Polypseudorotaxane-based supramolecular hydrogels consisting of cyclodextrins and Pluronics as stabilizing agents for antibody drugs
Polypseudorotaxane-based supramolecular hydrogels consisting of cyclodextrins and Pluronics as stabilizing agents for antibody drugs
复制标题
DOI：
10.1016/j.carbpol.2020.117419
复制
发表时间：
2021-01-19
影响因子：
11.2
通讯作者：
Higashi, Taishi
中科院分区：
文献类型：
--
作者：
Ohshita, Naoko;Motoyama, Keiichi;Higashi, Taishi
最近，抗体药物在全球范围内得到应用，基于全球销售额，2019年前10大医药产品中有7个是抗体药物。然而，抗体药物通常在热应力和振荡应力下形成聚集体，几乎没有有效的稳定剂对抗这两种应力。本文中，我们开发了由环糊精（CyD）和聚乙二醇（PEG）-聚丙二醇（PPG）-PEG嵌段共聚物（Pluronics F108、F87、F68和L44）组成的聚紫杉醇（PpRX）水凝胶，并评估了它们作为抗体稳定剂的效用。α和γ-CyD与Pluronics形成PpRX水凝胶，其中CyD/F108凝胶显示出对人免疫球蛋白G（IgG）抵抗热应力和摇动应力的显著稳定作用，超过CyD/PEG凝胶或通用凝胶。这些影响可能是由于IgG与Pluronic F108的游离PPG阻断剂之间的相互作用，导致IgG在凝胶中的强保留。这些发现表明CyD/Pluronic凝胶作为抗体制剂的药物材料的巨大潜力。
Recently, antibody drugs have been used worldwide, and based on worldwide sales, 7 of the top 10 pharmaceutical products in 2019 were antibody-based drugs. However, antibody drugs often form aggregates upon thermal and shaking stresses with few efficient stabilizing agents against both stresses. Herein, we developed polypseudorotaxane (PpRX) hydrogels consisting of cyclodextrins (CyDs) and polyethylene glycol (PEG)-polypropylene glycol (PPG)-PEG block copolymers (Pluronics F108, F87, F68, and L44), and evaluated their utility as antibody stabilizing agents. alpha and gamma-CyDs formed PpRX hydrogels with Pluronics, where CyD/F108 gels showed remarkable stabilizing effects for human immunoglobulin G (IgG) against both thermal and shaking stresses beyond CyD/PEG gels or generic gels. The effects were probably due to the interaction between IgG and the free PPG block of Pluronic F108, resulting in the strong IgG retention in the gels. These findings suggest the great potential of CyD/Pluronic gels as pharmaceutical materials for antibody formulations.