Silicone oil- and agitation-induced aggregation of a monoclonal antibody in aqueous solution.
Silicone oil- and agitation-induced aggregation of a monoclonal antibody in aqueous solution.
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DOI：
10.1002/jps.21719
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发表时间：
2009-09
影响因子：
3.8
通讯作者：
Carpenter, John F.
中科院分区：
文献类型：
--
作者：
Thirumangalathu, Renuka;Krishnan, Sampathkumar;Ricci, Margaret Speed;Brems, David N.;Randolph, Theodore W.;Carpenter, John F.
硅油用作注射器、针头和药物容器等设备中的润滑剂或涂层，与蛋白质和抗体的聚集和颗粒化有关。硅油引起的治疗性蛋白质产品的聚集可能对其开发和商业化构成挑战。为了系统地表征硅油对蛋白质聚集的作用，检查了搅拌、温度、pH 和离子强度对硅油诱导的单体抗链霉亲和素 IgG 1 抗体损失的影响。此外，还研究了赋形剂聚山梨酯20和蔗糖对蛋白质聚集的影响。在没有搅拌的情况下，蛋白质被吸收到硅油上并具有大约单层覆盖，但是硅油在等温孵育期间不会刺激聚集，除非样品也被搅拌。观察到搅拌和硅油的组合对聚集的协同刺激。通过测定渗透第二维里系数评估，降低抗体胶体稳定性的溶液条件加速了硅油搅拌期间的聚集。聚山梨酯 20 完全抑制搅拌过程中硅油引起的单体损失。提出了优化抗体胶体稳定性以及掺入聚山梨酯20等表面活性剂的配方策略，以减少硅油诱导的治疗性蛋白质产品聚集。
Silicone oil, which is used as a lubricant or coating in devices such as syringes, needles and pharmaceutical containers, has been implicated in aggregation and particulation of proteins and antibodies. Aggregation of therapeutic protein products induced by silicone oil can pose a challenge to their development and commercialization. To systematically characterize the role of silicone oil on protein aggregation, the effects of agitation, temperature, pH and ionic strength on silicone oil-induced loss of monomeric anti-streptavidin IgG 1 antibody were examined. Additionally, the influences of excipients polysorbate20 and sucrose on protein aggregation were investigated. In the absence of agitation, protein absorbed to silicone oil with approximately monolayer coverage, however silicone oil did not stimulate aggregation during isothermal incubation unless samples were also agitated. A synergistic stimulation of aggregation by a combination of agitation and silicone oil was observed. Solution conditions which reduced colloidal stability of the antibody, as assessed by determination of osmotic second virial coefficients, accelerated aggregation during agitation with silicone oil. Polysorbate20 completely inhibited silicone oil-induced monomer loss during agitation. A formulation strategy optimizing colloidal stability of the antibody as well as incorporation of surfactants such as polysorbate20 is proposed to reduce silicone oil-induced aggregation of therapeutic protein products.
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影响因子：
3.5
作者：
BALDWIN, RN
通讯作者：
BALDWIN, RN
影响因子：
46.9
作者：
Reichert, JM;Rosensweig, CJ;Dewitz, MC
通讯作者：
Dewitz, MC
影响因子：
3.8
作者：
Bam, NB;Cleland, JL;Randolph, JW
通讯作者：
Randolph, JW
影响因子：
2.9
作者：
Krishnan, S;Chi, EY;Carpenter, JF
通讯作者：
Carpenter, JF
DOI：
10.1107/s0907444994001216
发表时间：
1994-07-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
GEORGE, A;WILSON, WW
通讯作者：
WILSON, WW