Label-free analysis of tenofovir delivery to vaginal tissue using co-registered confocal Raman spectroscopy and optical coherence tomography.
Label-free analysis of tenofovir delivery to vaginal tissue using co-registered confocal Raman spectroscopy and optical coherence tomography.
复制标题
DOI：
10.1371/journal.pone.0185633
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Katz DF
中科院分区：
文献类型：
--
作者：
Chuchuen O;Maher JR;Henderson MH;Desoto M;Rohan LC;Wax A;Katz DF
阴道施用的杀微生物剂产品为预防艾滋病毒的性传播提供了一种由女性控制的战略。杀微生物剂的迁移过程对其运作至关重要，显然需要更好地了解这些过程。为此，我们开发了一种测定方法，用于分析在与凝胶载体接触期间，极化阴道粘膜组织的上皮层和基质层内杀微生物剂分子的质量转运速率。该分析利用了一个新的扩散室安装在一个定制的仪器，结合共焦拉曼光谱和光学相干断层扫描。这测量了上皮和基质内的深度分辨杀微生物剂浓度分布。替诺福韦凝胶的数据与房室扩散模型拟合，以获得基本的传输特性：分子扩散和分配系数在不同的隔室。上皮和间质中的扩散系数分别计算为6.10 ± 2.12 x 10−8和4.52 ± 1.86 x 10−7 cm 2/sec。上皮与凝胶、基质与上皮的分配系数分别为0.53 ± 0.15和1.17 ± 0.16。这些药物转运参数在控制不同药物和凝胶载体系统的药物递送性能方面是突出的。它们可用于在产品设计、开发和筛选过程中对比药物和载体。它们是预测凝胶药代动力学性能的确定性转运模型的关键输入，可以指导产品的改进设计和给药方案的优化。
Vaginally applied microbicide products offer a female-controlled strategy for preventing sexual transmission of HIV. Microbicide transport processes are central to their functioning, and there is a clear need for a better understanding of them. To contribute to that end, we developed an assay to analyze mass transport rates of microbicide molecules within the epithelial and stromal layers of polarized vaginal mucosal tissue during contact with a gel vehicle. The assay utilizes a new diffusion chamber mounted in a custom instrument that combines confocal Raman spectroscopy and optical coherence tomography. This measures depth-resolved microbicide concentration distributions within epithelium and stroma. Data for a tenofovir gel were fitted with a compartmental diffusion model to obtain fundamental transport properties: the molecular diffusion and partition coefficients in different compartments. Diffusion coefficients in epithelium and stroma were computed to be 6.10 ± 2.12 x 10−8 and 4.52 ± 1.86 x 10−7 cm2/sec, respectively. The partition coefficients between epithelium and gel and between stroma and epithelium were found to be 0.53 ± 0.15 and 1.17 ± 0.16, respectively. These drug transport parameters are salient in governing the drug delivery performance of different drug and gel vehicle systems. They can be used to contrast drugs and vehicles during product design, development and screening. They are critical inputs to deterministic transport models that predict the gels’ pharmacokinetic performance, which can guide improved design of products and optimization of their dosing regimens.
登录
查看更多内容
影响因子：
3.7
作者：
McGowan I;Hoesley C;Cranston RD;Andrew P;Janocko L;Dai JY;Carballo-Dieguez A;Ayudhya RK;Piper J;Hladik F;Mayer K
通讯作者：
Mayer K
影响因子：
7.4
作者：
HAALAND, DM;THOMAS, EV
通讯作者：
THOMAS, EV
影响因子：
3.8
作者：
Chuchuen, Oranat;Maher, Jason R.;Katz, David F.
通讯作者：
Katz, David F.
影响因子：
7.6
作者：
Lai, Bonnie E.;Geonnotti, Anthony R.;Katz, David F.
通讯作者：
Katz, David F.
影响因子：
3.7
作者：
Hendrix CW;Chen BA;Guddera V;Hoesley C;Justman J;Nakabiito C;Salata R;Soto-Torres L;Patterson K;Minnis AM;Gandham S;Gomez K;Richardson BA;Bumpus NN
通讯作者：
Bumpus NN