Examining Interactions at the Air-Water Interface to Protect Fragile Therapeutics – Dr. Raymond Tu and Charles Maldarelli

by Gabriel Rivera

CCNY Department of Chemical Engineering Professors Raymond Tu and Charles Maldarelli’s research on the role of the air-water interface in the production and storage of new protein-based therapeutics, particularly monoclonal antibodies, was published in an article in Science Advances.

The two chemical engineers and their Ph.D. student, Ankit Kanthe, partnered with Bristol Myers Squibb, a global pharmaceutical company, and Argonne National Labs to work on the project.

They tested monoclonal antibodies – the “target” of many of today’s new pharmaceutical drugs – and how the molecule interacts with the air-water interface.

https://www.ccny.cuny.edu/profiles/charles-maldarelli

“[Bristol Myers Squibb] had originally outlined the issues with the absorption of these monoclonal antibodies to air-water surfaces, where the adsorption of molecules led to a reduction in the target dosage,” Dr. Maldarelli said.

“And so what they wanted was a fundamental study of the absorption of these antibodies to the air-water surface and how this absorption could be prevented by using excipients, which are other surface-active molecules.”

Over the last decade, therapeutics has shifted from drugs comprised of small molecules to drugs larger and more fragile, according to Dr. Tu.

With therapeutics growing more complex by the decade, they can unfold and precipitate during manufacture, purification, and storage.

“For example, the newer COVID vaccines from Pfizer and Moderna are an mRNA drug, so it’s this big molecule that doesn’t have a molecular weight of hundreds, it has a molecular weight of thousands or hundreds of thousands,” Dr. Tu said. “It’s much bigger and these molecules, people have come to know, require special formulations and storage conditions.”

Between laboratories at CCNY and Argonne National Laboratories, a multidisciplinary science and engineering research center in Chicago, Illinois, the team conducted their research and collected x-ray reflectivity measurements to gain a better understanding of the absorption process of monoclonal antibodies at the air-water interface, which could, in turn, improve the production of monoclonal antibody-based therapeutics.

Dr. Raymond Tu

https://www.ccny.cuny.edu/profiles/raymond-tu

“The business of doing x-ray studies at Argonne requires three or four days of really alert experimental work where you’re up for 24 hours a day using every x-ray that you can, but then the months-long process of analysis and modeling is really where the investment of time is needed to understand the fundamental molecular behavior of these molecules adsorbing to interfaces,” Dr. Tu said.

Their findings in the journal article are the culmination of four years of traveling between West Harlem and Chicago to conduct experiments on monoclonal antibodies and were made possible by the diverse range of expertise Dr. Tu and Dr. Maldarelli brought to the project.

From their tireless work with the molecule and its interaction with the air-water interface, Dr. Tu and Dr. Maldarelli’s team found monoclonal antibodies could be protected from the absorption process that occurs at the air-water interface with the addition of surfactants.

With a greater understanding of how to prevent absorption of monoclonal antibodies, Dr. Tu and Dr. Maldarelli hope it will lead to more discussion and experimentation on how other larger and more fragile molecules can be formulated to make these new medicines more accessible.

“Our goal is to understand the process of adsorption where adding surfactants in with the monoclonal antibodies can allow for easier processing and longer storage,” Dr. Tu said.

“In addition to that, understanding what happens as those molecules absorb to the interface, how they’re oriented and even perhaps how they begin to unfold once they get to that surface — those are broader questions that the scientific community will certainly care about.”

For now, the team hopes that Bristol Myers Squibb and other pharmaceutical manufacturers will use their findings to improve the production and efficacy of their drugs by determining which surfactant concentration works best with monoclonal antibodies to ensure the air-water interface is protected.

Future plans involve verifying the predictions of the models they published to make them more quantitative. But both hope to expand on this research and examine the absorption of other biomacromolecules at the air-water surface with a broader lens to discover what occurs at the molecular level.

“I think we’d like to do more with molecular simulations and build on the insight you can get from molecular simulations with experiments, especially the type of experiments we did at Argonne with x-ray reflectivity where we can tell what orientations the molecules take by comparing the results of the experiment with more detailed molecular studies of the interfacial configuration,” Dr. Maldarelli said.

And outside of the scientific findings, both Dr. Tu and Dr. Maldarelli both enjoyed the experience of working with Bristol Myers Squibb, which allowed them to frame their research around a critical industrial problem.

“Working with industry is invaluable for the student and for the professors. I think it elevates their research and makes them think about things that are sometimes complex, multi-component systems but are necessary, and everybody benefits in the end,” Dr. Maldarelli said.

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