Label-Free Measurements of Tenofovir Diffusion Coefficients in a Microbicide Gel Using Raman Spectroscopy
Label-Free Measurements of Tenofovir Diffusion Coefficients in a Microbicide Gel Using Raman Spectroscopy
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DOI：
10.1016/j.xphs.2016.09.030
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发表时间：
2017-02-01
影响因子：
3.8
通讯作者：
Katz, David F.
中科院分区：
文献类型：
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作者：
Chuchuen, Oranat;Maher, Jason R.;Katz, David F.
共焦拉曼光谱实施了一种新的无标记技术，以量化凝胶内的分子扩散系数。一种主要的抗艾滋病毒药物，替诺福韦，在临床杀微生物剂凝胶中进行了分析。测试未稀释的凝胶，以及用阴道液模拟物以10%-50%wt/wt稀释的凝胶，以捕获体内可能发生的条件范围。测定替诺福韦在凝胶中的浓度随时间和空间的分布，并将其输入数学扩散模型以推导扩散系数。在未稀释的凝胶中，这些值为3.16 +/- 0.11 x 10（-6）cm（2）/s，并根据稀释程度增加11%-46%。结果解释与传统的释放速率测量装置，如Franz细胞。这种比较突出了我们的测定的优点，因为它表征了凝胶材料本身内的扩散屏障;相反，传统测定中的释放速率受外部条件的影响，例如凝胶/液体槽界面处的药物分配。这种新的测定方法与聚合物水凝胶中的扩散相关，例如，局部药物递送的特征。所得的传输参数是药物递送潜力的显著量度，并且用作药物递送性能的计算模型的输入。(C)2017年美国药学协会（R）。爱思唯尔公司出版All rights reserved.
Confocal Raman spectroscopy was implemented in a new label-free technique to quantify molecular diffusion coefficients within gels. A leading anti-HIV drug, tenofovir, was analyzed in a clinical microbicide gel. The gel was tested undiluted, and in 10%-50% wt/wt dilutions with vaginal fluid simulant to capture the range of conditions likely occurring in vivo. The concentration distributions of tenofovir in gel over time and space were measured and input to a mathematical diffusion model to deduce diffusion coefficients. These were 3.16 +/- 0.11 x 10(-6) cm(2)/s in undiluted gel, and increased by 11%-46% depending on the extent of dilution. Results were interpreted with respect to traditional release rate measurements in devices such as Franz cells. This comparison highlighted an advantage of our assay in that it characterizes the diffusive barrier within the gel material itself; in contrast, release rate in the traditional assay is affected by external conditions, such as drug partitioning at the gel/liquid sink interface. This new assay is relevant to diffusion in polymeric hydrogels over pharmacologically relevant length scales, for example, those characteristic of topical drug delivery. Resulting transport parameters are salient measures of drug delivery potential, and serve as inputs to computational models of drug delivery performance. (C) 2017 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.