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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Ham, AS; Nugent, ST; Peters, JJ; Katz, DF; Shelter, CM; Dezzutti, CS; Boczar, AD; Buckheit, KW; Buckheit, RW

Published Date

  • August 2015

Published In

Volume / Issue

  • 120 /

Start / End Page

  • 153 - 164

PubMed ID

  • 26093158

Electronic International Standard Serial Number (EISSN)

  • 1872-9096

International Standard Serial Number (ISSN)

  • 0166-3542

Digital Object Identifier (DOI)

  • 10.1016/j.antiviral.2015.06.010

Language

  • eng