NMR Assessment of the High Order Structure of Biological Therapeutics in Erythrocytes Provides a Tool for Drug Delivery Design

An effective delivery system is crucial for ensuring the therapeutic efficacy of a drug. This is especially true for biological drugs, which possess unique physicochemical properties and complex pharmacokinetic profiles, and thus require a dedicated design. Whole erythrocytes, and more recently, nanoparticles derived from red blood cells (RBCs), have been used in preclinical studies to deliver biological therapeutics: their biocompatibility and extended circulation time help prevent immunogenicity and reduce clearance and toxicity. However, characterizing such complex systems poses challenges that complicate their development and optimization. We argue that NMR spectroscopy enables the monitoring of the preservation of the high order structure of the encapsulated proteins, as well as their concentration, thereby assisting in formulation design, development, and manufacturing.