Researchers believe that atomic-scale design of pharmaceuticals will be instrumental in producing more accurate and efficient drugs. Computer simulations developed by a team headed by Ravi Radhakrishnan from the University of Pennsylvania will be helpful in optimizing these designs.
Ravi Radhakrishnan
The National Science Foundation’s Division of Chemical, Bioengineering, Environmental & Transport Systems has awarded a ‘Research Highlight’ to the research team for this development. The study results have been reported in the journal, Biophysical Journal.
Nanocarriers are engineered particles capable of holding tiny molecules inside their hollow interiors. Antibodies, which are bonded to the outer surface of these nanocarriers, function as markers to target specific cells or tissues or supply drugs to infected cells without affecting healthy cells. The bonding between these nanocarriers and the targeted tissues must be long enough for efficient drug delivery. Designers hypothesized that larger particles with more amounts of antibodies may bind effectively.
Radhakrishnan’s team devised a versatile model to assess binding under a variety of conditions. The team then populated various simulated conditions with various nanocarrier models by modifying their sizes and antibody quantities to find the optimal arrangement. The comparison between the simulation results and real-life experiments proved that the perception on making more-efficient nanocarriers was wrong.
One of the key findings of the study was that a nanocarrier’s efficacy may actually be reduced by the addition of more antibodies. Radhakrishnan explained that more antibodies result in stronger bonding, thus causing the target tissue receptors to immobilize, which in turn makes them instable. This instability may reduce the chance of delivering drugs.
Another key finding was the nanocarriers can adhere better when the blood flow is stronger. Antibodies are able to identify more binding spots as the flow forces the nanocarriers to roll across the cell surface frequently.
To ensure the simulation results, the team conducted two different physical experiments. First one was an atomic force microscope study to measure the time of popping off of antibody bindings in an in vitro tissue sample. Another one was an in vivo experiment, in which the team used mouse models to study the binding between the nanocarriers and designated targets, and the efficacy of marker. The team achieved high-level of consistency in all three models, thus proving that its findings will be helpful in designing next-generation nanocarriers.
Source: http://www.upenn.edu
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