Full depth measurement of tenofovir transport in rectal mucosa using confocal Raman spectroscopy and optical coherence tomography.

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.

Duke Scholars

Author David F. Katz Biomedical Engineering