title: 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.affiliation: Laboratory for Pharmacotechnology and Biopharmacy, Katholieke Universiteit Leuven, Leuven, Belgium. joachim.brouwers@pharm.kuleuven.be
authors.forename: Joachim
authors.initials: J
authors.lastname: Brouwers
authors.forename: Kurt
authors.initials: K
authors.lastname: Vermeire
authors.forename: Dominique
authors.initials: D
authors.lastname: Schols
authors.forename: Patrick
authors.initials: P
authors.lastname: Augustijns
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D014622:Vaginal Creams, Foams, and Jellies / Q000737:chemistry / Q000494:pharmacology*; D014783:Viscosity
chemical_list: D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D014622:Vaginal Creams, Foams, and Jellies; D002738:Chloroquine