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.
Highlights
The idea of using red blood cells (RBC) as carriers for drug delivery initially emerged about half a century ago as an approach to improve enzyme replacement therapy [1]
For almost 50 years, academic researchers have been intrigued by the potential of using autologous Red blood cells (RBC) as a drug delivery system for a myriad of therapeutics
Attachment of drugs to the RBC can lead to unprecedented changes in circulation time, biodistribution, elimination pathways, pharmacodynamics, and immunogenicity
Summary
The idea of using red blood cells (RBC) as carriers for drug delivery initially emerged about half a century ago as an approach to improve enzyme replacement therapy [1]. Approaches to use RBCs as carriers for pharmacological agents have recently gained significant and rapidly growing attention Progress in this field is rapidly diversifying and accelerating towards potentially clinically useful products. Novel advanced strategies are emerging, including genetic molecular modifications of RBC [2,3], modulation of the immune system by RBC-coupled antigens [3,4], and vascular transfer of RBC-coupled nanocarriers (RBC hitchhiking) [5,6,7] Both encapsulation into and coupling to the surface of RBC fundamentally transform the key parameters of absorption, distribution, metabolism, and elimination (ADME) of drugs and drug delivery systems (DDS), including diverse nanocarriers. Our goal is to provide the modular framework for experimental and theoretical pre-clinical and clinical investigations of ADME-PK-PD features of RBC-based drug delivery
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