Lewis Conor M, Heise Charles T, Harasimiuk Natalia, Tovey Jennifer, Lu Jian R, Waigh Thomas A
Biological Physics, Department of Physics and Astronomy, University of Manchester, Manchester M13 9PL, United Kingdom.
FUJIFILM Diosynth Biotechnolgies, Billingham TS23 1LH, United Kingdom.
APL Bioeng. 2024 Apr 24;8(2):026105. doi: 10.1063/5.0201626. eCollection 2024 Jun.
The viscoelasticity of monoclonal antibodies (mAbs) is important during their production, formulation, and drug delivery. High concentration mAbs can provide higher efficacy therapeutics (e.g., during immunotherapy) and improved efficiency during their production (economy of scale during processing). Two humanized mAbs were studied (mAb-1 and mAb-2) with differing isoelectric points. Using high speed particle tracking microrheology, we demonstrated that the mAb solutions have significant viscoelasticities above concentrations of 40 mg/ml. Power law viscoelasticity was observed over the range of time scales (-1 s) probed for the high concentration mAb suspensions. The terminal viscosity demonstrated an exponential dependence on mAb concentration (a modified Mooney relationship) as expected for charged stabilized Brownian colloids. Gelation of the mAbs was explored by lowering the pH of the buffer and a power law scaling of the gelation transition was observed, i.e., the exponent of the anomalous diffusion of the probe particles scaled inversely with the gelation time.
单克隆抗体（mAb）的粘弹性在其生产、制剂和药物递送过程中至关重要。高浓度的单克隆抗体可提供更高疗效的治疗方法（例如在免疫治疗期间），并在其生产过程中提高效率（加工过程中的规模经济）。研究了两种具有不同等电点的人源化单克隆抗体（mAb-1和mAb-2）。使用高速粒子跟踪微流变学，我们证明了单克隆抗体溶液在浓度高于40 mg/ml时具有显著的粘弹性。在探测的高浓度单克隆抗体悬浮液的时间尺度范围内（-1 s）观察到幂律粘弹性。如带电稳定的布朗胶体所预期的那样，终端粘度表现出对单克隆抗体浓度的指数依赖性（修正的穆尼关系）。通过降低缓冲液的pH值来探索单克隆抗体的凝胶化，并观察到凝胶化转变的幂律标度，即探针颗粒异常扩散的指数与凝胶化时间成反比。
