Assessing Deployment of Microbicidal Gels With Label-Free Optical Measurement

Duke University, Durham NC

Investigators

Abstract

[unreadable] DESCRIPTION (provided by applicant): The objective of this research is to develop a new optical technique for measuring distributions of anti-HIV microbicidal formulations applied to the lower human female reproductive tract. Promising microbicidal agents are being developed as powerful tools for combating AIDS and other sexually transmitted infections. However their proper deployment is essential for achieving prophylaxis. We propose to use low coherence interferometry (LCI) as a new high resolution, label-free method for intravaginal measurements of microbicidal gel thickness, the central characteristic of deployment. LCI uses broadband light in an interferometry scheme to achieve depth resolved reflection measurements with a resolution of a few microns. Preliminary tests show that LCI is well suited to the proposed task by demonstrating gel thickness measurements with a precision and range that meets or exceeds those of previous methods employed for this purpose. Further, because LCI can assess gel thickness without using an exogenous contrast agent, the new LCI-based method will allow for longer time studies because effects seen with fluorescent tags, such as photobleaching and dye diffusion, are avoided. Moreover, the LCI-based method will form the basis for less-expensive, more robust diagnostic systems which provide higher accuracy and easier application. Our long range goal is to contribute an incisive, robust clinical instrument for analyzing the deployment of microbicidal formulations in the female reproductive tract (and rectum). This research project will establish the feasibility of using LCI-based diagnostics for that purpose. We propose the following Specific Aims: 1. Implement prototype clinical LCI system, building on the current prototype. The current LCI system will be adapted for clinical usage based on the design in the research plan. The new prototype will be integrated with an existing fluorescence-based system currently used for clinical studies in women. 2. Analyze and compare the dual capabilities of the integrated system with co- registered laboratory in vitro tests on gel phantoms. The accuracy and precision of the two techniques will be defined. The in vitro performance of the new system will be assessed over long time scales, during which dye diffusion and gel dilution limit application of the fluorometric approach. 3. Test the integrated system in preliminary human in vivo studies. The clinical utility of the approach will be established through joint measurements of vaginal coating thickness distributions of three gels (with different properties), using both the fluorescence-based and new LCI-based techniques. Vaginal coating thickness will be mapped at short (10 min) and longer (1 hr) times after gel insertion, in a biologically relevant experimental design that achieves a range of vaginal coating distributions. Thus, complete demonstration of the proof-of-principle of using LCI for assessing deployment of microbicidal gels will be accomplished. This research project proposes to develop a new optical method for assessing the deployment of microbicidal gels in the female reproductive tract. Effective prevention of the spread of sexually transmitted diseases can be accomplished using microbicidal gels however, they must be effectively deployed. The optical tool proposed here will allow the comparison of various formulations and deployment strategies of microbicidal gels as well as enabling assessment of the amount of time that a gel effectively coats the target surface. [unreadable] [unreadable] [unreadable] [unreadable]