标题： 糖依赖性聚合物稳定性的热力学基础：指导生物制剂配方设计 显示英文标题

标题： Thermodynamic Basis of Sugar-Dependent Polymer Stabilization: Informing Biologic Formulation Design

摘要： 大分子的稳定对于开发生物制剂，如疫苗和蛋白质治疗药物是基本的。 在本研究中，我们采用粗粒度聚合物模型来研究四种糖： {\alpha }-葡萄糖，{\beta }-果糖，海藻糖和蔗糖对大分子稳定性的影响。 自由能分解和优先相互作用分析表明，聚合物-糖相互作用在低浓度时有利于折叠，而在较高浓度时则导致展开。 相反，在研究的所有糖浓度下，聚合物-溶剂的软相互作用熵始终有利于展开。 在低糖浓度下，聚合物-溶剂相互作用主要支配稳定，而在较高浓度下，熵罚决定了聚合物的稳定性。 局部混合熵表明，二元糖混合物引入了优先稳定折叠状态的熵贡献。 这些发现有助于更深入地理解基于糖的赋形剂稳定机制，为稳定生物制剂的合理设计提供指导。 显示英文摘要

摘要： The stabilization of macromolecules is fundamental to developing biological formulations, such as vaccines and protein therapeutics. In this study, we employ coarse grained polymer models to investigate the impact of four sugars: {\alpha}-glucose, {\beta}-fructose, trehalose, and sucrose on macromolecule stability. Free energy decomposition and preferential interaction analysis indicate that polymer-sugar interactions favor folding at low concentrations while driving unfolding at higher concentrations. In contrast, the polymer-solvent soft interaction entropy consistently favors unfolding across all sugar concentrations under study. At low sugar concentrations, polymer-solvent interactions predominantly govern stabilization, whereas at higher concentrations, entropic penalties dictate polymer stability. Local mixing entropy demonstrates that binary sugar mixtures introduce entropic contributions that preferentially stabilize the folded state. These findings contribute to a more nuanced understanding of sugar-based excipient stabilization mechanisms, offering guidance for the rational design of stable biological formulations.