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

Abstract

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 IC(50)-values of chloroquine (ca. 6 microg/ml). The gels were clear and homogeneous and displayed an 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 dose-dependent anti-HIV-1 activity in vitro (mean IC(50) 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.

• Authors: Joachim Brouwers, Kurt Vermeire, Dominique Schols, Patrick Augustijns
• Journal: Virology (Virology) Vol. 378 Issue 2 Pg. 306-10 (Sep 01 2008) ISSN: 1096-0341 [Electronic] United States
• PMID: 18606432 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Anti-Infective Agents
• Vaginal Creams, Foams, and Jellies
• Chloroquine

Topics

• Anti-HIV Agents (pharmacology)
• Anti-Infective Agents (pharmacology)
• Cell Line
• Chloroquine (pharmacology)
• Dose-Response Relationship, Drug
• Drug Stability
• HIV Infections (prevention & control)
• HIV-1 (drug effects)
• Humans
• Hydrogen-Ion Concentration
• Inhibitory Concentration 50
• Vaginal Creams, Foams, and Jellies (chemistry, pharmacology)
• Viscosity