421 Washington Ave SE, Minneapolis, MN 55455, USA.
Soft Matter. 2021 Nov 3;17(42):9624-9635. doi: 10.1039/d1sm01253c.
Limited studies measure extensional rheology in protein solutions due to volume constraints and measurement challenges. We developed a small-volume, dripping-onto-substrate (DoS) extensional rheology device to measure the capillary thinning of protein and protein-excipient solutions DoS for the first time. Ovalbumin (OVA) was used as a model system, examined DoS both with and without excipient poloxamer 188 (P188). Water and dilute OVA break apart rapidly and demonstrate inertiocapillary (IC) thinning behavior, where longer breakup times in OVA can be attributed to lower surface tension. Further increasing OVA content leads to longer breakup times and deviations from IC thinning at the start of thinning, however, no evidence of elastic behavior is observed. P188 more effectively lowers the droplet surface tension than OVA, transitioning from IC behavior in dilute solution to weakly elastic behavior at higher concentrations. Combined protein/excipient formulations act synergistically at low concentrations, where breakup times are identical to those of the individual components despite the higher total concentration. However concentrated protein/excipient formulations exhibit elasticity, where extensional rheology parameters depend on P188 content and total concentration. These findings imply that excipients intended to stabilize proteins in shear flow can cause undesirable behavior in extensional flows like injection.
由于体积限制和测量挑战，有限的研究测量蛋白质溶液的拉伸流变学。我们开发了一种小体积、滴落到基底上（DoS）的拉伸流变仪，首次用于测量蛋白质和蛋白质-赋形剂溶液的毛细变薄。卵清蛋白（OVA）被用作模型系统，分别考察了 DoS 有无赋形剂泊洛沙姆 188（P188）的情况。水和稀 OVA 迅速分解，表现出惯性毛细（IC）变薄行为，其中较长的 OVA 断裂时间归因于较低的表面张力。进一步增加 OVA 的含量会导致更长的断裂时间和在变薄开始时偏离 IC 变薄，但没有观察到弹性行为的证据。P188 比 OVA 更有效地降低液滴的表面张力，从稀溶液中的 IC 行为转变为较高浓度下的弱弹性行为。结合蛋白质/赋形剂配方在低浓度下协同作用，尽管总浓度较高，但断裂时间与单个成分的断裂时间相同。然而，浓缩的蛋白质/赋形剂配方表现出弹性，其中拉伸流变学参数取决于 P188 的含量和总浓度。这些发现意味着旨在稳定蛋白质剪切流中的赋形剂可能会导致注射等拉伸流中不期望的行为。
