A Pilot Study Measuring the Distribution and Permeability of a Vaginal HIV Microbicide Gel Vehicle Using Magnetic Resonance Imaging, Single Photon Emission Computed Tomography/Computed Tomography, and a Radiolabeled Small Molecule.
Publication/Presentation Date
11-1-2015
Abstract
Vaginal microbicide gels containing tenofovir have proven effective in HIV prevention, offering the advantage of reduced systemic toxicity. We studied the vaginal distribution and effect on mucosal permeability of a gel vehicle. Six premenopausal women were enrolled. In Phase 1, a spreading gel containing (99m)technetium-DTPA ((99m)Tc) radiolabel and gadolinium contrast for magnetic resonance imaging (MRI) was dosed intravaginally. MRI was obtained at 0.5, 4, and 24 h, and single photon emission computed tomography with conventional computed tomography (SPECT/CT) at 1.5, 5, and 25 h postdosing. Pads and tissues were measured for activity to determine gel loss. In Phase 2, nonoxynol-9 (N-9), containing (99m)Tc-DTPA, was dosed as a permeability control; permeability was measured in blood and urine for both phases. SPECT/CT showed the distribution of spreading gel throughout the vagina with the highest concentration of radiosignal in the fornices and ectocervix; signal intensity diminished over 25 h. MRI showed the greatest signal accumulation in the fornices, most notably 1-4 h postdosing. The median (interquartile range) isotope signal loss from the vagina through 6 h was 29.1% (15.8-39.9%). Mucosal permeability to (99m)Tc-DTPA following spreading gel was negligible, in contrast to N-9, with detectable radiosignal in plasma, peaking at 8 h (5-12). Following spreading gel dosing, 0.004% (0.001-2.04%) of the radiosignal accumulated in urine over 12 h compared to 8.31% (7.07-11.01%) with N-9, (p=0.043). Spreading gel distributed variably throughout the vagina, persisting for 24 h, with signal concentrating in the fornices and ectocervix. The spreading gel had no significant effect on vaginal mucosal permeability.
Volume
31
Issue
11
First Page
1109
Last Page
1115
ISSN
1931-8405
Published In/Presented At
Fuchs, E. J., Schwartz, J. L., Friend, D. R., Coleman, J. S., & Hendrix, C. W. (2015). A Pilot Study Measuring the Distribution and Permeability of a Vaginal HIV Microbicide Gel Vehicle Using Magnetic Resonance Imaging, Single Photon Emission Computed Tomography/Computed Tomography, and a Radiolabeled Small Molecule. AIDS research and human retroviruses, 31(11), 1109–1115. https://doi.org/10.1089/AID.2015.0054
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
26077739
Department(s)
Administration and Leadership
Document Type
Article