Antibody-based drugs often become too thick to be injected at high concentrations. Now, new research can explain why this happens—knowledge that could eventually lead to easily injectable medications.
Antibody-based drugs are currently used to treat cancer, autoimmune diseases, and inflammatory conditions. To be administered as a simple injection under the skin, they need to be concentrated, but at high concentrations, they often become too thick to handle. This affects both how accessible a treatment is, as well as the patient’s discomfort.
By using advanced computer simulations, the researchers were able to show that the increased viscosity (a term describing how easily or thickly a substance flows) is due to antibodies in concentrated solutions forming short-lived, strongly charge-driven structures. These temporary formations cause the solution to "thicken."
"We were surprised that models previously used to describe the structure of antibody solutions couldn't predict these dynamics. It's clear that electrical charges play a crucial role in understanding the true properties," explains Fabrizio Camerin, chemistry researcher at Lund University.
Unlike more basic models, the study shows that one must consider both the complex charge distribution of the antibodies and the surrounding ions in the solution, to accurately reproduce experimental results.
The findings pave the way for new methods of predicting how different antibodies will behave at high concentrations. This could provide valuable guidance for pharmaceutical companies in creating formulations that remain stable yet easy to inject.
"By understanding the mechanism behind viscous antibody solutions, we can contribute to better treatment strategies and improved quality of life for patients," concludes Fabrizio Camerin.
Proceedings of the National Academy of Sciences
Electrostatics and viscosity are strongly linked in concentrated antibody solutions