【摘 要】
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Polymer based delivery systems enable controlled delivery of proteins and an emerging aspect of which is use of nano-particulate polymers for intravenous administration.Evaluation of structural change
【机 构】
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Pharmaceutical Development The Medicines Company USA
【出 处】
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中国上海第七届国际新药发明科技年会
论文部分内容阅读
Polymer based delivery systems enable controlled delivery of proteins and an emerging aspect of which is use of nano-particulate polymers for intravenous administration.Evaluation of structural changes of the adsorbed protein on the polymer surface will help understand the nature of the interactions that govern the adsorption of the protein on the polymer,leading to successful design of nano-particulate delivery systems.While micro-calorimetric analysis provides information of the energetics and the thermodynamic basis,circular dichroism (CD) spectroscopy provides secondary and tertiary structural information.Hence,combinations of both techniques were applied to study the structural changes of recombinant human growth hormone (r-hGH) adsorbed onto ultra-fine positively and negatively charged polystyrene particles.The r-hGH covered polystyrene particles were prepared by mixing appropriate concentrations of r-hGH and the polymer based on previously determined adsorption isotherms.While micro-calorimetric analysis was performed under all the desired conditions,CD could be done only under conditions where the colloidal stability of the polymer was not affected as a result of r-hGH adsorption.These studies revealed that adsorption of r-hGH onto polystyrene nano-particles involved substantial changes in secondary structure when compared to that in its native state,suggesting contribution from structural rearrangements to the overall adsorption process.
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