کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5521322 1545303 2017 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research paperElucidating the weak protein-protein interaction mechanisms behind the liquid-liquid phase separation of a mAb solution by different types of additives
ترجمه فارسی عنوان
تعریف مکانیسم های متصل کننده پروتئین و پروتئین ضعیف در جداسازی فاز مایع محلول مونوب با انواع افزودنی های مختلف
کلمات کلیدی
انتی بادی مونوکلونال، جداسازی فاز مایع مایع، پارامتر تعامل، نمودار فاز، غلظت بالا پروتئین، پایداری پروتئین،
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
چکیده انگلیسی

Liquid-liquid phase separation (LLPS) has long been observed during the physical stability investigation of therapeutic protein formulations. The buffer conditions and the presence of various excipients are thought to play important roles in the formulation development of monoclonal antibodies (mAbs). In this study, the effects of several small-molecule excipients (histidine, alanine, glycine, sodium phosphate, sodium chloride, sorbitol and sucrose) with diverse physical-chemical properties on LLPS of a model IgG1 (JM2) solutions were investigated by multiple techniques, including UV-vis spectroscopy, circular dichroism, differential scanning calorimetry/fluorimetry, size exclusion chromatography and dynamic light scattering. The LLPS of JM2 was confirmed to be a thermodynamic equilibrium process with no structural changes or irreversible aggregation of proteins. Phase diagrams of various JM2 formulations were constructed, suggesting that the phase behavior of JM2 was dependent on the solution pH, ionic strength and the presence of other excipients such as glycine, alanine, sorbitol and sucrose. Furthermore, we demonstrated that for this mAb, the interaction parameter (kD) determined at low protein concentration appeared to be a good predictor for the occurrence of LLPS at high concentration.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 120, November 2017, Pages 1-8
نویسندگان
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