Two new prototype microbicide products will be developed: one based on an intravaginal ring delivery system and one on a bioresponsive (smart) gel delivery vehicle. Both products will be designed to function with the following attributes: (1) extended residence in the vagina such that their use is not coitally dependent;(2) embody either single or combination anti-HIV microbicides;and (3) have favorable acceptability by women. The smart gel will spread well initially upon insertion, and then increase in physical integrity and remain in place for at least 24 hours. The intravaginal ring will deliver a constant dose of microbicide molecules continuously over a duration of one month or greater. Three new families of active ingredients will be developed and delivered by the new vehicles. These molecules target multiple steps in the HIV infection and replication pathway and include the dual acting pyrimidinediones (inhibit virus entry and reverse transcription), ISIS 5320 (inhibits CD4-gp120 mediated attachment) and the virus inactivating NCp7 inhibitors. Collectively, these active ingredients target both cell-free and cell-associated virus. Optimal formulation strategies employing either gels or rings will be designed and implemented. The proposed work scope integrates new basic science and technology, preclinical development and exploratory clinical development. The candidate novel microbicides will be optimized for activity, stability and potency against both wild type and drug-resistant viruses. Medicinal chemistry will continue to provide compounds with enhanced antiviral properties in single or combination products. The new microbicide science and technology will fill critical gaps in the field, and foster new delivery systems that are optimized with respect to vaginal deployment and drug delivery functions. Simultaneously, current knowledge and evaluation methods for acceptability of gels and rings will be expanded, and physical attributes of these vehicles will be designed to co-optimize both behavioral acceptability and biological functionality. Product development will progress in synchrony with the new scientific understanding of HIV neutralization mechanisms, delivery system biomaterials and functionality, microbicide product pharmacokinetics and pharmacodynamics, and human perception and acceptability. The set of novel new experimental methods and pharmacokinetic and pharmacodynamic models is intended to be translatable for widespread use in the microbicide pipeline.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI077289-05
Application #
8306326
Study Section
Special Emphasis Panel (ZAI1-CCH-A (S1))
Program Officer
Turpin, Jim A
Project Start
2008-06-27
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2014-05-31
Support Year
5
Fiscal Year
2012
Total Cost
$1,080,708
Indirect Cost
$86,951
Name
Imquest Biosciences
Department
Type
DUNS #
146051664
City
Frederick
State
MD
Country
United States
Zip Code
21704
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

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