The proposed Project includes a complex interplay of both microbicide product development with single agent and combination microbicide products uniquely delivered to both the vaginal and rectal compartments, as well as microbicide science advancement in which the active microbicides will be utilized as tools to better understand microbicide dosing, pharmacokinetics and pharmacodynamics in explants, nonhuman primates and humans, and acceptability/user perception. The product development components consist of the dual acting entry and nonnucleoside reverse transcriptase inhibitor IQP-0528 (a pyrimidinedione with subnanomolar activity against clinical strains of HIV-1) used alone and in combination with tenofovir in dual compartment (DuoGels) gels and smart suppository/pessary (Smart Suppository) delivery vehicles that will enable dosing in both vaginal and rectal compartments. We believe the potential advancements in product development (new microbicide agents, combination products, long lasting delivery technology, dual compartment delivery technology) and microbicide science (dosing estimation, pharmacokinetics, pharmacodynamics, in vitro, ex vivo, and in vivo modeling, effects of seminal and vaginal fluids, acceptability testing methods) make this proposal both inherently novel and important to the field of microbicide science in regard to the development of the next generation of microbicide products. In whole, the Project also provides for the development of novel PK/PD assays, novel single and combination products, novel delivery strategies, and novel microbicide development advancements to better understand and prioritize the development and use of microbicide products. The Administrative Core will play a critical and essential role in ensuring the smooth integration of the various Projects and Cores included in this cooperative agreement research program. The successful performance of this Project requires a high degree of communication and interaction between the various Projects, the Cores, and the Corporate Partner. The Administrative Core will be responsible for managing and enhancing this constructive and synergistic interplay between the participating scientific groups.

Public Health Relevance

The Administrative Core is essential for assuring that project objectives required to develop new and novel microbicide products are met in a timely and cost effective manner. The Administrative Core will coordinate the activities of the Scientific Advisory Panel and arrange for the annual program evaluation by these external reviewers to assure efficient and scientifically robust product development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI101961-03
Application #
8699503
Study Section
Special Emphasis Panel (ZAI1-ESB-A)
Project Start
Project End
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
3
Fiscal Year
2014
Total Cost
$273,659
Indirect Cost
$36,717
Name
Imquest Biosciences
Department
Type
DUNS #
146051664
City
Frederick
State
MD
Country
United States
Zip Code
21704
Weld, Ethel D; Hiruy, Hiwot; Guthrie, Kate Morrow et al. (2017) A Comparative Pre-Phase I Study of the Impact of Gel Vehicle Volume on Distal Colon Distribution, User Experience, and Acceptability. AIDS Res Hum Retroviruses 33:440-447
Ham, Anthony S; Buckheit Jr, Robert W (2017) Designing and developing suppository formulations for anti-HIV drug delivery. Ther Deliv 8:805-817
Gao, Y; Yuan, A; Chuchuen, O et al. (2015) Vaginal deployment and tenofovir delivery by microbicide gels. Drug Deliv Transl Res 5:279-94
Ham, Anthony S; Nugent, Sean T; Peters, Jennifer J et al. (2015) The rational design and development of a dual chamber vaginal/rectal microbicide gel formulation for HIV prevention. Antiviral Res 120:153-64
Katz, David F; Yuan, Andrew; Gao, Yajing (2015) Vaginal drug distribution modeling. Adv Drug Deliv Rev 92:2-13
Pereira, Lara E; Mesquita, Pedro M M; Ham, Anthony et al. (2015) Pharmacokinetic and Pharmacodynamic Evaluation following Vaginal Application of IQB3002, a Dual-Chamber Microbicide Gel Containing the Nonnucleoside Reverse Transcriptase Inhibitor IQP-0528 in Rhesus Macaques. Antimicrob Agents Chemother 60:1393-400