Polysorbates (PSs) are common protein stabilizers used in biotherapeutic formulations. However, PSs are heterogeneous and unstable in liquid protein formulations [1,2]. The purpose of this work is to explore possible alternatives for polysorbate replacements that demonstrate superior protein protection, superior self-stability, low toxicity, and wide applicability. For this purpose, 8 non-ionic surfactants that have not yet been used as excipients in marketed biotherapeutic products were investigated with PS20/80 as the benchmark. Compared with PS20/80, Brij-58 showed better protein protection ability in the mAb1 formulation under forced degradation conditions when examined by visual inspection, SEC, and dynamic lighting scanning. Additionally, Brij-58 has a better inherent stability than PS20/80 in the protein formulation when detected by UPLC-CAD. Moreover, Brij-58 is an inert excipient that does not affect protein bioactivity and conformation. In addition, the LD50 and hemolysis concentration of Brij-58 were determined, which is relatively safe when used as a parenteral injection. Furthermore, Brij-58 was also an effective protein stabilizer for the other two antibody products (IgG4 subtype and bispecific antibody) in the shaking study. In summary, Brij-58 stands out as a promising PS replacement in biotherapeutic formulations with a safe, stable and effective protein-protection profile among candidate surfactants.

中文翻译：

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Brij-58，一种潜在的可注射蛋白质稳定剂，用于治疗性蛋白质制剂。

聚山梨酯（PSs）是生物治疗制剂中常用的蛋白质稳定剂。然而，PS在液体蛋白制剂中是异质的，并且不稳定[1,2]。这项工作的目的是探索聚山梨酯替代品的可能替代品，这些替代品具有出色的蛋白质保护，出色的自我稳定性，低毒性和广泛的适用性。为此，以PS20 / 80为基准，研究了8种尚未在市售生物治疗产品中用作赋形剂的非离子表面活性剂。与PS20 / 80相比，Brij-58在通过目视检查，SEC和动态照明扫描进行检查时，在强制降解条件下的mAb1制剂中显示出更好的蛋白质保护能力。此外，当通过UPLC-CAD检测时，Brij-58在蛋白质制剂中具有比PS20 / 80更好的固有稳定性。此外，Brij-58是一种惰性赋形剂，不影响蛋白质的生物活性和构象。另外，测定了Brij-58的LD50和溶血浓度，当用作肠胃外注射剂时是相对安全的。此外，在摇动研究中，Brij-58还是其他两种抗体产品（IgG4亚型和双特异性抗体）的有效蛋白质稳定剂。综上所述，Brij-58在生物治疗制剂中以其安全，稳定和有效的蛋白质保护特性在候选表面活性剂中脱颖而出，成为有前途的PS替代品。测定了Brij-58的LD50和溶血浓度，当用于肠胃外注射时相对安全。此外，在摇动研究中，Brij-58还是其他两种抗体产品（IgG4亚型和双特异性抗体）的有效蛋白质稳定剂。综上所述，Brij-58在生物治疗制剂中以其安全，稳定和有效的蛋白质保护特性在候选表面活性剂中脱颖而出，成为有前途的PS替代品。测定了Brij-58的LD50和溶血浓度，当用于肠胃外注射时相对安全。此外，在摇动研究中，Brij-58还是其他两种抗体产品（IgG4亚型和双特异性抗体）的有效蛋白质稳定剂。综上所述，Brij-58在生物治疗制剂中以其安全，稳定和有效的蛋白质保护特性在候选表面活性剂中脱颖而出，成为有前途的PS替代品。