Drug transport by red blood cells

Abstract

This review focuses on the role of human red blood cells (RBCs) as drug carriers. First, a general introduction about RBC physiology is provided, followed by the presentation of several cases in which RBCs act as natural carriers of drugs. This is due to the presence of several binding sites within the same RBCs and is regulated by the diffusion of selected compounds through the RBC membrane and by the presence of influx and efflux transporters. The balance between the influx/efflux and the affinity for these binding sites will finally affect drug partitioning. Thereafter, a brief mention of the pharmacokinetic profile of drugs with such a partitioning is given. Finally, some examples in which these natural features of human RBCs can be further exploited to engineer RBCs by the encapsulation of drugs, metabolites, or target proteins are reported. For instance, metabolic pathways can be powered by increasing key metabolites (i.e., 2,3-bisphosphoglycerate) that affect oxygen release potentially useful in transfusion medicine. On the other hand, the RBC pre-loading of recombinant immunophilins permits increasing the binding and transport of immunosuppressive drugs. In conclusion, RBCs are natural carriers for different kinds of metabolites and several drugs. However, they can be opportunely further modified to optimize and improve their ability to perform as drug vehicles.

Back to the Basics of SARS-CoV-2 Biochemistry: Microvascular Occlusive Glycan Bindings Govern Its Morbidities and Inform Therapeutic Responses

“…This effect also proved to apply to dozens of other drugs [ 126 , 127 ] and bioactive agents [ 128 ], with blood-to-plasma ratios greater than 10 for several [ 126 , 127 , 128 ]. Such binding of drugs and other bioactive agents to RBCs provides extended persistence in circulation [ 127 ], with increased opportunity for physiological potency beyond what concentration values in plasma would indicate. Yet this effect has been obscurely reported, pharmacokinetic parameters are still typically detected only in plasma or serum, and erroneous values of significant consequence have been reported for SARS-CoV-2 SP and for another bioactive molecule considered in the next section.…”

“…This RBC-binding effect proved not to apply for IVM [122], but it did apply for rapamycin, a widely used drug that is a chemical cousin of IVM, which has a striking, 30-fold ratio of whole-blood-to-plasma concentrations [123][124][125]. This effect also proved to apply to dozens of other drugs [126,127] and bioactive agents [128], with blood-to-plasma ratios greater than 10 for several [126][127][128]. Such binding of drugs and other bioactive agents to RBCs provides extended persistence in circulation [127], with increased opportunity for physiological potency beyond what concentration values in plasma would indicate.…”

Efficient and highly reproducible production of red blood cell-derived extracellular vesicle mimetics for the loading and delivery of RNA molecules

“…Red Blood Cells (RBCs) have long been used in transfusion medicine and, more recently, as drug delivery systems. A large number of preclinical and clinical applications rely on their unique biological features that: (1) permits easily obtaining these cells from any donor or patients, including children, in large amounts, repeatedly and without harming the donor, and, (2) following the discovery that RBCs can be modified by the encapsulation of active agents for several biomedical applications already in the late stages of clinical development 6 – 10 . For this reason, they can be considered one of the most useful sources for EV development.…”