Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA.
Department of Biotechnology, Faculty of Technology, Khon Kaen University, Khon Kaen, 40002, Thailand.
Drug Deliv Transl Res. 2018 Jun;8(3):843-852. doi: 10.1007/s13346-018-0495-7.
The prophylactic activity of antiretroviral drugs applied as microbicides against sexually transmitted HIV is dependent upon their concentrations in infectable host cells. Within mucosal sites of infection (e.g., vaginal and rectal mucosa), those cells exist primarily in the stromal layer of the tissue. Traditional pharmacokinetic studies of these drugs have been challenged by poor temporal and spatial specificity. Newer techniques to measure drug concentrations, involving Raman spectroscopy, have been limited by laser penetration depth into tissue. Utilizing confocal Raman spectroscopy (RS) in conjunction with optical coherence tomography (OCT), a new lateral imaging assay enabled concentration distributions to be imaged with spatial and temporal specificity throughout the full depth of a tissue specimen. The new methodology was applied in rectal tissue using a clinical rectal gel formulation of 1% tenofovir (TFV). Confocal RS revealed diffusion-like behavior of TFV through the tissue specimen, with significant partitioning of the drug at the interface between the stromal and adipose tissue layers. This has implications for drug delivery to infectable tissue sites. The new assay can be applied to rigorously analyze microbicide transport and delineate fundamental transport parameters of the drugs (released from a variety of delivery vehicles) throughout the mucosa, thus informing microbicide product design.
抗逆转录病毒药物作为杀微生物剂预防经性传播 HIV 的活性取决于其在可感染宿主细胞中的浓度。在感染的黏膜部位（例如阴道和直肠黏膜），这些细胞主要存在于组织的基质层中。这些药物的传统药代动力学研究受到时间和空间特异性差的挑战。涉及拉曼光谱的新的药物浓度测量技术受到激光穿透组织深度的限制。利用共焦拉曼光谱（RS）结合光相干断层扫描（OCT），一种新的横向成像检测方法能够以时空特异性在组织标本的整个深度成像浓度分布。该新方法应用于直肠组织，使用 1%替诺福韦（TFV）的临床直肠凝胶制剂。共焦 RS 显示 TFV 通过组织标本的扩散样行为，药物在基质层和脂肪组织层之间的界面处有明显的分配。这对药物输送到可感染的组织部位有影响。新的检测方法可用于严格分析杀微生物剂的输送，并描述药物（从各种输送载体释放）在整个黏膜中的基本输送参数，从而为杀微生物剂产品设计提供信息。
