Abstract
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.
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Acknowledgements
We are grateful to Mrs. Jennifer Peters, Mr. Michael DeSoto, and Dr. Marcus Henderson (Duke University, Department of Biomedical Engineering) for their technical assistance and insight in this project. This work was supported by the National Institutes of Health [AI13127].
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The authors declare that they have no conflicts of interest, including no conflicting financial relationships with the National Institutes of Health, which sponsored this research under grant AI13127.
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Presnell, A.L., Chuchuen, O., Simons, M.G. et al. Full depth measurement of tenofovir transport in rectal mucosa using confocal Raman spectroscopy and optical coherence tomography. Drug Deliv. and Transl. Res. 8, 843–852 (2018). https://doi.org/10.1007/s13346-018-0495-7
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DOI: https://doi.org/10.1007/s13346-018-0495-7