This application will bring forward novel topical microbicide products that will be formulated using pH and thermo sensitive gels and intravaginal rings. To ensure that these products in their formulations are safe and effective, the Explant Core will evaluate them for toxicity to cervcial explant tissues and efficacy against HIV- 1 infection. Over years 1 through 3, 10 gels and 10 ring formulations (20 total) will be evaluated yearly. Four combination products (e.g. two product candidates in gels or one product in a gel and one product in a ring) will be evaluated in year 2 and 3. The unique aspects of this Core will be studying the timing issues of product application and whether the proudct(s) is effective if used several hours prior to HIV-1 exposure to test for coital independance. The products that are the least toxic and most effective will be further refined for development. Over years 4 and 5, this refined evaluation will include use of product in the cervical explant cultures in the presence of seminal plasma. Because seminal plasma will influence the infectivity of HIV-1, it is necessary to include these studies. To ensure that the products that are being developed are safe, the Explant Core in conjunction with the Virology Core will evaluate cervicovaginal lavages obtained from women using the placebo formulations of gels to measure innate immune factors and intrinsic anti-microbial activity. The work provided by this Core will serve Projects 1 (Novel Delivery Systems) and 2 (Microbicide Performance Analysis). The findings from this Core will be used by Project 3 to ensure only those products are the safest are used in women. Collectively, this Core will evaluate new product formulations for safety and efficacy against HIV-1 using a state-of-the-art cervical explant culture system. The findings from this Core will help to quickly evaluate new products to move the microbicide product pipeline forward. Relevance: Microbicides are being developed to prevent the spread of HIV-1. The Explant Core will provide the investigators of this application information regarding microbicide safety and the ability to protect against HIV-1 infection using human tissue that would normally be discarded after surgery. The human tissue used by these scientists provide us the best bridge between the laboratory and the clinic to study microbicides.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-CCH-A)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Imquest Biosciences
United States
Zip Code
Morrow Guthrie, Kate; Vargas, Sara; Shaw, Julia G et al. (2015) The Promise of Intravaginal Rings for Prevention: User Perceptions of Biomechanical Properties and Implications for Prevention Product Development. PLoS One 10:e0145642
Rosen, Rochelle K; van den Berg, Jacob J; Vargas, Sara E et al. (2015) Meaning-making matters in product design: users' sensory perceptions and experience evaluations of long-acting vaginal gels and intravaginal rings. Contraception 92:596-601
Ugaonkar, Shweta R; Clark, Justin T; English, Lexie B et al. (2015) An Intravaginal Ring for the Simultaneous Delivery of an HIV-1 Maturation Inhibitor and Reverse-Transcriptase Inhibitor for Prophylaxis of HIV Transmission. J Pharm Sci 104:3426-39
Katz, David F; Yuan, Andrew; Gao, Yajing (2015) Vaginal drug distribution modeling. Adv Drug Deliv Rev 92:2-13
Gao, Y; Yuan, A; Chuchuen, O et al. (2015) Vaginal deployment and tenofovir delivery by microbicide gels. Drug Deliv Transl Res 5:279-94
van den Berg, Jacob J; Rosen, Rochelle K; Bregman, Dana E et al. (2014) ""Set it and forget it"": women's perceptions and opinions of long-acting topical vaginal gels. AIDS Behav 18:862-70
Tolley, Elizabeth E; Morrow, Kathleen M; Owen, Derek H (2013) Designing a multipurpose technology for acceptability and adherence. Antiviral Res 100 Suppl:S54-9
Rastogi, Rachna; Teller, Ryan S; Mesquita, Pedro M M et al. (2013) Osmotic pump tablets for delivery of antiretrovirals to the vaginal mucosa. Antiviral Res 100:255-8
Drake, Tyler K; Shah, Tejen; Peters, Jennifer J et al. (2013) Measuring dilution of microbicide gels with optical imaging. PLoS One 8:e82213
Dezzutti, Charlene S; Shetler, Cory; Mahalingam, Alamelu et al. (2012) Safety and efficacy of tenofovir/IQP-0528 combination gels - a dual compartment microbicide for HIV-1 prevention. Antiviral Res 96:221-5

Showing the most recent 10 out of 23 publications