworthy in vitro assays. Here, we consider the correlation (or lack thereof) between in vitro and in vivo immunotoxicity tests as a mean to identify useful in vitro assays. We review literature examples and case studies from the experience of the NCI Nanotechnology Characterization Lab, and highlight assays where predictability has been demonstrated for a variety of nanomaterials and assays with high potential for predictability in vivo.
新型纳米技术制剂的临床前特性通常受到理化特性、无菌/灭菌问题、安全性和功效的挑战。这些挑战不仅存在于纳米医学中，因为它们在小分子和大分子药物的开发中也很常见。然而，由于缺乏对关键特性参数的普遍共识、缺乏支持测试的协调协议，以及工程纳米材料的多样性，纳米医学向临床的转化尤其复杂。了解纳米制剂的免疫相容性已被确定为（临床前）临床开发的重要因素之一，需要可靠的体外和体内免疫毒性测试。标准体内毒性测试对免疫毒性的敏感性通常较低，免疫系统的结构和功能在物种间存在差异，体内测试的成本高、通量相对较低，以及对动物使用的伦理问题，这些都凸显了对可靠的体外检测的需求。在这里，我们考虑了体外和体内免疫毒性测试之间的相关性（或缺乏相关性），作为识别有用的体外检测的一种手段。我们回顾了 NCI 纳米技术特性实验室的文献实例和案例研究，并强调了在各种纳米材料和具有高体内预测潜力的检测中已经证明了可预测性的检测。
