School of Mechanical Engineering, Purdue University, West Lafayette, Indiana 47906, United States.
Mol Pharm. 2021 Dec 6;18(12):4385-4392. doi: 10.1021/acs.molpharmaceut.1c00561. Epub 2021 Oct 26.
Concentrated monoclonal antibody solutions exhibit high solution viscosity, which is experimentally measured to be ∼1-2 orders of magnitude higher than the viscosity of water. However, physical processes responsible for the high antibody viscosity are not fully understood. We show that fluid occlusion due to the trapped solvent molecules within the boundaries formed by the aggregated antibodies is responsible for the elevated solution viscosity. We develop a theory to predict the viscosity of monoclonal antibodies based on the geometry of the antibody molecule and the aggregate morphology. We validate our theory with experiments and highlight useful insights obtained from the viscosity equation which could help in controlling the drug viscosity at the molecular design stage itself.
浓缩单克隆抗体溶液表现出高溶液黏度，实验测量其黏度比水的黏度高约 1-2 个数量级。然而，导致抗体高黏度的物理过程尚未完全理解。我们表明，由于被截留的溶剂分子被困在由聚集的抗体形成的边界内，导致溶液黏度升高。我们提出了一种基于抗体分子的几何形状和聚集形态来预测单克隆抗体黏度的理论。我们通过实验验证了我们的理论，并强调了从黏度方程中获得的有用见解，这些见解可以帮助在分子设计阶段控制药物黏度。
