Label-free analysis of tenofovir delivery to vaginal tissue using co-registered confocal Raman spectroscopy and optical coherence tomography.
Oranat ChuchuenJason R MaherMarcus H HendersonMichael DesotoLisa C RohanAdam WaxDavid F KatzPublished in: PloS one (2017)
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.
Keyphrases
- raman spectroscopy
- optical coherence tomography
- drug delivery
- antiretroviral therapy
- label free
- high throughput
- wound healing
- diabetic retinopathy
- magnetic resonance
- hyaluronic acid
- hiv infected
- hiv positive
- bone marrow
- drug induced
- cancer therapy
- emergency department
- computed tomography
- machine learning
- adverse drug
- diffusion weighted imaging
- south africa
- ulcerative colitis