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Antiviral Res. 2015 Aug;120:153-64. doi: 10.1016/j.antiviral.2015.06.010. Epub 2015 Jun 17.

The rational design and development of a dual chamber vaginal/rectal microbicide gel formulation for HIV prevention.

Author information

1
ImQuest BioSciences Inc., Frederick, MD 21704, USA. Electronic address: aham@imquestbio.com.
2
ImQuest BioSciences Inc., Frederick, MD 21704, USA.
3
Duke University, Durham, NC 27708, USA.
4
Magee-Womens Research Institute, Pittsburgh, PA 15213, USA.
5
University of Pittsburgh, Pittsburgh, PA 15213, USA; Magee-Womens Research Institute, Pittsburgh, PA 15213, USA.

Abstract

The DuoGel™ was developed for safe and effective dual chamber administration of antiretroviral drugs to reduce the high incidence of HIV transmission during receptive vaginal and anal intercourse. The DuoGel™s containing IQP-0528, a non-nucleoside reverse transcriptase inhibitor (NNRTI), were formulated from GRAS excipients approved for vaginal and rectal administration. The DuoGel™s were evaluated based upon quantitative physicochemical and biological evaluations defined by a Target Product Profile (TPP) acceptable for vaginal and rectal application. From the two primary TPP characteristics defined to accommodate safe rectal administration three DuoGel™ formulations (IQB3000, IQB3001, and IQB3002) were developed at pH 6.00 and osmolality ⩽400mmol/kg. The DuoGel™s displayed no in vitro cellular or bacterial toxicity and no loss in viability in ectocervical and colorectal tissue. IQB3000 was removed from consideration due to reduced NNRTI delivery (∼65% reduction) and IQB3001 was removed due to increase spread resulting in leakage. IQB3002 containing IQP-0528 was defined as our lead DuoGel™ formulation, possessing potent activity against HIV-1 (EC50=10nM). Over 12month stability evaluations, IQB3002 maintained formulation stability. This study has identified a lead DuoGel™ formulation that will safely deliver IQP-0528 to prevent sexual HIV-1 transmission in the vagina and rectum.

KEYWORDS:

Formulation; HIV prevention; Microbicides; Pyrimidinedione; Rectal gel; Vaginal gel

PMID:
26093158
PMCID:
PMC4492852
DOI:
10.1016/j.antiviral.2015.06.010
[Indexed for MEDLINE]
Free PMC Article

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