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

**Authors:** Luis Padilla-Cortés, Giulia Roxana Gheorghita, Francesco Currò, Rebecca Calamandrei, Bianca Susini, Sara Callozzo, Giulia Crivello, Pasquale Russomanno, Enrico Ravera, Linda Cerofolini, Marco Fragai

PMC · DOI: 10.1021/jacs.5c05617 · Journal of the American Chemical Society · 2025-07-16

## TL;DR

This paper shows how NMR can track the structure and concentration of biological drugs inside red blood cells, helping improve drug delivery design.

## Contribution

The novel use of NMR spectroscopy to assess high-order protein structure in erythrocyte-based drug delivery systems is introduced.

## Key findings

- NMR spectroscopy can monitor the structural integrity of encapsulated proteins in erythrocytes.
- The method helps in optimizing formulation design and manufacturing of biological therapeutics.
- The approach addresses challenges in characterizing complex drug delivery systems.

## Abstract

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.

## Full-text entities

- **Diseases:** toxicity (MESH:D064420)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12314899/full.md

## References

60 references — full list in the complete paper: https://tomesphere.com/paper/PMC12314899/full.md

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Source: https://tomesphere.com/paper/PMC12314899