کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485322 | 1114352 | 2008 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Physical Stabilization of Norwalk VirusâLike Particles*
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کلمات کلیدی
protein aggregation - تجمع پروتئینPhysical stability - ثبات فیزیکیcircular dichroism - رنگ تابی دورانیExcipients - عضلاتProtein formulation - فرمول پروتئینFluorescence spectroscopy - فوتولومینسانس یا فلوئورسانس یا فسفرسانسVaccines - واکسنPreformulation - پیش فرآیندCalorimetry (DSC) - کالریمتری (DSC)
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Virusâlike particles (VLPs) used as vaccine antigens often elicit strong immune responses due to their intrinsic repetitive, highâdensity display of epitopes, and the fact that the mammalian immune system is highly attuned to recognizing particles in the size range of viruses (20-150 nm). To retain these immunogenic qualities, vaccines that utilize virusâlike particle (VLP) antigens should be formulated to stabilize both native conformational epitopes and the overall particulate nature of the VLP. This work describes a systematic approach for identifying potential stabilizers for formulation of Norwalk VLPs (NVâVLPs) in aqueous suspension. A number of excipients were screened for their ability to inhibit aggregation of NVâVLPs under conditions known to induce aggregation. Those compounds shown to inhibit aggregation were further evaluated under conditions of thermal stress and the NVâVLP structure was monitored using biophysical techniques such as CD, ANS fluorescence, and DSC to provide insight into the mechanisms by which stability was conferred. Increased thermal stability in the presence of chitosan glutamate, sucrose, and trehalose was correlated with stabilization of secondary and tertiary structural elements of NVâVLPs. These excipients may be useful for formulation of a stable NVâVLP vaccine. © 2008 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 97:4208-4218, 2008
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 10, October 2008, Pages 4208-4218
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 10, October 2008, Pages 4208-4218
نویسندگان
Julian Kissmann, Salvador F. Ausar, Thomas R. Foubert, Julie Brock, Mary H. Switzer, Edward J. Detzi, Thomas S. Vedvick, C.Russell Middaugh,