Nanomedicine can be improved with appropriate and more predictive in vitro tests

Messenger RNA (mRNA) vaccines are an excellent example of the promising field of nanomedicine. But advances in the design and application of nanoparticles as efficient delivery vehicles for biopharmaceuticals containing nucleic acid or protein drugs is, unfortunately, remarkably slow.

A recent obstacle to drug delivery research is a weak correlation observed between in vitro (outside a living organism) and in vivo (inside a living organism) performance. This issue was unclear in the early stages, when cellular delivery of a drug nanocarrier was tested primarily in standard cell culture. With the emergence of advanced in vivo pharmacological studies in mice or human patients, the low reliability and validity of cell culture assays for therapeutic applications becomes evident.

When nanoparticles are applied intravenously, they encounter several obstacles that differ from in vitro situations, such as when they encounter blood components. Nanoparticles are generally coated with a biomolecular multilayer (a protein crown), which modifies the physiochemical properties, pharmacokinetics and toxicity profile of the nanoparticles.

In Biophysics Reviews, from AIP Publishing, German researchers provide a state-of-the-art characterization of the protein corona formed around nanoparticles and its impact on the physicochemical and biological properties of these nanoparticles.

When predicting in vivo performance from in vitro data, it is recommended to combine several analytical and biological characterization methods to obtain a more detailed insight into the in vivo characteristics and behavior of nanoparticles.

Simone Berger, co-author, Ludwig Maximilian University, Munich

The choice of biofluid – serum, plasma or whole blood and of animal origin – and the establishment of standardized protocols are of great importance for more consistent, robust and comprehensive preclinical studies in order to derive structure-activity relationships and in vitro/in vivo correlations.

“The insights gained into protein corona formation can be exploited to optimize supports for nanomedical application,” Berger said.

Information such as in vivo biodistribution and off-target effects cannot be obtained from in vitro experiments, the researchers point out. But new high-throughput screening methods like the barcode system can make in vivo investigations more efficient, economical and ethical.

Some uncertainty remains about the translatability from small to large animals and humans, but bioinformatics could help identify the best-fit animal models for certain diseases.

“Alternatives to animal models, such as ‘human organ-on-a-chip’ microfluidic technology or computational predictions, may be promising strategies to replace animal studies in the future,” Berger said.

Nanomedicine shows “great potential to revolutionize the therapeutic landscape with a wide range of applications like cancer vaccines/immunotherapy or treatment of genetic disorders,” Berger said. “With appropriate and more predictive in vitro tests, the preclinical pipeline will become more efficient, faster and more economical. And most importantly, animal experiments can be replaced or at least reduced.”