Glassman Patrick M, Villa Carlos H, Ukidve Anvay, Zhao Zongmin, Smith Paige, Mitragotri Samir, Russell Alan J, Brenner Jacob S, Muzykantov Vladimir R
Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania; Philadelphia, PA 19104, USA.
John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Pharmaceutics. 2020 May 9;12(5):440. doi: 10.3390/pharmaceutics12050440.
Red blood cells (RBC) have great potential as drug delivery systems, capable of producing unprecedented changes in pharmacokinetics, pharmacodynamics, and immunogenicity. Despite this great potential and nearly 50 years of research, it is only recently that RBC-mediated drug delivery has begun to move out of the academic lab and into industrial drug development. RBC loading with drugs can be performed in several ways-either via encapsulation within the RBC or surface coupling, and either ex vivo or in vivo-depending on the intended application. In this review, we briefly summarize currently used technologies for RBC loading/coupling with an eye on how pharmacokinetics is impacted. Additionally, we provide a detailed description of key ADME (absorption, distribution, metabolism, elimination) changes that would be expected for RBC-associated drugs and address unique features of RBC pharmacokinetics. As thorough understanding of pharmacokinetics is critical in successful translation to the clinic, we expect that this review will provide a jumping off point for further investigations into this area.
红细胞(RBC)作为药物递送系统具有巨大潜力,能够在药代动力学、药效学和免疫原性方面产生前所未有的变化。尽管具有这种巨大潜力且经过了近50年的研究,但直到最近,红细胞介导的药物递送才开始走出学术实验室,进入工业药物开发领域。用药物加载红细胞可以通过几种方式进行——要么通过包裹在红细胞内,要么通过表面偶联,并且可以在体外或体内进行——这取决于预期的应用。在这篇综述中,我们简要总结了目前用于红细胞加载/偶联的技术,并关注其对药代动力学的影响。此外,我们详细描述了与红细胞相关药物预期的关键ADME(吸收、分布、代谢、排泄)变化,并阐述了红细胞药代动力学的独特特征。由于对药代动力学的透彻理解对于成功转化到临床至关重要,我们期望这篇综述将为该领域的进一步研究提供一个起点。