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

摘要

The DuoGel(TM) 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(TM)S containing IQP-0528, a non-nucleoside reverse transcriptase inhibitor (NNRTI), were formulated from GRAS excipients approved for vaginal and rectal administration. The DuoGel(TM)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(TM) formulations (IQB3000, IQB3001, and IQB3002) were developed at pH 6.00 and osmolality <= 400 mmol/kg. The DuoGel(TM)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 (similar to 65% reduction) and IQB3001 was removed due to increase spread resulting in leakage. IQB3002 containing IQP-0528 was defined as our lead DuoGel(TM) formulation, possessing potent activity against HIV-1 (EC50 = 10 nM). Over 12 month stability evaluations, IQB3002 maintained formulation stability. This study has identified a lead DuoGel(TM) formulation that will safely deliver IQP-0528 to prevent sexual HIV-1 transmission in the vagina and rectum. (C) 2015 Elsevier B.V. All rights reserved.