More predictive in vitro assays may improve nanomedicine
Protein corona formation information exploited to optimize carriers for nanomedical applications
Date:
February 1, 2022
Source:
American Institute of Physics
Summary:
One recent obstacle to drug delivery research is an observed
weak correlation between in vitro and in vivo performance. When
nanoparticles are applied intravenously, they face several
obstacles that differ from in vitro situations. Nanoparticles are
usually covered by a biomolecular multilayer (a protein corona),
which alters the physiochemical properties, pharmacokinetics,
and toxicity profile of the nanoparticles.
FULL STORY ========================================================================== Messenger RNA (mRNA) vaccines are a prime example of the promising
field of nanomedicine. But progress in the design and application
of nanoparticles as efficient delivery vehicles for biopharmaceutics
containing nucleic acid or protein drug substances is, unfortunately, remarkably slow.
==========================================================================
One recent obstacle to drug delivery research is an observed weak
correlation between in vitro (outside a living organism) and in
vivo(inside a living organism) performance. This problem was not clear
in early stages, when cellular delivery of a drug nanocarrier was tested primarily within standard cell culture. With advanced pharmacological
in vivo studies emerging in mice or human patients, the low reliability
and validity of cell culture testing for therapeutic applications is
becoming apparent.
When nanoparticles are applied intravenously, they face several obstacles
that differ from in vitro situations, such as when they meet blood
components.
Nanoparticles are usually covered by a biomolecular multilayer (a protein corona), which alters the physiochemical properties, pharmacokinetics,
and toxicity profile of the nanoparticles.
In Biophysics Reviews, from AIP Publishing, researchers in Germany
provide a cutting-edge characterization of the protein corona formed
around nanoparticles and its impact on the physiochemical and biological properties of these nanoparticles.
"When predicting in vivoperformance from in vitro data, it is recommended
to combine several analytical and biological characterization methods to
get more detailed insight into the in vivo characteristics and behavior
of the nanoparticles," said Simone Berger, a co-author from Ludwig
Maximilian University of Munich.
The choice of the biofluid -- serum, plasma, or full blood, and
animal in origin -- and establishment of standardized protocols are
of great importance for more consistent, robust, and comprehensive preclinicalstudies to derive structure-activity relationships and in
vitro/in vivocorrelations.
"The knowledge gained about protein corona formation can be exploited
to optimize carriers for nanomedical application," Berger said.
Information like 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 barcoding system can
make in vivoinvestigations more effective, economical, and ethical.
Some uncertainty remains about translatability from small to large animals
and humans, but bioinformatics could help identify best-fitting animal
models for certain diseases.
"Alternatives to animal models, such as microfluidic
'human-organ-on-a-chip' technology or computational predictions, may
be promising strategies for replacing animal studies in the future,"
Berger said.
Nanomedicine shows "great potential to revolutionize the
therapeutic landscape with a broad range of applications like
cancer vaccines/immunotherapy or treatment of genetic disorders,"
said Berger. "With proper and more predictive in vitro assays, the
preclinical pipeline will become more efficient, faster, and economic. And importantly, animal experiments can be replaced or at least reduced." ========================================================================== Story Source: Materials provided by American_Institute_of_Physics. Note: Content may be edited for style and length.
========================================================================== Journal Reference:
1. Simone Berger, Martin Berger, Christoph Bantz, Michael Maskos, Ernst
Wagner. Performance of nanoparticles for biomedical applications:
The in vitro/in vivo discrepancy. Biophysics Reviews, 2022; 3 (1):
011303 DOI: 10.1063/5.0073494 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/02/220201115259.htm
--- up 8 weeks, 3 days, 7 hours, 13 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)