Zeng Xianci, Joshi Pratik U, Lawton Alexander, Manchester Lynn, Heldt Caryn L, Perry Sarah L
Department of Chemical Engineering, University of Massachusetts Amherst, United States.
Department of Chemical Engineering, Michigan Technological University, United States.
J Colloid Interface Sci. 2025 Oct;695:137808. doi: 10.1016/j.jcis.2025.137808. Epub 2025 May 5.
Complex coacervation is an associative liquid-liquid phase separation phenomenon that takes place due to the electrostatic complexation of oppositely-charged polyelectrolytes and the entropic gains associated with the release of bound counterions and rearrangement of solvent. The aqueous nature of coacervation has resulted in its broad use in systems requiring high biocompatibility. The significance of electrostatic interactions in coacervates has meant that studies investigating the phase behaviors of these systems have tended to focus on parameters such as the charge stoichiometry of the polyions, the solution pH, and the ionic strength. However, the equilibrium that exists between the polymer-rich coacervate phase and the polymer-poor supernatant phase represents a balance among attractive electrostatic interactions and excluded volume repulsions as well as osmotic pressure effects. As such, we hypothesize that it should be possible to tune coacervate phase behavior via the addition of non-electrostatic excipients which would partition between the two phases and potentially alter both the solvent quality and the osmotic pressure balance. In particular, our work focuses on small molecule excipients such as sugars, amino acids, and other additives that have a history of use in vaccine formulation. We quantified the ability of these excipients to partition into the coacervate phase, and their potential for destabilizing the phase separation. Furthermore, we demonstrate that these additives can be combined with complex coacervation in the context of a virus formulation.
复合凝聚是一种缔合性液-液相分离现象，它是由于带相反电荷的聚电解质之间的静电络合作用以及与结合抗衡离子的释放和溶剂重排相关的熵增而发生的。凝聚的水性使其在需要高生物相容性的系统中得到广泛应用。凝聚相中静电相互作用的重要性意味着，研究这些系统相行为的研究往往集中在诸如聚离子的电荷化学计量、溶液pH值和离子强度等参数上。然而，富含聚合物的凝聚相和贫聚合物的上清液相之间存在的平衡代表了有吸引力的静电相互作用、排除体积排斥以及渗透压效应之间的平衡。因此，我们假设通过添加非静电赋形剂来调节凝聚相行为应该是可行的，这些赋形剂会在两相之间分配，并可能改变溶剂性质和渗透压平衡。特别是，我们的工作集中在小分子赋形剂上，如糖、氨基酸和其他在疫苗配方中有使用历史的添加剂。我们量化了这些赋形剂分配到凝聚相中的能力，以及它们破坏相分离的可能性。此外，我们证明了这些添加剂可以在病毒配方的背景下与复合凝聚相结合。
