Local minimum in fragility for trehalose/glycerol mixtures: implications for biopharmaceutical stabilization.
Local minimum in fragility for trehalose/glycerol mixtures: implications for biopharmaceutical stabilization.
复制标题
海藻糖/甘油混合物脆性的局部最小值：对生物制药稳定性的影响。
DOI：
10.1021/acs.jpcb.5b01675
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Elliott,GloriaD
中科院分区：
文献类型：
--
作者：
Weng,Lindong;Elliott,GloriaD
大约十年前，观察到向海藻糖中加入少量（5重量%）甘油可以显著改善储存在这些玻璃中的酶的稳定性，即使最终玻璃化转变温度（Tg）降低了1020 K。这一发现激发了人们对脱水海藻糖/甘油混合物的快速动力学的极大兴趣，导致观察到在1.5wt%甘油存在下快速动力学的抑制是最佳的。人们还认识到，理论上，快速动力学应该与这些玻璃形成物的脆性有关，但对于海藻糖/甘油混合物或任何其他这种性质的混合物，缺乏对这一假设的实验证实。采用动态力学分析仪（DMA）测定了海藻糖质量分数为80- 100wt%的海藻糖/甘油混合物的Tg和动力学脆性指数（m）。结果发现，脆性指数与海藻糖的质量分数在一个非单调的方式，与局部最小值之间的87.5和95重量%的海藻糖，而组成依赖性ofTg被发现遵循戈登-泰勒样的关系，没有局部最小值。因此，海藻糖中5- 12.5wt%甘油的组成产生了一种基质，可以最大限度地提高甘油对玻璃形成的贡献，同时最大限度地降低其玻璃化温度效应。这一定量证据支持了过去十年来一直在进行的关于这些混合物的脆弱性特征的推测。本研究开发的DMA-basedTg和脆性测定方法代表了一种新的方法，用于确定最佳组合物的保存生物制品。
Approximately a decade ago it was observed that adding a small amount (5 wt %) of glycerol to trehalose could substantially improve the stability of enzymes stored in these glasses even though the final glass transition temperature (Tg) was reduced by ∼20 K. This finding inspired great interest in the fast dynamics of dehydrated trehalose/glycerol mixtures, leading to the observation that suppression of fast dynamics was optimal in the presence of ∼5 wt % of glycerol. It was also recognized that the fast dynamics should, in theory, be related to the fragility of these glass formers, but experimental confirmation of this hypothesis has been lacking for trehalose/glycerol mixtures or any other mixtures of this nature. In the present study a dynamic mechanical analyzer (DMA) was used to determine both theTgand the kinetic fragility index (m) of trehalose/glycerol mixtures within the mass fraction range of 80–100 wt % of trehalose. It was found that the fragility index correlated with the mass fraction of trehalose in a nonmonotonic manner, with a local minimum between 87.5 and 95 wt % of trehalose, whereas the composition dependence ofTgwas found to follow a Gordon–Taylor-like relationship, with no local minimum. The composition of 5–12.5 wt % glycerol in trehalose thus yielded a matrix that maximized the strong glass-forming contribution of glycerol, while minimizing itsTglowering effect. This quantitative evidence supports speculation about the fragility characteristics of these mixtures that has been ongoing for the past decade. The DMA-basedTgand fragility determination method developed in this study represents a new approach for identifying optimal compositions for preservation of biologics.