Vascular Drug Delivery Using Carrier Red Blood Cells: Focus on RBC Surface Loading and Pharmacokinetics
Patrick M. Glassman, Carlos H. Villa, Anvay Ukidve, Zongmin Zhao, Paige N. Smith, Samir Mitragotri, Alan J. Russell, Jacob S. Brenner, Vladimir R. Muzykantov
Abstract
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.