کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486473 | 1114384 | 2010 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Equilibrium studies of protein aggregates and homogeneous nucleation in protein formulation
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کلمات کلیدی
IgGMechanical stress - استرس مکانیکیHeat stress - استرس گرماییSpiking - اسپایکینگprotein aggregation - تجمع پروتئینSoluble aggregates - ترکیبات قابل حلShaking - تکان دادنDenaturation - دناتوره شدن، دناتوراسیون، واسرشتنLight obscuration - نور مضرNucleation - هستهDynamic Light Scattering - پراکندگی نور دینامیکیSeeding - کاشتSize exclusion chromatography - کروماتوگرافی اندازهای طردیTurbidity - کمبود
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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چکیده انگلیسی
Shaking or heat stress may induce protein aggregates. Aggregation behavior of an IgG1 stressed by shaking or heat following static storage at 5 and 25°C was investigated to determine whether protein aggregates exist in equilibrium. Aggregates were detected using different analytical methods including visual inspection, turbidity, light obscuration, size exclusion chromatography, and dynamic light scattering. Significant differences were evident between shaken and heated samples upon storage. Visible and subvisible particles (insoluble aggregates), turbidity and z-average diameter decreased whilst soluble aggregate content increased in shaken samples over time. Insoluble aggregates were considered to be reversible and dissociate into soluble aggregates and both aggregate types existed in equilibrium. Heat-induced aggregates had a denatured protein structure and upon static storage, no significant change in insoluble aggregates content was shown, whilst changes in soluble aggregates content occurred. This suggested that heat-induced insoluble aggregates were irreversible and not in equilibrium with soluble aggregates. Additionally, the aggregation behavior of unstressed IgG1 after spiking with heavily aggregated material (shaken or heat stressed) was studied. The aggregation behavior was not significantly altered, independent of the spiking concentration over time. Thus, neither mechanically stressed native nor temperature-induced denatured aggregates were involved in nucleating or propagating aggregation. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:632-644, 2010
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 2, February 2010, Pages 632-644
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 2, February 2010, Pages 632-644
نویسندگان
Sylvia Kiese, Astrid Pappenberger, Wolfgang Friess, Hanns-Christian Mahler,