title: The rational design and development of a dual chamber vaginal/rectal microbicide gel formulation for HIV prevention.
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.
authors.affiliation: ImQuest BioSciences Inc., Frederick, MD 21704, USA. Electronic address: aham@imquestbio.com.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Ham
authors.affiliation: ImQuest BioSciences Inc., Frederick, MD 21704, USA.
authors.forename: Sean T
authors.initials: ST
authors.lastname: Nugent
authors.affiliation: Duke University, Durham, NC 27708, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Peters
authors.affiliation: Duke University, Durham, NC 27708, USA.
authors.forename: David F
authors.initials: DF
authors.lastname: Katz
authors.affiliation: Magee-Womens Research Institute, Pittsburgh, PA 15213, USA.
authors.forename: Cory M
authors.initials: CM
authors.lastname: Shelter
authors.affiliation: University of Pittsburgh, Pittsburgh, PA 15213, USA; Magee-Womens Research Institute, Pittsburgh, PA 15213, USA.
authors.forename: Charlene S
authors.initials: CS
authors.lastname: Dezzutti
authors.affiliation: ImQuest BioSciences Inc., Frederick, MD 21704, USA.
authors.forename: Ashlee D
authors.initials: AD
authors.lastname: Boczar
authors.affiliation: ImQuest BioSciences Inc., Frederick, MD 21704, USA.
authors.forename: Karen W
authors.initials: KW
authors.lastname: Buckheit
authors.affiliation: ImQuest BioSciences Inc., Frederick, MD 21704, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Buckheit
mesh_terms: D000282:Administration, Intravaginal; D000285:Administration, Rectal; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D018890:Chemoprevention / Q000379:methods*; D004355:Drug Stability; D005079:Excipients; D005260:Female; D005782:Gels / Q000494:pharmacology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D011744:Pyrimidinones / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D005079:Excipients; D005782:Gels; C573126:IQP-0528; D011744:Pyrimidinones
keywords: Formulation; HIV prevention; Microbicides; Pyrimidinedione; Rectal gel; Vaginal gel