Development and in vitro evaluation of chloroquine gels as microbicides against HIV-1 infection

The potential success of a microbicide candidate in resource-poor Countries will depend to a large extent on its availability and cost. Chloroquine is an inexpensive antimalarial drug that also exerts anti-HIV activity. The Purpose of this study was to develop and characterize a vaginal formulation for chloroquine with preservation of its anti-HIV-1 activity. Gels containing the nonionic polymer hydroxyethyl cellulose were loaded with concentrations of the diphosphate salt of chloroquine (0.3-30 mg/g), that were 10(2) to 10(4) fold higher than typical in vitro anti-HIV-1 IC50-values of chloroquine (ca. 6 mu g/ml). The gels were clear and homogeneous and displayed all osmolality of 300 mOsm/kg, a pH of 4.6 and a viscosity of 1.4 Pa s. Gel characteristics were preserved for at least 3 months at 40 degrees C and 75% relative humidity. Importantly, the chloroquine gels exerted a close-dependent anti-HIV-1 activity in vitro (mean IC50 from 23 to 0.4 mg gel/ml) and the intrinsic activity of chloroquine was not affected by formulation factors. The in vitro efficacy of the chloroquine gel formulations warrants further testing of this drug as an anti-HIV-1 microbicide candidate. (C) 2008 Elsevier Inc. All rights reserved.