کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10162563 | 1114334 | 2014 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Modulating Potency: Physicochemical Characteristics are a Determining Factor of TLR4-Agonist Nanosuspension Activity
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کلمات کلیدی
Adjuvant - ادجوانت، یاورEndotoxin - اندوتوکسینVaccine development - توسعه واکسنFTIR - طیف سنج مادون قرمزPhospholipid - فسفولیپیدIn vitro bioactivity - فعالیت زیستی درون in vitroPhysicochemical characterization - مشخصات فیزیکوشیمیاییNanoparticle - نانوذارتToll-like receptors (TLR) - گیرنده های Toll-like (TLR)
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Activity of adjuvanted vaccines is difficult to predict in vitro and in vivo. The wide compositional and conformational range of formulated adjuvants, from aluminum salts to oil-in-water emulsions, makes comparisons between physicochemical and immunological properties difficult. Even within a formulated adjuvant class, excipient selection and concentration can alter potency and physicochemical properties of the mixture. Complete characterization of physicochemical properties of adjuvanted vaccine formulations and relationship to biological response is necessary to move beyond a guess-and-check paradigm toward directed development. Here we present a careful physicochemical characterization of a two-component nanosuspension containing synthetic TLR-4 agonist glucopyranosyl lipid adjuvant (GLA) and 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) at various molar ratios. Physicochemical properties were compared with potency, as measured by stimulation of cytokine production in human whole blood. We found a surprising, nonlinear relationship between physicochemical properties and GLA-DPPC ratios that corresponded well with changes in biological activity. We discuss these data in light of the current understanding of TLR4 activation and the conformation-potency relationship in development of adjuvanted vaccines.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 103, Issue 3, March 2014, Pages 879-889
Journal: Journal of Pharmaceutical Sciences - Volume 103, Issue 3, March 2014, Pages 879-889
نویسندگان
Quinton M. Dowling, Sandra J. Sivananthan, Jeff A. Guderian, Magdalini Moutaftsi, James D. Chesko, Christopher B. Fox, Thomas S. Vedvick, Ryan M. Kramer,