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Nanomedicines can be improved with appropriate and more predictive in vitro assays

Nanomedicines can be improved with appropriate and more predictive in vitro assays

 


Messenger RNA (mRNA) vaccines are a prime example of a promising field of nanomedicine.However, advances in the design and application of nanoparticles as efficient delivery media for biopharmaceutics, including: Nucleic acid Or protein drug substances are, unfortunately, significantly slower.

One of the recent obstacles to drug delivery research is the observation of a weak correlation between in vitro and in vivo performance. This problem was not apparent in the early stages when cell delivery of drug nanocarriers was tested primarily in standard cell cultures. Advanced pharmacological in vivo studies emerging in mouse or human patients are revealing the low reliability and validity of cell culture tests for therapeutic applications.

Intravenous administration of nanoparticles presents some obstacles that differ from the in vitro situation, such as contact with blood components. Nanoparticles are usually covered with a multi-layered biomolecule (protein corona). This changes the physicochemical properties, pharmacokinetics, and toxicity profile of nanoparticles.

In AIP Publishing’s Biophysics Reviews, German researchers provide state-of-the-art characterization of the protein corona formed around nanoparticles and their 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 gain more detailed insight into the in vivo properties and behavior of nanoparticles. “

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

Selection of biofluids (serum, plasma, or whole blood, and animals of origin) and establishment of standardized protocols are more consistent, robust, and comprehensive for deriving structural activity correlations and in vitro /. Very important for preclinical trials. In vivo correlation.

“The knowledge gained about protein corona formation can be used to optimize carriers for nanomedical applications,” says Berger.

Researchers have pointed out that information such as in vivo biodistribution and off-target effects cannot be obtained from in vitro experiments. However, new high-throughput screening methods such as barcode systems can make in vivo research more effective, economical, and ethical.

Although some uncertainty remains about the translatability from small animals to large animals and humans, bioinformatics can help identify the optimal animal model for a particular disease.

“Animal model alternatives, such as microfluidic’human organ-on-chip’technology and computational predictions, could be promising strategies to replace animal testing in the future,” Berger said.

Nanomedicines “show great potential to revolutionize the therapeutic environment in a wide range of applications, including cancer vaccines / immunotherapy and the treatment of hereditary diseases,” Berger said. “Appropriate and more predictive in vitro assays make preclinical pipelines more efficient, rapid, and economical, and, importantly, can replace or at least reduce animal testing.”

Source:

Journal reference:

Burger, S. , et al. (2022) Nanoparticle performance for biomedical applications: in vitro / in vivo discrepancies. Biophysics review. doi.org/10.1063/5.0073494..

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