Nanotechnology Characterization Laboratory, Advanced Technology Program, SAIC-Frederick Inc., NCI-Frederick, PO Box B, Frederick, MD 21702, USA.
J Control Release. 2010 Sep 1;146(2):164-74. doi: 10.1016/j.jconrel.2010.04.008. Epub 2010 Apr 10.
There are many important considerations during preclinical development of cancer nanomedicines, including: 1) unique aspects of animal study design; 2) the difficulties in evaluating biological potency, especially for complex formulations; 3) the importance of analytical methods that can determine platform stability in vivo, and differentiate bound and free active pharmaceutical ingredient (API) in biological matrices; and 4) the appropriateness of current dose scaling techniques for estimation of clinical first-in-man dose from preclinical data. Biologics share many commonalities with nanotechnology products with regard to complexity and biological attributes, and can, in some cases, provide context for dealing with these preclinical issues. In other instances, such as the case of in vivo stability analysis, new approaches are required. This paper will discuss the significance of these preclinical issues, and present examples of current methods and best practices for addressing them. Where possible, these recommendations are justified using the existing regulatory guidance literature.
在癌症纳米药物的临床前开发过程中有许多需要考虑的重要因素，包括：1）动物研究设计的独特方面；2）评估生物效力的困难，特别是对于复杂制剂；3）分析方法的重要性，这些方法可以确定体内平台的稳定性，并区分生物基质中结合的和游离的有效药物成分（API）；4）当前剂量缩放技术是否适合从临床前数据估算临床首次人体剂量。生物制品在复杂性和生物学特性方面与纳米技术产品有许多共同之处，在某些情况下，可以为解决这些临床前问题提供背景。在其他情况下，例如体内稳定性分析，需要采用新方法。本文将讨论这些临床前问题的重要性，并介绍当前解决这些问题的方法和最佳实践的实例。在可能的情况下，这些建议使用现有的监管指导文献进行了论证。
